Publications by authors named "André Marette"

195 Publications

Purple grumixama anthocyanins (Eugenia brasiliensis Lam.) attenuate obesity and insulin resistance in high-fat diet mice.

Food Funct 2021 Apr 1;12(8):3680-3691. Epub 2021 Apr 1.

Food Research Center-(FoRC-CEPID) and Department of Food Science and Experimental Nutrition, School of Pharmaceutical Science, University of São Paulo, São Paulo, SP, Brazil.

Some polyphenols have been reported to modulate the expression of several genes related to lipid metabolism and insulin signaling, ameliorating metabolic disorders. We investigated the potential for the polyphenols of two varieties of grumixama, the purple fruit rich in anthocyanins and the yellow fruit, both also rich in ellagitannins, to attenuate obesity-associated metabolic disorders. Mice were fed a high fat and high sucrose diet, supplemented daily with yellow and purple extracts (200 mg per kg of body weight) for eight weeks. Purple grumixama supplementation was found to decrease body weight gain, improve insulin sensitivity and glucose-induced hyperinsulinemia, and reduce hepatic triglyceride accumulation. A decrease in intrahepatic lipids in mice treated with the purple grumixama extract was associated with lipid metabolism modulation by the PPAR signaling pathway. LPL, ApoE, and LDLr were found to be down-regulated, while Acox1 and ApoB were found to be upregulated. Some of these genes were also modulated by the yellow extract. In addition, both extracts decreased oGTT and plasma LPS. The results were associated with the presence of phenolic acids and urolithins. In conclusion, most likely the anthocyanins from the purple grumixama phenolic extract is responsible for reducing obesity and insulin resistance.
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http://dx.doi.org/10.1039/d0fo03245jDOI Listing
April 2021

Reply to: "Dietary sucrose induces atherosclerotic diseases more than dietary fat in LDLrApoB mice: Is it independent of differences in plasma cholesterol levels?"

Atherosclerosis 2021 Apr 5. Epub 2021 Apr 5.

Quebec Heart and Lung Institute, Department of Medicine, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada; Institute of Nutraceuticals and Functional Foods, Laval University, Quebec City, Quebec, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.038DOI Listing
April 2021

Dietary fat and low fiber in purified diets differently impact the gut-liver axis to promote obesity-linked metabolic impairments.

Am J Physiol Gastrointest Liver Physiol 2021 Apr 21. Epub 2021 Apr 21.

Université Laval.

Purified high-fat diets are commonly used to promote obesity and metabolic disturbances in animal models. However, most studies also use unpurified chow (low in fat, high in fiber content) as a "healthy" diet which can impact gut health. Here, we investigated the impact of feeding chow or purified diets varying in fat content on metabolic and intestinal functions in relation with temporal changes in gut microbiota composition. C57BL/6J male mice were fed either chow or purified low-fat (LF) or high-fat (HF) diet for 12 weeks. LF-fed mice displayed similar glucose and insulin homeostasis and bile acid profile than chow-fed mice but did exhibit higher fasting insulinemia and impaired insulin clearance, which was associated with increased weight gain and fat mass. Compared with chow, feeding LF or HF diets increased hepatic steatosis and inflammation, and impaired intestinal integrity. Changes in gut microbiota preceded these effects, with both purified diets inducing rapid and dramatic decrease of bacterial diversity and short chain fatty acid (SCFA) production. Importantly, branched SCFA levels increased only in HF-fed mice suggesting that this response is driven by excessive dietary fat rather than lack of fiber content. LF-fed mucus-associated microbial composition was also closer to that of chow-fed mice than that of HF-fed mice, suggesting the impact of fat content on this specific microbial community. We have identified distinct and overlapping gut microbiome and metabolic impairments caused by low fiber or high-fat contents in HF-fed animals, revealing their selective mechanisms underpinning the gastrointestinal and metabolic impacts in obesity.
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http://dx.doi.org/10.1152/ajpgi.00028.2021DOI Listing
April 2021

Cholecalciferol Supplementation Does Not Prevent the Development of Metabolic Syndrome or Enhance the Beneficial Effects of Omega-3 Fatty Acids in Obese Mice.

J Nutr 2021 Apr 13. Epub 2021 Apr 13.

Québec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Québec City, QC, Canada.

Background: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood.

Objectives: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice.

Methods: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA.

Results: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa.

Conclusions: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.
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http://dx.doi.org/10.1093/jn/nxab002DOI Listing
April 2021

Fish oil replacement prevents, while docosahexaenoic acid-derived protectin DX mitigates end-stage-renal-disease in atherosclerotic diabetic mice.

FASEB J 2021 May;35(5):e21559

Quebec Heart and Lung Institute, Laval University, Quebec, QC, Canada.

