Publications by authors named "Martine Laville"

151 Publications

Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women.

JCI Insight 2021 Apr 15. Epub 2021 Apr 15.

Univ Lyon, CarMeN Laboratory, INSERM, INRAE, Université Claude Bernard Lyon 1, Pierre-Bénite, France.

Background: High circulating levels of ceramides (Cer) and sphingomyelins (SM) have been associated with cardiometabolic diseases. The consumption of whole-fat dairy products, which naturally contain such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown. We investigated how milk PL supplementation impacts circulating and intestinal SM and Cer composition in association with improvement of cardiovascular markers.

Methods: In a 4 week-randomized double-blind controlled study, 58 postmenopausal women consumed daily a cream cheese containing 0, 3 or 5 g of milk PL. Postprandial metabolic explorations were performed before and after the supplementation. SM and Cer species were analyzed in serum, intestine-derived chylomicrons and feces. The ileal content of 4 ileostomy patients was also explored after milk PL intake in a crossover double-blind study.

Results: Milk PL consumption decreased serum atherogenic C24:1 Cer (Pgroup = 0.033), C16:1 (Pgroup = 0.007) and C18:1 (Pgroup = 0.003) SM species. Changes in serum C16+18 SM species were positively correlated with the reduction of total cholesterol (r = 0.706, P < 0.001), LDL-C (r = 0.666, P < 0.001) and ApoB (r = 0.705, P < 0.001). Milk PL decreased the concentration in chylomicrons of total SM (Pgroup < 0.0001) and of C24:1 Cer (Pgroup = 0.001). Saturated SM and Cer species, which are also the major species found in milk PL-enriched cheeses, increased in ileal efflux and feces. There was a marked increase in total fecal Cer after milk PL supplementation (Pgroup = 0.0002). Milk PL also modulated the abundance of some specific SM and Cer species in ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.

Conclusion: These data demonstrate that milk PL supplementation decreases atherogenic SM and Cer species associated with an improvement of cardiovascular risk markers. Our findings bring new insights on sphingolipid metabolism in the gastrointestinal tract, especially Cer as such signaling molecules potentially participating in the beneficial effect of milk PL. ClinicalTrials.gov, NCT02099032, NCT02146339.FUNDINGS. Agence Nationale de la Recherche, ANR-11-ALID-007-01; Regional Hospital Clinical Research Program (PHRCI-2014: VALOBAB, n°14-007); French Dairy Interbranch Organization (CNIEL); Groupe Lipides et Nutrition (GLN 2018-11-07), Hospices Civils de Lyon as sponsor.
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http://dx.doi.org/10.1172/jci.insight.146161DOI Listing
April 2021

Serum IRAP, a Novel Direct Biomarker of Prediabetes and Type 2 Diabetes?

Front Mol Biosci 2020 16;7:596141. Epub 2021 Feb 16.

Population Health Department, Nutrition and Health Research Group, Luxembourg Institute of Health, Luxembourg, Luxembourg.

Insulin resistance (IR), currently called prediabetes (PD), affects more than half of the adult population worldwide. Type 2 diabetes (T2D), which often follows in the absence of treatment, affects more than 475 million people and represents 10-20% of the health budget in industrialized countries. A preventive public health policy is urgently needed in order to stop this constantly progressing epidemic. Indeed, early management of prediabetes does not only strongly reduce its evolution toward T2D but also strongly reduces the appearance of cardiovascular comorbidity as well as that of associated cancers. There is however currently no simple and reliable test available for the diagnosis or screening of prediabetes and it is generally estimated that 20-60% of diabetics are not diagnosed. We therefore developed an ELISA for the quantitative determination of serum Insulin-Regulated AminoPeptidase (IRAP). IRAP is associated with and translocated in a stoechiometric fashion to the plasma membrane together with GLUT4 in response to insulin in skeletal muscle and adipose tissue which are the two major glucose storage sites. Its extracellular domain (IRAPs) is subsequently cleaved and secreted in the blood stream. In T2D, IRAP translocation in response to insulin is strongly decreased. Our patented sandwich ELISA is highly sensitive (≥10.000-fold "normal" fasting concentrations) and specific, robust and very cost-effective. Dispersion of fasting plasma concentration values in a healthy population is very low (101.4 ± 15.9 μg/ml) as compared to those of insulin (21-181 pmol/l) and C-peptide (0.4-1.7 nmol/l). Results of pilot studies indicate a clear correlation between IRAPs levels and insulin sensitivity. We therefore think that plasma IRAPs may be a direct marker of insulin sensitivity and that the quantitative determination of its plasma levels should allow large-scale screening of populations at risk for PD and T2D, thereby allow the enforcement of a preventive health policy aiming at efficiently reducing this epidemic.
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http://dx.doi.org/10.3389/fmolb.2020.596141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921167PMC
February 2021

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial.

Eur J Nutr 2021 Feb 5. Epub 2021 Feb 5.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium.

Purpose: Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation in obese patients.

Methods: Microbiota (16S rRNA sequencing), long- and short-chain fatty acids (LCFA, SCFA), bile acids, zonulin, and calprotectin were analyzed in fecal samples obtained from obese patients included in a randomized, placebo-controlled trial. Participants received either 16 g/d native inulin (prebiotic n = 12) versus maltodextrin (placebo n = 12), coupled to dietary advice to consume inulin-rich versus inulin-poor vegetables for 3 months, in addition to dietary caloric restriction.

Results: Both placebo and prebiotic interventions lowered energy and protein intake. A substantial increase in Bifidobacterium was detected after ITF treatment (q = 0.049) supporting our recent data obtained in a larger cohort. Interestingly, fecal calprotectin, a marker of gut inflammation, was reduced upon ITF treatment. Both prebiotic and placebo interventions increased the ratio of tauro-conjugated/free bile acids in feces. Prebiotic treatment did not significantly modify fecal SCFA content but it increased fecal rumenic acid, a conjugated linoleic acid (cis-9, trans-11 CLA) with immunomodulatory properties, that correlated notably to the expansion of Bifidobacterium (p = 0.031; r = 0.052).