Diabetic nephropathy (DN) remains the major cause of end-stage renal disease (ESRD). We used high-fat/high-sucrose (HFHS)-fed LDLr /ApoB mice with transgenic overexpression of IGFII in pancreatic β-cells (LRKOB100/IGFII) as a model of ESRD to test whether dietary long chain omega-3 polyunsaturated fatty acids LCω3FA-rich fish oil (FO) could prevent ESRD development. We further evaluated the potential of docosahexaenoic acid (DHA)-derived pro-resolving lipid mediators, 17-hydroxy-DHA (17-HDHA) and Protectin DX (PDX), to reverse established ESRD damage. HFHS-fed vehicle-treated LRKOB100/IGFII mice developed severe kidney dysfunction leading to ESRD, as revealed by advanced glomerular fibrosis and mesangial expansion along with reduced percent survival. The kidney failure outcome was associated with cardiac dysfunction, revealed by reduced heart rate and prolonged diastolic and systolic time. Dietary FO prevented kidney damage, lean mass loss, cardiac dysfunction, and death. 17-HDHA reduced podocyte foot process effacement while PDX treatment alleviated kidney fibrosis and mesangial expansion as compared to vehicle treatment. Only PDX therapy was effective at preserving the heart function and survival rate. These results show that dietary LCω3FA intake can prevent ESRD and cardiac dysfunction in LRKOB100/IGFII diabetic mice. Our data further reveals that PDX can protect against renal failure and cardiac dysfunction, offering a potential new therapeutic strategy against ESRD.
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http://dx.doi.org/10.1096/fj.202100073RDOI Listing
May 2021

Perspective: Nutritional Strategies Targeting the Gut Microbiome to Mitigate COVID-19 Outcomes.

Adv Nutr 2021 Mar 30. Epub 2021 Mar 30.

Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada.

More than a year has passed since the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection in the city of Wuhan in China's Hubei Province. Until now, few antiviral medications (e.g., remdesivir) or drugs that target inflammatory complications associated with SARS-CoV2 infection have been considered safe by public health authorities. By the end of November 2020, this crisis had led to >1 million deaths and revealed the high susceptibility of people with pre-existing comorbidities (e.g., obesity, diabetes, coronary heart disease, hypertension) to suffer from a severe form of the disease. Elderly people have also been found to be highly susceptible to SARS-CoV2 infection and morbidity. Gastrointestinal manifestations and gut microbial alterations observed in SARS-CoV2-infected hospitalized patients have raised awareness of the potential role of intestinal mechanisms in increasing the severity of the disease. It is therefore critically important to find alternative or complementary approaches, not only to prevent or treat the disease, but also to reduce its growing societal and economic burden. In this review, we explore potential nutritional strategies that implicate the use of polyphenols, probiotics, vitamin D, and ω-3 fatty acids with a focus on the gut microbiome, and that could lead to concrete recommendations that are easily applicable to both vulnerable people with pre-existing metabolic comorbidities and the elderly, but also to the general population.
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http://dx.doi.org/10.1093/advances/nmab031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083677PMC
March 2021

High-Fat Diet Modulates Hepatic Amyloid β and Cerebrosterol Metabolism in the Triple Transgenic Mouse Model of Alzheimer's Disease.

Hepatol Commun 2021 Mar 18;5(3):446-460. Epub 2020 Dec 18.

Axe Neurosciences Centre De Recherche du CHU de Québec-Université Laval Québec Canada.

Obesity and diabetes are strongly associated not only with fatty liver but also cognitive dysfunction. Moreover, their presence, particularly in midlife, is recognized as a risk factor for Alzheimer's disease (AD). AD, the most common cause of dementia, is increasingly considered as a metabolic disease, although underlying pathogenic mechanisms remain unclear. The liver plays a major role in maintaining glucose and lipid homeostasis, as well as in clearing the AD neuropathogenic factor amyloid-β (Aβ) and in metabolizing cerebrosterol, a cerebral-derived oxysterol proposed as an AD biomarker. We hypothesized that liver impairment induced by obesity contributes to AD pathogenesis. We show that the AD triple transgenic mouse model (3xTg-AD) fed a chow diet presents a hepatic phenotype similar to nontransgenic controls (NTg) at 15 months of age. A high-fat diet (HFD), started at the age of 6 months and continued for 9 months, until sacrifice, induced hepatic steatosis in NTg, but not in 3xTg-AD mice, whereas HFD did not induce changes in hepatic fatty acid oxidation, lipogenesis, and gluconeogenesis. HFD-induced obesity was associated with a reduction of insulin-degrading enzyme, one of the main hepatic enzymes responsible for Aβ clearance. The hepatic rate of cerebrosterol glucuronidation was lower in obese 3xTg-AD than in nonobese controls ( < 0.05) and higher compared with obese NTg ( < 0.05), although circulating levels remained unchanged. Modulation of hepatic lipids, Aβ, and cerebrosterol metabolism in obese 3xTg-AD mice differs from control mice. This study sheds light on the liver-brain axis, showing that the chronic presence of NAFLD and changes in liver function affect peripheral AD features and should be considered during development of biomarkers or AD therapeutic targets.
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http://dx.doi.org/10.1002/hep4.1609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917280PMC
March 2021

Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3RORγtIL-17 Tregs and improve metabolism.

Nat Commun 2021 02 17;12(1):1093. Epub 2021 Feb 17.

Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Oslo, Norway.

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3RORγtIL-17) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.
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http://dx.doi.org/10.1038/s41467-021-21408-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889900PMC
February 2021

Deletion of intestinal epithelial AMP-activated protein kinase alters distal colon permeability but not glucose homeostasis.

Mol Metab 2021 May 4;47:101183. Epub 2021 Feb 4.

Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France. Electronic address:

Objective: The intestinal epithelial barrier (IEB) restricts the passage of microbes and potentially harmful substances from the lumen through the paracellular space, and rupture of its integrity is associated with a variety of gastrointestinal disorders and extra-digestive diseases. Increased IEB permeability has been linked to disruption of metabolic homeostasis leading to obesity and type 2 diabetes. Interestingly, recent studies have uncovered compelling evidence that the AMP-activated protein kinase (AMPK) signaling pathway plays an important role in maintaining epithelial cell barrier function. However, our understanding of the function of intestinal AMPK in regulating IEB and glucose homeostasis remains sparse.

Methods: We generated mice lacking the two α1 and α2 AMPK catalytic subunits specifically in intestinal epithelial cells (IEC AMPK KO) and determined the physiological consequences of intestinal-specific deletion of AMPK in response to high-fat diet (HFD)-induced obesity. We combined histological, functional, and integrative analyses to ascertain the effects of gut AMPK loss on intestinal permeability in vivo and ex vivo and on the development of obesity and metabolic dysfunction. We also determined the impact of intestinal AMPK deletion in an inducible mouse model (i-IEC AMPK KO) by measuring IEB function, glucose homeostasis, and the composition of gut microbiota via fecal 16S rRNA sequencing.

Results: While there were no differences in in vivo intestinal permeability in WT and IEC AMPK KO mice, ex vivo transcellular and paracellular permeability measured in Ussing chambers was significantly increased in the distal colon of IEC AMPK KO mice. This was associated with a reduction in pSer425 GIV phosphorylation, a marker of leaky gut barrier. However, the expression of tight junction proteins in intestinal epithelial cells and pro-inflammatory cytokines in the lamina propria were not different between genotypes. Although the HFD-fed AMPK KO mice displayed suppression of the stress polarity signaling pathway and a concomitant increase in colon permeability, loss of intestinal AMPK did not exacerbate body weight gain or adiposity. Deletion of AMPK was also not sufficient to alter glucose homeostasis or the acute glucose-lowering action of metformin in control diet (CD)- or HFD-fed mice. CD-fed i-IEC AMPK KO mice also presented higher permeability in the distal colon under homeostatic conditions but, surprisingly, this was not detected upon HFD feeding. Alteration in epithelial barrier function in the i-IEC AMPK KO mice was associated with a shift in the gut microbiota composition with higher levels of Clostridiales and Desulfovibrionales.

Conclusions: Altogether, our results revealed a significant role of intestinal AMPK in maintaining IEB integrity in the distal colon but not in regulating glucose homeostasis. Our data also highlight the complex interaction between gut microbiota and host AMPK.
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http://dx.doi.org/10.1016/j.molmet.2021.101183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921883PMC
May 2021

Nucleation Points: The Forgotten Parameter in the Synthesis of Hydrogel-Coated Gold Nanoparticles.

Polymers (Basel) 2021 Jan 26;13(3). Epub 2021 Jan 26.

Centre D'optique, Photonique et Laser (COPL), Université Laval, Québec, QC G1V 0A6, Canada.

The implementation of gold-hydrogel core-shell nanomaterials in novel light-driven technologies requires the development of well-controlled and scalable synthesis protocols with precisely tunable properties. Herein, new insights are presented concerning the importance of using the concentration of gold cores as a control parameter in the seeded precipitation polymerization process to modulate-regardless of core size-relevant fabrication parameters such as encapsulation yield, particle size and shrinkage capacity. Controlling the number of nucleation points results in the facile tuning of the encapsulation process, with yields reaching 99% of gold cores even when using different core sizes at a given particle concentration. This demonstration is extended to the encapsulation of bimodal gold core mixtures with equally precise control on the encapsulation yield, suggesting that this principle could be extended to encapsulating cores composed of other materials. These findings could have a significant impact on the development of stimuli-responsive smart materials.
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http://dx.doi.org/10.3390/polym13030373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865208PMC
January 2021

Effects of Daily Raspberry Consumption on Immune-Metabolic Health in Subjects at Risk of Metabolic Syndrome: A Randomized Controlled Trial.

Nutrients 2020 Dec 17;12(12). Epub 2020 Dec 17.