Conclusions: Our study demonstrates that ITF-prebiotic intake during 3 months decreases a fecal marker of intestinal inflammation in obese patients. Our data point to a potential contribution of microbial lipid-derived metabolites in gastro-intestinal dysfunction related to obesity. CLINICALTRIALS.

Gov Identifier: NCT03852069 (February 22, 2019 retrospectively, registered).
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http://dx.doi.org/10.1007/s00394-021-02484-5DOI Listing
February 2021

Noninvasive monitoring of fibre fermentation in healthy volunteers by analyzing breath volatile metabolites: lessons from the FiberTAG intervention study.

Gut Microbes 2021 Jan-Dec;13(1):1-16

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain , Brussels, Belgium.

The fermentation of dietary fibre (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastrointestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chitin-glucan (CG), an insoluble DF previously shown to be fermented into short-chain fatty acids (SCFA) by the human microbiota in vitro. Maltodextrin (4.5 g at day 0) or CG (4.5 g at day 2) were added to a standardized breakfast in fasting healthy volunteers (n = 15). BVM were measured using selected ion flow tube mass spectrometry (SIFT-MS) throughout the day. A single ingestion of 4.5 g CG did not induce significant gastrointestinal discomfort. Untargeted metabolomics analysis of breath highlighted that 13 MS-fragments (among 408 obtained from ionizations of breath) discriminated CG versus maltodextrin acute intake in the posprandial state. The targeted analysis revealed that CG increased exhaled butyrate and 5 other BVM - including the microbial metabolites 2,3-butanedione and 3-hydroxybutanone - with a peak observed 6 h after CG intake. Correlation analyses with fecal microbiota (Illumina 16S rRNA sequencing) spotlighted as a potential genus responsible for the presence of butyric acid, triethylamine and 3-hydroxybutanone in the breath. In conclusion, measuring BMV in the breath reveals the microbial signature of the fermentation of DF after a single ingestion. This protocol allows to analyze the time-course of released bioactive metabolites that could be proposed as new biomarkers of DF fermentation, potentially linked to their biological properties. Trial registration: Clinical Trials NCT03494491. Registered 11 April 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03494491.
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http://dx.doi.org/10.1080/19490976.2020.1862028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833774PMC
January 2021

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study.

Nutr Metab Cardiovasc Dis 2021 01 25;31(1):237-246. Epub 2020 Aug 25.

Centre de Recherche en Nutrition Humaine Rhône-Alpes, Univ-Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, F-CRIN/FORCE Network, 69310, Pierre Bénite, France. Electronic address:

Background And Aims: In type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients' diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.

Methods And Results: For this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System. Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140-180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.

Conclusion: One week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control. REGISTRATION NUMBER: in clinicaltrials.gov: NCT03289494.
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http://dx.doi.org/10.1016/j.numecd.2020.08.010DOI Listing
January 2021

Development of a Repertoire and a Food Frequency Questionnaire for Estimating Dietary Fiber Intake Considering Prebiotics: Input from the FiberTAG Project.

Nutrients 2020 Sep 15;12(9). Epub 2020 Sep 15.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, 1200 Sint-Lambrechts-Woluwe, Belgium.

Most official food composition tables and food questionnaires do not provide enough data to assess fermentable dietary fibers (DF) that can exert a health effect through their interaction with the gut microbiota. The aim of this study was to develop a database and a food frequency questionnaire (FFQ) allowing detailed DF intake estimation including prebiotic (oligo)saccharides. A repertoire of DF detailing total, soluble DF, insoluble DF and prebiotic (oligo)saccharides (inulin-type fructans, fructo-oligosaccharides and galacto-oligosaccharides) in food products consumed in Europe has been established. A 12 month FFQ was developed and submitted to 15 healthy volunteers from the FiberTAG study. Our data report a total DF intake of 38 g/day in the tested population. Fructan and fructo-oligosaccharides intake, linked notably to condiments (garlic and onions) ingestion, reached 5 and 2 g/day, respectively, galacto-oligosaccharides intake level being lower (1 g/day). We conclude that the FiberTAG repertoire and FFQ are major tools for the evaluation of the total amount of DF including prebiotics. Their use can be helpful in intervention or observational studies devoted to analyze microbiota-nutrient interactions in different pathological contexts, as well as to revisit DF intake recommendations as part of healthy lifestyles considering specific DF.
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http://dx.doi.org/10.3390/nu12092824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551723PMC
September 2020

Metabolite profiling reveals the interaction of chitin-glucan with the gut microbiota.

Gut Microbes 2020 11;12(1):1810530

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université Catholique de Louvain , Brussels, Belgium.

Dietary fibers are considered beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. In this context, chitin-glucan (CG) improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota has never been evaluated in humans. This study explores the effect of a 3-week intervention with CG supplementation in healthy individuals on gut microbiota composition and bacterial metabolites. CG was given to healthy volunteers (n = 15) for three weeks as a supplement (4.5 g/day). Food diary, visual analog and Bristol stool form scales and a "quality of life" survey were analyzed. Among gut microbiota-derived metabolites, bile acids (BA), long- and short-chain fatty acids (LCFA, SCFA) profiling were assessed in stool samples. The gut microbiota (primary outcome) was analyzed by Illumina sequencing. A 3-week supplementation with CG is well tolerated in healthy humans. CG induces specific changes in the gut microbiota composition, with and genera showing the strongest regulation. In addition, CG increased bacterial metabolites in feces including butyric, iso-valeric, caproic and vaccenic acids. No major changes were observed for the fecal BA profile following CG intervention. In summary, our work reveals new potential bacterial genera and gut microbiota-derived metabolites characterizing the interaction between an insoluble dietary fiber -CG- and the gut microbiota.
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http://dx.doi.org/10.1080/19490976.2020.1810530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524357PMC
November 2020

Gut microbiota modulation with long-chain corn bran arabinoxylan in adults with overweight and obesity is linked to an individualized temporal increase in fecal propionate.