Centre Nutrition, Santé et Société (NUTRISS) and Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC G1V 0A6, Canada.

Consumption of red raspberries has been reported to exert acute beneficial effects on postprandial glycemia, insulinemia, triglyceridemia, and cytokine levels in metabolically disturbed subjects. In a two-arm parallel-group, randomized, controlled trial, 59 subjects with overweight or abdominal obesity and with slight hyperinsulinemia or hypertriglyceridemia were randomized to consume 280 g/day of frozen raspberries or to maintain their usual diet for 8 weeks. Primary analyses measured metabolic differences between the groups. Secondary analyses performed with omics tools in the intervention group assessed blood gene expression and plasma metabolomic changes following the raspberry supplementation. The intervention did not significantly affect plasma insulin, glucose, inflammatory marker concentrations, nor blood pressure. Following the supplementation, 43 genes were differentially expressed, and several functional pathways were enriched, a major portion of which were involved in the regulation of cytotoxicity, immune cell trafficking, protein signal transduction, and interleukin production. In addition, 10 serum metabolites were found significantly altered, among which β-alanine, trimethylamine N-oxide, and bioactive lipids. Although the supplementation had no meaningful metabolic effects, these results highlight the impact of a diet rich in raspberry on the immune function and phospholipid metabolism, thus providing novel insights into potential immune-metabolic pathways influenced by regular raspberry consumption.
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http://dx.doi.org/10.3390/nu12123858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767072PMC
December 2020

Metabolic responses to intermittent hypoxia are regulated by sex and estradiol in mice.

Am J Physiol Endocrinol Metab 2021 02 7;320(2):E316-E325. Epub 2020 Dec 7.

Faculté de Médecine, Département de Pédiatrie, Axe Pneumologie, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec, Canada.

The roles of sex and sex-hormones on the metabolic consequences of intermittent hypoxia (IH, a reliable model of sleep apnea) are unknown. We used intact male or female mice and ovariectomized (OVX) females treated with vehicle (Veh) or estradiol (E) and exposed to normoxia (Nx) or IH (6% O, 10 cycles/h, 12 h/day, 2 wk). Mice were then fasted for 6 h, and we measured fasting glucose and insulin levels and performed insulin or glucose tolerance tests (ITT or GTT). We also assessed liver concentrations of glycogen, triglycerides (TGs), and expression levels of genes involved in aerobic or anaerobic metabolism. In males, IH lowered fasting levels of glucose and insulin, slightly improved glucose tolerance, but altered glucose tolerance in females. In OVX-Veh females, IH reduced fasting glucose and insulin levels and strongly impaired glucose tolerance. E supplementation reversed these effects and improved homeostasis model assessment of β-cell function (HOMA-β), a marker of pancreatic glucose-induced insulin released. IH decreased liver TG concentration in males and slightly increased glycogen in OVX-Veh females. Liver expression of glycolytic () and mitochondrial (citrate synthase, ) genes was reduced by IH in males and in OVX-Veh females, but not in intact or OVX-E females. We conclude that ) IH reduced fasting levels of glycemia in males and in ovariectomized females. ) IH improves glucose tolerance only in males. ) In females IH decreased glucose tolerance, this effect was amplified by ovariectomy, and reversed by E supplementation. ) During IH exposures, E supplementation appears to improve pancreatic β cells functions. We assessed fasting glycemic control, and tolerance to insulin and glucose in male and female mice exposed to intermittent hypoxia. IH improves glucose tolerance in males but had opposite effects in females. This response was amplified following ovariectomy in females and prevented by estradiol supplementation. Metabolic consequences of IH differ between males and females and are regulated by estradiol in female mice.
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http://dx.doi.org/10.1152/ajpendo.00272.2020DOI Listing
February 2021

Omega-3 Eicosapentaenoic Acid Reduces Prostate Tumor Vascularity.

Mol Cancer Res 2021 03 1;19(3):516-527. Epub 2020 Dec 1.

Laboratoire d'Uro-Oncologie Expérimentale, Oncology Axis, Centre de recherche du CHU de Québec-Université Laval, Québec, Québec, Canada.

The impact of omega (ω)-3 fatty acids on prostate cancer is controversial in epidemiological studies but experimental studies suggest a protective effect. However, little is known about the mechanism of action. Here, we studied the effects of purified fatty acid molecules on prostate tumor progression using the TRAMP-C2 syngeneic immunocompetent mouse model. Compared with ω-6 or ω-9-supplemented animals, we observed that late-stage prostate tumor growth was reduced with a monoacylglyceride (MAG)-conjugated form of eicosapentaenoic acid (EPA) supplementation, whereas docosahexanenoic acid (DHA) caused an early reduction. MAG-EPA significantly decreased tumor blood vessel diameter ( < 0.001). RNA sequencing analysis revealed that MAG-EPA downregulated angiogenesis- and vascular-related pathways in tumors. We also observed this tissue vascular phenotype in a clinical trial testing MAG-EPA versus a high oleic sunflower oil placebo. Using anti-CD31 IHC, we observed that MAG-EPA reduced blood vessel diameter in prostate tumor tissue ( = 0.03) but not in normal adjacent tissue. Finally, testing autocrine and paracrine effects in an avascular tumor spheroid growth assay, both exogenous MAG-EPA and endogenous ω3 reduced VEGF secretion and endothelial cell tube formation and blocked tumor spheroid growth, suggesting that ω3 molecules can directly hinder prostate cancer cell growth. Altogether, our results suggest that fatty acids regulate prostate cancer growth and that a tumor-specific microenvironment is required for the anti-vascular effect of MAG-EPA in patients with prostate cancer. IMPLICATIONS: Increasing the amount of ingested EPA omega-3 subtype for patients with prostate cancer might help to reduce prostate tumor progression by reducing tumor vascularization.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0316DOI Listing
March 2021

A polyphenol-rich cranberry extract protects against endogenous exposure to persistent organic pollutants during weight loss in mice.

Food Chem Toxicol 2020 Dec 28;146:111832. Epub 2020 Oct 28.

Quebec Heart & Lung Institute, Université Laval, 2725 Ch Ste-Foy, Québec, QC, G1V 4G5, Canada; Institute of Nutrition and Functional Foods, Université Laval, 2440 Boulevard Hochelaga Suite 1710, Québec, QC, G1V 0A6, Canada; Department of Medicine, Faculty of Medicine, Université Laval, 1050 Avenue de la Médecine, Québec, QC, G1V 0A6, Canada. Electronic address:

The dramatic rise in the global occurrence of obesity and associated diseases calls for new strategies to promote weight loss. However, while the beneficial effects of weight loss are well known, rapid loss of fat mass can also lead to the endogenous release of liposoluble molecules with potential harmful effects, such as persistent organic pollutants (POP). The aim of this study was to evaluate the impact of a polyphenol-rich cranberry extract (CE) on POP release and their potential deleterious effects during weight loss of obese mice. C57BL/6 J mice were fed an obesogenic diet with or without a mixture of POP for 12 weeks and then changed to a low-fat diet to induce weight loss and endogenous POP release. The POP-exposed mice were then separated in two groups during weight loss, receiving either CE or the vehicle. Unexpectedly, despite the higher fat loss in the CE-treated group, the circulating levels of POP were not enhanced in these mice. Moreover, glucose homeostasis was further improved during CE-induced weight loss, as revealed by lower fasting glycemia and improved glucose tolerance as compared to vehicle-treated mice. Interestingly, the CE extract also induced changes in the gut microbiota after weight loss in POP-exposed mice, including blooming of Parvibacter, a member of the Coriobacteriaceae family which has been predicted to play a role in xenobiotic metabolism. Our data thus suggests that the gut microbiota can be targeted by polyphenol-rich extracts to protect from increased POP exposure and their detrimental metabolic effects during rapid weight loss.
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http://dx.doi.org/10.1016/j.fct.2020.111832DOI Listing
December 2020

Characterization of a Coproduct from the Sea Cucumber and Its Effects on Visceral Adipocyte Size in Male Wistar Rats.

Mar Drugs 2020 Oct 26;18(11). Epub 2020 Oct 26.

School of Nutrition, Faculty of Agricultural and Food Sciences, Université Laval, Laval, QC G1V 0A6, Canada.

Sea cucumbers have been shown to have potential health benefits and are a rich source of several bioactive compounds, particularly triterpenoid saponins. However, most studies concentrate on the body wall, and little is known about the health effects of the coproducts. The objectives of this study were to determine the nutritional composition of a coproduct from the sea cucumber and the effects of the dietary consumption of this coproduct on cardiometabolic health in rats. Chemical, biochemical, and nutritional analyses were performed to characterize this coproduct. Forty (40) male Wistar rats were then equally divided into four groups and fed a purified control diet or a diet enriched with 0.5%, 1.5%, or 2.5% (by protein) of coproduct. After 28 days of feeding, the rats were sacrificed. Body and tissue weight, body composition, epididymal adipocyte diameter, plasma and hepatic lipids, glycemia, and insulinemia were measured at the end of the 28-day experiment. Analysis of the coproduct revealed high levels of protein, omega-3 fatty acids, minerals, and saponins. The 1.5% group had significantly smaller epididymal adipocytes vs. the control. We conclude that dietary administration of this sea cucumber coproduct at 1.5% doses decreases visceral adiposity, potentially decreasing the risk of cardiometabolic dysfunction. The coproduct's saponin content may contribute to the observed effects, but the impact of other components cannot be ruled out.
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http://dx.doi.org/10.3390/md18110530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693588PMC
October 2020

Animal and Cellular Studies Demonstrate Some of the Beneficial Impacts of Herring Milt Hydrolysates on Obesity-Induced Glucose Intolerance and Inflammation.