Microbiome 2020 08 19;8(1):118. Epub 2020 Aug 19.

Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada.

Background: Variability in the health effects of dietary fiber might arise from inter-individual differences in the gut microbiota's ability to ferment these substrates into beneficial metabolites. Our understanding of what drives this individuality is vastly incomplete and will require an ecological perspective as microbiomes function as complex inter-connected communities. Here, we performed a parallel two-arm, exploratory randomized controlled trial in 31 adults with overweight and class-I obesity to characterize the effects of long-chain, complex arabinoxylan (n = 15) at high supplementation doses (female: 25 g/day; male: 35 g/day) on gut microbiota composition and short-chain fatty acid production as compared to microcrystalline cellulose (n = 16, non-fermentable control), and integrated the findings using an ecological framework.

Results: Arabinoxylan resulted in a global shift in fecal bacterial community composition, reduced α-diversity, and the promotion of specific taxa, including operational taxonomic units related to Bifidobacterium longum, Blautia obeum, and Prevotella copri. Arabinoxylan further increased fecal propionate concentrations (p = 0.012, Friedman's test), an effect that showed two distinct groupings of temporal responses in participants. The two groups showed differences in compositional shifts of the microbiota (p ≤ 0.025, PERMANOVA), and multiple linear regression (MLR) analyses revealed that the propionate response was predictable through shifts and, to a lesser degree, baseline composition of the microbiota. Principal components (PCs) derived from community data were better predictors in MLR models as compared to single taxa, indicating that arabinoxylan fermentation is the result of multi-species interactions within microbiomes.

Conclusion: This study showed that long-chain arabinoxylan modulates both microbiota composition and the output of health-relevant SCFAs, providing information for a more targeted application of this fiber. Variation in propionate production was linked to both compositional shifts and baseline composition, with PCs derived from shifts of the global microbial community showing the strongest associations. These findings constitute a proof-of-concept for the merit of an ecological framework that considers features of the wider gut microbial community for the prediction of metabolic outcomes of dietary fiber fermentation. This provides a basis to personalize the use of dietary fiber in nutritional application and to stratify human populations by relevant gut microbiota features to account for the inconsistent health effects in human intervention studies.

Trial Registration: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00887-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439537PMC
August 2020

Design and Validation of a Diet Rich in Slowly Digestible Starch for Type 2 Diabetic Patients for Significant Improvement in Glycemic Profile.

Nutrients 2020 Aug 11;12(8). Epub 2020 Aug 11.

Nutrition Research, Mondelēz International, 91400 Saclay, France.

This study aimed at designing a-diet high in slowly digestible starch (SDS) by carefully selecting high-SDS starchy products and to validate its implementation, acceptance, and impact on the postprandial glycemic response in patients with type 2 diabetes (T2D). Starchy products were screened and classified as being either high (high-SDS) or low (low-SDS) in SDS (in vitro SDS method). A randomized controlled cross-over pilot study was performed: Eight patients with T2D consumed randomly a high-SDS or a low-SDS diet for one week each, while their glycemic profile was monitored for 6 days. Based on 250 food product SDS analyses and dietary recommendations for patients with T2D, the high-SDS and low-SDS diets were designed. The high-SDS diet significantly increased SDS intake and the SDS/carbohydrates proportion compared to the low-SDS diet (61.6 vs. 11.6 g/day and 30% vs. 6%; < 0.0001, respectively). Increasing the SDS/carbohydrate proportion to 50% of the meal was significantly correlated with a 12% decrease in tAUC0-120 min and a 14% decrease in the glycemic peak value ( < 0.001 for both). A high-SDS diet can be easily designed by carefully selecting commercial starchy products and providing relevant recommendations for T2D to improve their glycemic profile.
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http://dx.doi.org/10.3390/nu12082404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468810PMC
August 2020

A series of severe neurologic complications after bariatric surgery in France: the NEUROBAR Study.

Surg Obes Relat Dis 2020 Oct 12;16(10):1429-1435. Epub 2020 Jun 12.

Service d'Endocrinologie, Diabétologie, Nutrition, CHU Grenoble Alpes, Grenoble, France. Electronic address:

Background: Neurologic complications after bariatric surgery are rare, but can have dramatic consequences. Little data are available on this topic.

Objectives: The aim of the Neurologic complications after BARiatric surgery (NEUROBAR) study was to define, which factors (anthropometric, nutritional, surgical, etc.) were frequently associated with neurologic complications after bariatric surgery.

Settings: Data were collected by the French Centers of Obesity Care Management hosted in University Hospitals.

Methods: An online standardized questionnaire was designed and submitted to the 37 French Centers of Obesity Management. This questionnaire included items about patient characteristics, bariatric surgery, neurologic complications, nutritional status, and management. Patients were retrospectively included from January 2010 to November 2018.

Results: Thirteen centers included 38 patients (34 females and 4 males) with neurologic complications after bariatric surgery. The 2 main bariatric procedures were gastric bypass and sleeve gastrectomy. More than half of the patients with neurologic complications had a surgical complication after bariatric surgery (53%) and gastrointestinal symptoms, including vomiting (53%). Vitamin B deficiencies were frequent (74%) including at least 47% of cases with deficiency in Vitamin B1.

Conclusion: Early identification of patients with surgical complications and gastrointestinal symptoms after bariatric surgery could help prevent neurologic complications related to nutritional deficiencies.
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http://dx.doi.org/10.1016/j.soard.2020.05.031DOI Listing
October 2020

Postprandial Endotoxin Transporters LBP and sCD14 Differ in Obese vs. Overweight and Normal Weight Men during Fat-Rich Meal Digestion.