Nutrients 2020 Oct 22;12(11). Epub 2020 Oct 22.

Department of food Sciences and Laboratory of Food Processing and Electromembrane Process (LTAPEM), Université Laval, Québec, QC G1V 0A6, Canada.

The search for bioactive compounds from enzymatic hydrolysates has increased in the last few decades. Fish by-products have been shown to be rich in these valuable molecules; for instance, herring milt is a complex matrix composed of lipids, nucleotides, minerals, and proteins. However, limited information is available on the potential health benefits of this by-product. In this context, three industrial products containing herring milt hydrolysate (HMH) were tested in both animal and cellular models to measure their effects on obesity-related metabolic disorders. Male C57Bl/6J mice were fed either a control chow diet or a high-fat high-sucrose (HFHS) diet for 8 weeks and received either the vehicle (water) or one of the three HMH products (HMH1, HMH2, and HMH3) at a dose of 208.8 mg/kg (representing 1 g/day for a human) by daily oral gavage. The impact of HMH treatments on insulin and glucose tolerance, lipid homeostasis, liver gene expression, and the gut microbiota profile was studied. In parallel, the effects of HMH on glucose uptake and inflammation were studied in L6 myocytes and J774 macrophages, respectively. In vivo, daily treatment with HMH2 and HMH3 improved early time point glycemia during the oral glucose tolerance test (OGTT) induced by the HFHS diet, without changes in weight gain and insulin secretion. Interestingly, we also observed that HMH2 consumption partially prevented a lower abundance of species in the gut microbiota of HFHS diet-fed animals. In addition to this, modulations of gene expression in the liver, such as the upregulation of sucrose nonfermenting AMPK-related kinase (SNARK), were reported for the first time in mice treated with HMH products. While HMH2 and HMH3 inhibited inducible nitric oxide synthase (iNOS) induction in J774 macrophages, glucose uptake was not modified in L6 muscle cells. These results indicate that milt herring hydrolysates reduce some metabolic and inflammatory alterations in cellular and animal models, suggesting a possible novel marine ingredient to help fight against obesity-related immunometabolic disorders.
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http://dx.doi.org/10.3390/nu12113235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690616PMC
October 2020

The fascinating physiology of insulin: celebrating a centennial hormone.

Authors:
André Marette

Am J Physiol Endocrinol Metab 2021 01 26;320(1):E1. Epub 2020 Oct 26.

Department of Medicine, Faculty of Medicine, Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada.

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http://dx.doi.org/10.1152/ajpendo.00496.2020DOI Listing
January 2021

Rhubarb Supplementation Prevents Diet-Induced Obesity and Diabetes in Association with Increased in Mice.

Nutrients 2020 Sep 24;12(10). Epub 2020 Sep 24.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life sciences and BIOtechnology (WELBIO), UCLouvain, Université catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Bruxelles, Belgium.

Obesity and obesity-related disorders, such as type 2 diabetes have been progressively increasing worldwide and treatments have failed to counteract their progression. Growing evidence have demonstrated that gut microbiota is associated with the incidence of these pathologies. Hence, the identification of new nutritional compounds, able to improve health through a modulation of gut microbiota, is gaining interest. In this context, the aim of this study was to investigate the gut-driving effects of rhubarb extract in a context of diet-induced obesity and diabetes. Eight weeks old C57BL6/J male mice were fed a control diet (CTRL), a high fat and high sucrose diet (HFHS) or a HFHS diet supplemented with 0.3% (g/g) of rhubarb extract for eight weeks. Rhubarb supplementation fully prevented HFHS-induced obesity, diabetes, visceral adiposity, adipose tissue inflammation and liver triglyceride accumulation, without any modification in food intake. By combining sequencing and qPCR methods, we found that all these effects were associated with a blooming of , which is strongly correlated with increased expression of in the colon. Our data showed that rhubarb supplementation is sufficient to protect against metabolic disorders induced by a diet rich in lipid and carbohydrates in association with a reciprocal interaction between and Reg3γ.
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http://dx.doi.org/10.3390/nu12102932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601677PMC
September 2020

Berry Polyphenols and Fibers Modulate Distinct Microbial Metabolic Functions and Gut Microbiota Enterotype-Like Clustering in Obese Mice.

Front Microbiol 2020 26;11:2032. Epub 2020 Aug 26.

Institute of Nutrition and Functional Foods (INAF), Faculty of Agriculture and Food Sciences, Laval University, Québec, QC, Canada.

Berries are rich in polyphenols and plant cell wall polysaccharides (fibers), including cellulose, hemicellulose, arabinans and arabino-xyloglucans rich pectin. Most of polyphenols and fibers are known to be poorly absorbed in the small intestine and reach the colon where they interact with the gut microbiota, conferring health benefits to the host. This study assessed the contribution of polyphenol-rich whole cranberry and blueberry fruit powders (CP and BP), and that of their fibrous fractions (CF and BF) on modulating the gut microbiota, the microbial functional profile and influencing metabolic disorders induced by high-fat high-sucrose (HFHS) diet for 8 weeks. Lean mice-associated taxa, including , , and , were selectively induced by diet supplementation with polyphenol-rich CP and BP. Fiber-rich CF also triggered polyphenols-degrading families and . Diet supplementation with polyphenol-rich CP, but not with its fiber-rich CF, reduced fat mass depots, body weight and energy efficiency in HFHS-fed mice. However, CF reduced liver triglycerides in HFHS-fed mice. Importantly, polyphenol-rich CP-diet normalized microbial functions to a level comparable to that of Chow-fed controls. Using multivariate association modeling, taxa and predicted functions distinguishing an obese phenotype from healthy controls and berry-treated mice were identified. The enterotype-like clustering analysis underlined the link between a long-term diet intake and the functional stratification of the gut microbiota. The supplementation of a HFHS-diet with polyphenol-rich CP drove mice gut microbiota from enterotype into an enterotype linked to healthier host status, which is . This study highlights the prebiotic role of polyphenols, and their contribution to the compositional and functional modulation of the gut microbiota, counteracting obesity.
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http://dx.doi.org/10.3389/fmicb.2020.02032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479096PMC
August 2020

Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota.

Open Forum Infect Dis 2020 Sep 11;7(9):ofaa338. Epub 2020 Sep 11.

Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montreal, Québec, Canada.

Background: People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PWH. The antidiabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Nevertheless, it remains unknown whether metformin may benefit PWH receiving ART, especially those with a low CD4/CD8 ratio.

Methods: In the Lilac pilot trial, we recruited 23 nondiabetic PWH receiving ART for more than 2 years with a low CD4/CD8 ratio (<0.7). Blood and stool samples were collected during study visits at baseline, after a 12-week metformin treatment, and 12 weeks after discontinuation. Microbiota composition was analyzed by 16S rDNA gene sequencing, and markers of inflammation were assessed in plasma.

Results: Metformin decreased weight in PWH, and weight loss was inversely correlated with plasma levels of the satiety factor GDF-15. Furthermore, metformin changed the gut microbiota composition by increasing the abundance of anti-inflammatory bacteria such as butyrate-producing species and the protective

Conclusions: Our study provides the first evidence that a 12-week metformin treatment decreased weight and favored anti-inflammatory bacteria abundance in the microbiota of nondiabetic ART-treated PWH. Larger randomized placebo-controlled clinical trials with longer metformin treatment will be needed to further investigate the role of metformin in reducing inflammation and the risk of non-AIDS comorbidities in ART-treated PWH.
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http://dx.doi.org/10.1093/ofid/ofaa338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489545PMC
September 2020

Two polyphenol-rich Brazilian fruit extracts protect from diet-induced obesity and hepatic steatosis in mice.

Food Funct 2020 Oct;11(10):8800-8810

Quebec Heart and Lung Institute, Laval Hospital, Laval University, Quebec City, 2725 Sainte Foy, G1V 4G5, Quebec, Canada.

Consumption of polyphenol-rich food is associated with better metabolic health. Tucum-do-Pantanal (Bactris setosa Mart) and taruma-do-cerrado (Vitex cymosa Bertero ex Spreng) are underexploited native Brazilian fruits with an important source of phytochemicals. In this study, we assessed the effects of 100 mg kg-1 tucum (TPE) and taruma (TCE) extracts on diet-induced obesity (DIO) C57BL/6J mice. After 8 weeks of daily treatment, TPE and TCE were found to significantly prevented the diet-induced body weight gain and fully protected against hepatic steatosis associated with a tendency to stimulate hepatic AMPK phosphorylation. TPE reduced visceral obesity and improved glucose metabolism as revealed by an improvement of the insulin tolerance test, a reduction in the insulin fasting level, and a decreased glucose-induced hyperinsulinemia during an oral glucose tolerance test. TPE and TCE showed promising effects on the treatment of obesity and NAFLD, furthermore, TPE on insulin resistance.
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http://dx.doi.org/10.1039/d0fo01912gDOI Listing
October 2020

Distinct Effects of Milk-Derived and Fermented Dairy Protein on Gut Microbiota and Cardiometabolic Markers in Diet-Induced Obese Mice.

J Nutr 2020 10;150(10):2673-2686

Faculty of Medicine, Laval University, Quebec City, Quebec, Canada.

Background: Recent meta-analyses suggest that the consumption of fermented dairy products reduces type 2 diabetes and cardiovascular disease (CVD) risk, although the underlying mechanisms remain unclear.

Objective: We evaluated whether dairy protein products modulated gut microbiota and cardiometabolic features in mouse models of diet-induced obesity and CVD.