Nutrients 2020 Jun 18;12(6). Epub 2020 Jun 18.

Univ Lyon, CarMeN Laboratory, INRAE, UMR1397, INSERM, UMR1060, Université Claude Bernard Lyon 1, 69310 Pierre Bénite, France.

Circulating levels of lipopolysaccharide-binding protein (LBP) and soluble cluster of differentiation 14 (sCD14) are recognized as clinical markers of endotoxemia. In obese men, postprandial endotoxemia is modulated by the amount of fat ingested, being higher compared to normal-weight (NW) subjects. Relative variations of LBP/sCD14 ratio in response to overfeeding are also considered important in the inflammation set-up, as measured through IL-6 concentration. We tested the hypothesis that postprandial LBP and sCD14 circulating concentrations differed in obese vs. overweight and NW men after a fat-rich meal. We thus analyzed the postprandial kinetics of LBP and sCD14 in the context of two clinical trials involving postprandial tests in normal-, over-weight and obese men. In the first clinical trial eight NW and 8 obese men ingested breakfasts containing 10 vs. 40 g of fat. In the second clinical trial, 18 healthy men were overfed during 8 weeks. sCD14, LBP and Il-6 were measured in all subjects during 5 h after test meal. Obese men presented a higher fasting and postprandial LBP concentration in plasma than NW men regardless of fat load, while postprandial sCD14 was similar in both groups. Irrespective of the overfeeding treatment, we observed postprandial increase of sCD14 and decrease of LBP before and after OF. In obese individuals receiving a 10 g fat load, whereas IL-6 increased 5h after meal, LBP and sCD14 did not increase. No direct association between the postprandial kinetics of endotoxemia markers sCD14 and LBP and of inflammation in obese men was observed in this study.
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http://dx.doi.org/10.3390/nu12061820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353369PMC
June 2020

COVID-19: A Lever for the Recognition of Obesity as a Disease? The French Experience.

Obesity (Silver Spring) 2020 09 7;28(9):1584-1585. Epub 2020 Aug 7.

Specialized Obesity Center and Endocrinology, Diabetology, Nutrition dept, Brabois Hospital, CHRU of Nancy, F-CRIN/FORCE Network, Vandoeuvre-Les-Nancy, France.

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http://dx.doi.org/10.1002/oby.22924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300927PMC
September 2020

International consensus on the diagnosis and management of dumping syndrome.

Nat Rev Endocrinol 2020 08 26;16(8):448-466. Epub 2020 May 26.

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Catholic University of Leuven, Leuven, Belgium.

Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose.
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http://dx.doi.org/10.1038/s41574-020-0357-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351708PMC
August 2020

Prevalence of obesity among adult inpatients with COVID-19 in France.

Lancet Diabetes Endocrinol 2020 07 18;8(7):562-564. Epub 2020 May 18.

CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Hôpital Lyon Sud, Pierre-Bénite 69495, France; Hospices Civils de Lyon, Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, Pierre-Bénite 69495, France; COVID-O-HCL Consortium, Hospices Civils de Lyon, Lyon, France.

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http://dx.doi.org/10.1016/S2213-8587(20)30160-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234780PMC
July 2020

Obesity is Associated with Severe Forms of COVID-19.

Obesity (Silver Spring) 2020 07 21;28(7):1175. Epub 2020 May 21.

CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France.

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http://dx.doi.org/10.1002/oby.22842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264509PMC
July 2020

Association of Dietary Patterns Derived Using Reduced-Rank Regression With Subclinical Cardiovascular Damage According to Generation and Sex in the STANISLAS Cohort.

J Am Heart Assoc 2020 04 21;9(7):e013836. Epub 2020 Mar 21.

CarMeN Laboratory Centre de Recherche en Nutrition Humaine Rhône-Alpes Univ-Lyon Université Claude Bernard Lyon1 Hospices Civils de Lyon F-CRIN/FORCE Network Pierre Bénite, Lyon France.

Background The diet impact on cardiovascular diseases has been investigated widely, but the association between dietary patterns (DPs) and subclinical cardiovascular damage remains unclear. More informative DPs could be provided by considering metabolic syndrome components as intermediate markers. This study aimed to identify DPs according to generation and sex using reduced-rank regression (RRR) with metabolic syndrome components as intermediate markers and assess their associations with intima-media thickness, left ventricular mass, and carotid-femoral pulse-wave velocity in an initially healthy population-based family study. Methods and Results This study included 1527 participants from the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) cohort fourth examination. DPs were derived using reduced-rank regression according to generation (G1: age ≥50 years; G2: age <50 years) and sex. Associations between DPs and cardiovascular damage were analyzed using multivariable linear regression models. Although identified DPs were correlated between generations and sex, qualitative differences were observed: whereas only unhealthy DPs were found for both men generations, healthy DPs were identified in G2 ("fruity desserts") and G1 ("fiber and w3 oil") women. The "alcohol," "fast food and alcohol," "fried, processed, and dairy products," and "meat, starch, sodas, and fat" DPs in G1 and G2 men and in G1 and G2 women, respectively, were associated with high left ventricular mass (β [95% CI], 0.23 [0.10-0.36], 0.76 [0.00-1.52], 1.71 [0.16-3.26], and 1.80 [0.45-3.14]). The "alcohol" DP in G1 men was positively associated with carotid-femoral pulse-wave velocity (0.22 [0.09-0.34]). Conclusions The DPs that explain the maximum variation in metabolic syndrome components had different associations with subclinical cardiovascular damage across generation and sex. Our results indicate that dietary recommendations should be tailored according to age and sex. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01391442.
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http://dx.doi.org/10.1161/JAHA.119.013836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428593PMC
April 2020

Docosahexaenoic Acid (DHA) Bioavailability in Humans after Oral Intake of DHA-Containing Triacylglycerol or the Structured Phospholipid AceDoPC.

Nutrients 2020 Jan 18;12(1). Epub 2020 Jan 18.

Univ-Lyon, CarMeN Laboratory, Inserm UMR 1060, Inra UMR 1397, IMBL, INSA-Lyon, 69100 Villeurbanne, France.

AceDoPC is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the position; preventing the migration of DHA from the to position. In this study we aimed to know the bioavailability of C-labeled DHA after oral intake of a single dose of C-AceDoPC, in comparison with C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the C enrichment of DHA-containing lipids. C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC compared with TAG-DHA, peaking after 24 h in both cases. In red cells, C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion.
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http://dx.doi.org/10.3390/nu12010251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020088PMC
January 2020

OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions.

Obes Facts 2020 16;13(1):1-28. Epub 2020 Jan 16.

FCRIN/FORCE Network, Centre de Recherche en Nutrition Humaine Rhône-Alpes, Université de Lyon, Hospices Civils de Lyon, Lyon, France,

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.
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http://dx.doi.org/10.1159/000505342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098277PMC
September 2020

Seven-day overfeeding enhances adipose tissue dietary fatty acid storage and decreases myocardial and skeletal muscle dietary fatty acid partitioning in healthy subjects.

Am J Physiol Endocrinol Metab 2020 02 31;318(2):E286-E296. Epub 2019 Dec 31.

Division of Endocrinology, Department of Medicine, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14()-[F]fluoro-6-thia-heptadecanoic acid and [C]acetate positron emission tomography methods at the end of both interventions. HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCAL led to increased subcutaneous abdominal (+4.2 ± 1.6%, < 0.04) and thigh (+2.4 ± 1.2%, < 0.08) adipose tissue storage and reduced cardiac (-0.31 ± 0.11 mean standard uptake value [(SUV), < 0.03] and skeletal muscle (-0.17 ± 0.08 SUV, < 0.05) DFA partitioning without change in LV function. We conclude that early increase in adipose tissue DFA storage protects the heart and skeletal muscles from potential deleterious effects of DFA.
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http://dx.doi.org/10.1152/ajpendo.00474.2019DOI Listing
February 2020

Energy Expenditure in Older People Hospitalized for an Acute Episode.

Nutrients 2019 Dec 4;11(12). Epub 2019 Dec 4.

CarMeN, U1060 INSERM, 69921 Oullins CEDEX, France.

Weight loss and worsening of nutritional state is a frequent downfall of acute hospitalization in older people. It is usually accepted that acute inflammation is responsible for hypercatabolism. However, several studies suggest, on the contrary, a reduction in resting energy expenditure (REE). This study aimed to obtain a reliable measure of REE and total energy expenditure (TEE) in older patients hospitalized for an acute episode in order to better assess patients' energy requirements and help understand the mechanisms of weight loss in this situation. Nineteen hospitalized older patients (mean age 83 years) with C-reactive protein (CRP) level >20mg/L were recruited. REE and TEE were measured using gold standard methods of indirect calorimetry and doubly labeled water (DLW), respectively. REE was then compared to data from a previous study on aged volunteers from nursing homes who were free of an acute stressor event. Energy requirements measured by DLW were confirmed at 1.3 × REE. Energy intake covered the needs but did not prevent weight loss in these patients. TEE was not increased in hospitalized patients and was not influenced by inflammation, while the relationship between REE and inflammation was uncertain. Our results suggest that lean mass remains the major determinant of REE in hospitalized older people and that weight loss may not be explained solely by a state of hypercatabolism.
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http://dx.doi.org/10.3390/nu11122946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949974PMC
December 2019

Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes.

Diabetes Care 2019 10 21;42(10):2008-2010. Epub 2019 Aug 21.

French Network of Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS) and FIRENDO Network, Paris and Lyon, France

Objective: Anti-programmed cell death-1 (anti-PD-1) antibodies have revolutionized advanced cancer therapy. Anti-PD-1 therapy is responsible for immune-related adverse events, with frequent endocrine manifestations, including acute-onset type 1 diabetes. Acquired generalized lipodystrophy (AGL) is a rare disease, believed to be immune mediated, characterized by loss of adipose tissue and insulin resistance-associated complications.

Research Design And Methods: We describe the first reported case of AGL induced by immune checkpoint therapy.

Results: A 62-year-old woman with metastatic melanoma treated with nivolumab was referred for major hyperglycemia, hypertriglyceridemia, and nonalcoholic steatohepatitis. She had presented with a rapidly progressive generalized loss of subcutaneous adipose tissue. Diabetes was associated with severe insulin resistance and undetectable plasma leptin. Subcutaneous biopsy revealed atrophic adipose tissue infiltrated with cytotoxic CD8 T lymphocytes and fibrosis.

Conclusions: AGL is an additional immune-related adverse event of anti-PD-1 therapy that leads to severe insulin resistance-associated complications.
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http://dx.doi.org/10.2337/dc18-2535DOI Listing
October 2019

Relationship between food behavior and taste and smell alterations in cancer patients undergoing chemotherapy: A structured review.

Semin Oncol 2019 04 4;46(2):160-172. Epub 2019 Jun 4.

CNRS, UMR5292, INSERM U1028, Lyon Neuroscience Research Center, University Lyon, France. Electronic address:

Introduction: Taste and smell alteration is a frequent side effect of chemotherapy. However, little is known about their influence on patients' food behavior and the mechanisms underpinning their occurrence. This lack of clarity is likely due to a series of factors among which heterogeneity in chemotherapy-induced taste and smell modifications may play a prominent role. The present review provides a critical overview of the evidence on the association between taste and smell alterations and food behavior modifications in cancer patients undergoing chemotherapy.

Design: The literature search was performed using PubMed and Google Scholar databases and restricted to literature for English-language articles published between 1990 and June 2018. Sensory-related terms were combined with food behavior-related terms to identify the studies that examined the association between these two terms. The retrieved studies were grouped based on the taste and smell assessment outcomes.

Results: Thirteen eligible articles were included in the review. The studies varied in design, length, methodology of assessment, and studied population. The categorization of studies depending on taste and smell assessment outcomes allowed the definition of three patient profiles: unaltered, hypo- and hyperchemosensation (taste and/or smell). Alterations were significantly correlated with patients' energy intake and macronutrient preferences suggesting that sensitivity of each patient to olfactory and gustatory stimuli is likely to play a role in food behavior modulation during cancer and chemotherapy.

Conclusion: The review summarizes and provides relevant associations between taste/smell alterations and food behavior while receiving chemotherapy considering existing individual variations. Given the sensory influence on food behavior modulation, a better characterization of smell and taste alterations before the launch of chemotherapy seems important for a better understanding and management of patients' food behavior trajectory over the treatment.
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http://dx.doi.org/10.1053/j.seminoncol.2019.05.002DOI Listing
April 2019

Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay.

Gut 2020 03 12;69(3):487-501. Epub 2019 Jun 12.

Univ Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Charles Mérieux Medical School, 69600, Oullins, France.

Objective: To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health.

Design: A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients.

Results: Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut.

Conclusion: The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota.

Trial Registration Number: NCT02099032 and NCT02146339; Results.
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http://dx.doi.org/10.1136/gutjnl-2018-318155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034342PMC
March 2020

Attentional bias and response inhibition in severe obesity with food disinhibition: a study of P300 and N200 event-related potential.

Int J Obes (Lond) 2020 01 9;44(1):204-212. Epub 2019 Apr 9.

Centre Intégré de l'Obésité Rhône-Alpes; Fédération Hospitalo-Universitaire DO-iT, Service Endocrinologie-Diabète-Nutrition, Université de Lyon, Groupement Hospitalier Sud, Hospices Civils de Lyon, Lyon, France.

Background/objective: In obesity there is growing evidence for common mechanism between food intake regulation and substance use disorders, especially more attentional bias and less cognitive control. In the present study we investigated whether severely obese subjects with or without disordered eating exhibit electroencephalographic (EEG) event-related potential (ERP) modifications as observed in substance abusers.

Subjects/methods: A total of 90 women were included; 30 in the normal-weight (NW) group (18.5 < BMI < 24.5 kg/m; no food disinhibition or restriction on the Three-Factor Eating Questionnaire) and 60 participants with BMI ≥ 35 kg/m were separated into two groups (n = 30): without food disinhibition (disinhibition score ≤8; ObFD- group) and with food disinhibition (score >8; ObFD+). Clinical and metabolic parameters as well as compartmental aspects (Eating Disorders Inventory-2, EDI-2) were assessed. Participants underwent an ERP recording with an auditory oddball paradigm.

Results: The mean ± SD P300 amplitudes in Pz were significantly (p < 0.05) lower in ObFD- (12.4 ± 4.6) and ObFD+ (12.5 ± 4.4) groups than in the NW group (15.8 ± 5.9). The mean ± SD N200 amplitude in Cz was significantly lower in the ObFD- group (-2.0 ± 5.4) than in the NW group (-5.2 ± 4.2 vs; p = 0.035). N200 Cz amplitude was correlated with EDI-2 Binge eating risk score (ρ = 0.331; p = 0.01), EDI-2 Body Dissatisfaction score (ρ = 0.351; p = 0.007), and Drive for Thinness score (ρ = 0.26; p = 0.05).

Conclusions: The present study provides evidence for reduction of P300 and N200 amplitude in obese women and that N200 amplitude may be related to more disordered eating and eating disorder risk. This leads to consider attentional bias and response inhibition as core mechanisms in obesity and as possible targets for new therapeutic strategy.
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http://dx.doi.org/10.1038/s41366-019-0360-xDOI Listing
January 2020

Omega-3 Polyunsaturated Fatty Acids Inhibit IL-17A Secretion through Decreased ICAM-1 Expression in T Cells Co-Cultured with Adipose-Derived Stem Cells Harvested from Adipose Tissues of Obese Subjects.

Mol Nutr Food Res 2019 06 20;63(11):e1801148. Epub 2019 Mar 20.

INSERM U 1060-CarMen, University Claude Bernard Lyon I, 165 Chemin du Grand Revoyet, 69310, Pierre Bénite, France.

Scope: Obese adipose tissue (AT) is infiltrated by inflammatory immune cells including IL-17A-producing-T (Th17) cells. It has been previously demonstrated that adipose-derived stem cells from obese (ob-ASCs), but not lean AT promote Th17 cells. Because n-3 PUFAs are known to inhibit obese AT inflammation, it is tested here whether they could inhibit ob-ASC-mediated IL-17A secretion.

Methods And Results: The n-3 PUFA precursor, alpha-linolenic acid (ALA), or its derivatives, eicosapentaenoic, or docosahexaenoic acid, is added to co-cultures of human ob-ASCs and mononuclear cells (MNCs). All three inhibited IL-17A, but not IL-1β, IL-6, nor TNFα  secretion. As a control, palmitic acid (PA), a saturated fatty acid, did not inhibit IL-17A secretion. ALA also inhibited IL-17A secretion mediated by adipocytes differentiated from ob-ASCs. Toll-like-receptor 4 is shown to be involved in ob-ASC-mediated-IL-17A secretion, and to be inhibited by ALA, together with Cyclo-Oxygenase-2 and Signal-Transducer-and-Activator-of-transcription-3. In addition, ALA down-regulated Intercellular-Adhesion-Molecule-1 (ICAM-1) expression in both monocytes and ASCs, which resulted in decreased interactions between ob-ASCs and MNCs, and inhibition of IL-17A secretion.

Conclusion: It is demonstrated herein that ALA inhibits Th17 cell promotion, through decreased ICAM-1expression in both ob-ASCs and monocytes. This novel mechanism may contribute to explain the beneficial effects of n-3 PUFA in IL-17A-related inflammatory pathologies.
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http://dx.doi.org/10.1002/mnfr.201801148DOI Listing
June 2019

3D Chemical Shift-Encoded MRI for Volume and Composition Quantification of Abdominal Adipose Tissue During an Overfeeding Protocol in Healthy Volunteers.

J Magn Reson Imaging 2019 06 16;49(6):1587-1599. Epub 2018 Oct 16.

Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, F69621, Lyon, France.

Background: Overweight and obesity are major worldwide health concerns characterized by an abnormal accumulation of fat in adipose tissue (AT) and liver.

Purpose: To evaluate the volume and the fatty acid (FA) composition of the subcutaneous adipose tissue (SAT) and the visceral adipose tissue (VAT) and the fat content in the liver from 3D chemical-shift-encoded (CSE)-MRI acquisition, before and after a 31-day overfeeding protocol.

Study Type: Prospective and longitudinal study.

Subjects: Twenty-one nonobese healthy male volunteers.

Field Strength/sequence: A 3D spoiled-gradient multiple echo sequence and STEAM sequence were performed at 3T.

Assessment: AT volume was automatically segmented on CSE-MRI between L2 to L4 lumbar vertebrae and compared to the dual-energy X-ray absorptiometry (DEXA) measurement. CSE-MRI and MR spectroscopy (MRS) data were analyzed to assess the proton density fat fraction (PDFF) in the liver and the FA composition in SAT and VAT. Gas chromatography-mass spectrometry (GC-MS) analyses were performed on 13 SAT samples as a FA composition countermeasure.

Statistical Tests: Paired t-test, Pearson's correlation coefficient, and Bland-Altman plots were used to compare measurements.

Results: SAT and VAT volumes significantly increased (P < 0.001). CSE-MRI and DEXA measurements were strongly correlated (r = 0.98, P < 0.001). PDFF significantly increased in the liver (+1.35, P = 0.002 for CSE-MRI, + 1.74, P = 0.002 for MRS). FA composition of SAT and VAT appeared to be consistent between localized-MRS and CSE-MRI (on whole segmented volume) measurements. A significant difference between SAT and VAT FA composition was found (P < 0.001 for CSE-MRI, P = 0.001 for MRS). MRS and CSE-MRI measurements of the FA composition were correlated with the GC-MS results (for ndb: r  = 0.83 P < 0.001, r  = 0.84, P = 0.001; for nmidb: r  = 0.74, P = 0.006, r  = 0.66, P = 0.020) DATA CONCLUSION: The follow-up of liver PDFF, volume, and FA composition of AT during an overfeeding diet was demonstrated through different methods. The CSE-MRI sequence associated with a dedicated postprocessing was found reliable for such quantification.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1587-1599.
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http://dx.doi.org/10.1002/jmri.26532DOI Listing
June 2019

Adipose Tissue Expansion by Overfeeding Healthy Men Alters Iron Gene Expression.

J Clin Endocrinol Metab 2019 03;104(3):688-696

Univ-Lyon, CarMeN Laboratory, and Centre de Recherche en Nutrition Humaine Rhône-Alpes, Université Claude Bernard Lyon1, Pierre Benite, France.

Context: Iron overload has been associated with greater adipose tissue (AT) depots. We retrospectively studied the potential interactions between iron and AT during an experimental overfeeding in participants without obesity.

Methods: Twenty-six participants (mean body mass index ± SD, 24.7 ± 3.1 kg/m2) underwent a 56-day overfeeding (+760 kcal/d). Serum iron biomarkers (ELISA), subcutaneous AT (SAT) gene expression, and abdominal AT distribution assessed by MRI were analyzed at the beginning and the end of the intervention.

Results: Before intervention: SAT mRNA expression of the iron transporter transferrin (Tf) was positively correlated with the expression of genes related to lipogenesis (lipin 1, ACSL1) and lipid storage (SCD). SAT expression of the ferritin light chain (FTL) gene, encoding ferritin (FT), an intracellular iron storage protein, was negatively correlated to SREBF1, a gene related to lipogenesis. Serum FT (mean, 92 ± 57 ng/mL) was negatively correlated with the expression of SAT genes linked to lipid storage (SCD, DGAT2) and to lipogenesis (SREBF1, ACSL1). After intervention: Overfeeding led to a 2.3 ± 1.3-kg weight gain. In parallel to increased expression of lipid storage-related genes (mitoNEET, SCD, DGAT2, SREBF1), SAT Tf, SLC40A1 (encoding ferroportin 1, a membrane iron export channel) and hephaestin mRNA levels increased, whereas SAT FTL mRNA decreased, suggesting increased AT iron requirement. Serum FT decreased to 67 ± 43 ng/mL. However, no significant associations between serum iron biomarkers and AT distribution or expansion were observed.

Conclusion: In healthy men, iron metabolism gene expression in SAT is associated with lipid storage and lipogenesis genes expression and is modulated during a 56-day overfeeding diet.
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http://dx.doi.org/10.1210/jc.2018-01169DOI Listing
March 2019

MFN2-associated lipomatosis: Clinical spectrum and impact on adipose tissue.

J Clin Lipidol 2018 Nov - Dec;12(6):1420-1435. Epub 2018 Jul 25.

Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-métabolisme et Nutrition (ICAN), Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, Paris, France.

Background: Multiple symmetric lipomatosis (MSL) is characterized by upper-body lipomatous masses frequently associated with metabolic and neurological signs. MFN2 pathogenic variants were recently implicated in a very rare autosomal recessive form of MSL. MFN2 encodes mitofusin-2, a mitochondrial fusion protein previously involved in Charcot-Marie-Tooth neuropathy.

Objective: To investigate the clinical, metabolic, tissular, and molecular characteristics of MFN2-associated MSL.

Methods: We sequenced MFN2 in 66 patients referred for altered fat distribution with one or several lipomas or lipoma-like regions and performed clinical and metabolic investigations in patients with positive genetic testing. Lipomatous tissues were studied in 3 patients.

Results: Six patients from 5 families carried a homozygous p.Arg707Trp pathogenic variant, representing the largest reported series of MFN2-associated MSL. Patients presented both lipomatous masses and a lipodystrophic syndrome (lipoatrophy, low leptinemia and adiponectinemia, hypertriglyceridemia, insulin resistance and/or diabetes). Charcot-Marie-Tooth neuropathy was of highly variable clinical severity. Lipomatous tissue mainly contained hyperplastic unilocular adipocytes, with few multilocular cells. It displayed numerous mitochondrial alterations (increased number and size, structural defects). As compared to control subcutaneous fat, mRNA and protein expression of leptin and adiponectin was strikingly decreased, whereas the CITED1 and fibroblast growth factor 21 (FGF21) thermogenic markers were strongly overexpressed. Consistently, serum FGF21 was markedly increased, and F-FDG-PET-scan revealed increased fat metabolic activity.

Conclusion: MFN2-related MSL is a novel mitochondrial lipodystrophic syndrome involving both lipomatous masses and lipoatrophy. Its complex neurological and metabolic phenotype justifies careful clinical evaluation and multidisciplinary care. Low leptinemia and adiponectinemia, high serum FGF21, and increased F-FDG body fat uptake may be disease markers.
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http://dx.doi.org/10.1016/j.jacl.2018.07.009DOI Listing
October 2019

Comparison of MRI-derived vs. traditional estimations of fatty acid composition from MR spectroscopy signals.

NMR Biomed 2018 09 24;31(9):e3991. Epub 2018 Jul 24.

Université Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France.

Introduction: The composition of fatty acids in the body is gaining increasing interest, and can be followed up noninvasively by quantitative magnetic resonance spectroscopy (MRS). However, current MRS quantification methods have been shown to provide different quantitative results in terms of lipid signals, with possible varying outcomes for a given biological examination. Quantitative magnetic resonance imaging using multigradient echo sequence (MGE-MRI) has recently been added to MRS approaches. In contrast, these methods fit the undersampled magnetic resonance temporal signal with a simplified model function (expressing the triglyceride [TG] spectrum with only three TG parameters), specific implementations and prior knowledge. In this study, an adaptation of an MGE-MRI method to MRS lipid quantification is proposed.

Methods: Several versions of the method - with time data fully or undersampled, including or excluding the spectral peak T knowledge in the fitting - were compared theoretically and on Monte Carlo studies with a time-domain, peak-fitting approach. Robustness, repeatability and accuracy were also inspected on in vitro oil acquisitions and test-retest in vivo subcutaneous adipose tissue acquisitions, adding results from the reference LCModel method.

Results: On simulations, the proposed method provided TG parameter estimates with the smallest variability, but with a possible bias, which was mitigated by fitting on undersampled data and considering peak T values. For in vitro measurements, estimates for all approaches were correlated with theoretical values and the best concordance was found for the usual MRS method (LCModel and peak fitting). Limited in vivo test-retest variability was found (4.1% for PUFAindx, 0.6% for MUFAindx and 3.6% for SFAindx), as for LCModel (7.6% for PUFAindx, 7.8% for MUFAindx and 3.0% for SFAindx).

Conclusion: This study shows that fitting the three TG parameters directly on MRS data is one valuable solution to circumvent the poor conditioning of the MRS quantification problem.
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http://dx.doi.org/10.1002/nbm.3991DOI Listing
September 2018

Physical activity, energy expenditure and sedentary parameters in overfeeding studies - a systematic review.

BMC Public Health 2018 07 21;18(1):903. Epub 2018 Jul 21.

École de kinésiologie et des sciences de l'activité physique, Université de Montréal, P.O. Box 6128, Downtown Station, Montreal, Quebec, H3C 3J7, Canada.

Background: It has been proposed that compensations in physical activity, energy expenditure and sedentary parameters can occur as a result of overfeeding studies in order to maintain body weight; however, the evidence has not yet been systematically reviewed.

Methods: The current study systematically reviewed the literature on this subject to determine the common tools used in overfeeding studies and to explore whether overfeeding produces changes in physical activity, energy expenditure and sedentary parameters. Eight electronic databases were searched to identify experimental studies using keywords pertaining to overfeeding, exercise, physical activity and sedentariness. Articles included healthy adults (aged 18-64 years) participating in an overfeeding study that examined at least one parameter of sedentary, energy expenditure or physical activity. Of 123 full-text articles reviewed, 15 met the inclusion criteria.

Results: The common tools used in overfeeding studies were doubly labeled water (n = 6), room calorimeter (n = 4), accelerometer (n = 7), pedometer (n = 3), radar sensor (n = 4) and survey (n = 1). Parameters partaining to energy expenditure increased between 7 to 50% with different overfeeding duration. Physical activity parameters, such as number of steps and spontaneous activity, increased or decreased significantly in three studies, while five studies showed no significant change. Sedentary parameters were examined by only one study and its results were not significant after 3 days of overfeeding. Methodological issues existed concerning the small number of studies, disparities in sedentary and physical activity parameters and various definitions of free-living experimental conditions and physical activity limits.

Conclusions: There is actually a use of many tools and a large variation of parameters for physical activity in overfeeding studies. Contradictory findings showed changes in physical activity parameters following overfeeding and limited findings support the absence of changes in sedentariness. While energy expenditure parameters are more numerous and all show an increase after an overfeeding period, further studies are required to confirm changes in physical activity and sedentary parameters.
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http://dx.doi.org/10.1186/s12889-018-5801-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054727PMC
July 2018