Methods: Eight-week-old C57BL/6J wild-type (WT) and LDLr-/-ApoB100/100 (LRKO) male mice were fed for 12 and 24 wk, respectively, with a high-fat/high-sucrose diet [66% kcal lipids, 22% kcal carbohydrates (100% sucrose), 12% kcal proteins]. The protein sources of the 4 diets were 100% nondairy protein (NDP), or 50% of the NDP energy replaced by milk (MP), milk fermented by Lactobacillus helveticus (FMP), or Greek-style yogurt (YP) protein. Fecal 16S rRNA gene-based amplicon sequencing, intestinal gene expression, and glucose tolerance test were conducted. Hepatic inflammation and circulating adhesion molecules were measured by multiplex assays.

Results: Feeding WT mice for 12 wk led to a 74% increase in body weight, whereas after 24 wk the LRKO mice had a 101.5% increase compared with initial body weight. Compared with NDP and MP, the consumption of FMP and YP modulated the gut microbiota composition in a similar clustering pattern, upregulating the Streptococcus genus in both genotypes. In WT mice, feeding YP compared with NDP increased the expression of genes involved in jejunal (Reg3b, 7.3-fold, P = 0.049) and ileal (Ocln, 1.7-fold, P = 0.047; Il1-β,1.7-fold, P = 0.038; Nos2, 3.8-fold, P = 0.018) immunity and integrity. In LRKO mice, feeding YP compared with MP improved insulin sensitivity by 65% (P = 0.039). In LRKO mice, feeding with FMP versus NDP attenuated hepatic inflammation (monocyte chemoattractant protein 1, 2.1-fold, P ˂ 0.0001; IL1-β, 5.7-fold, P = 0.0003; INF-γ, 1.7-fold, P = 0.002) whereas both FMP [vascular adhesion molecule 1 (VCAM1), 1.3-fold, P = 0.0003] and YP (VCAM1, 1.04-fold, P = 0.013; intracellular adhesion molecule 1, 1.4-fold, P = 0.028) decreased circulating adhesion molecules.

Conclusion: Both fermented dairy protein products reduce cardiometabolic risk factors in diet-induced obese mice, possibly by modulating the gut microbiota.
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http://dx.doi.org/10.1093/jn/nxaa217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549311PMC
October 2020

Sex-differences in echocardiographic assessment of aortic valve in young adult LDLr/ApoB/IGF-II mice.

Exp Gerontol 2020 10 27;140:111075. Epub 2020 Aug 27.

Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada. Electronic address:

Background: LDLr/ApoB/IGF-II mice are used as a calcific aortic valve disease (CAVD) model. However, normal aortic valve hemodynamics i.e. remotely from CAVD onset and the sex-related differences are poorly known.

Methods And Results: Four groups of mice, intact males (IM, n = 49) and females (IF, n = 50), castrated males (CxM, n = 79) and ovariectomized females (OxF: 73), underwent a Doppler-echocardiography at 12 weeks of age. Gonadectomy was performed at 8 weeks. Aortic valve assessment using effective orifice area (EOA, using the continuity equation) and peak aortic transvalvular velocity (V) was feasible in 89% of the mice with good to excellent reliability (intraclass correlation coefficients ranging from 0.90 to 0.98, p < 0.001). Mean V was 104 ± 17 cm/s and mean EOA was 1.18*10 ± 0.22*10 cm. EOA indexed to body surface area was 1.5 ± 0.3 cm/m. The 95th percentile of Vpeak was 132 cm/s and the 5th percentile of indexed EOA was 1.0 cm/m. Interestingly, IM had the highest V (114 ± 14 cm/s) vs each of the other groups (CxM: 106 ± 19 cm/s, OxF: 97 ± 13 cm/s and IF: 96 ± 12 cm/s, ANOVA and corrected p < 0.001). This was mostly explained by a higher stroke volume (ANOVA and corrected p < 0.001) in IM compared to other groups. There were no major sex-differences in ventricular systolic function parameters.

Conclusion: In LDLr/ApoB/IGF-II CAVD mice model, an aortic EOA <0.8*10 cm (or indexed EOA <1.0cm/m), and a peak aortic valve velocity > 132 cm/s may be proposed as thresholds to define CAVD. Intact male mice appear to have higher velocities.
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http://dx.doi.org/10.1016/j.exger.2020.111075DOI Listing
October 2020

Gut microbiota impairs insulin clearance in obese mice.

Mol Metab 2020 12 26;42:101067. Epub 2020 Aug 26.

Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute McMaster University, Hamilton, Ontario, L8N 3Z5, Canada. Electronic address:

Objective: Hyperinsulinemia can be both a cause and consequence of obesity and insulin resistance. Hyperinsulinemia can result from increased insulin secretion and/or reduced insulin clearance. While many studies have focused on mechanisms triggering insulin secretion during obesity, the triggers for changes in insulin clearance during obesity are less defined. In this study, we investigated the role of the microbiota in regulating insulin clearance during diet-induced obesity.

Methods: Blood glucose and insulin clearance were tested in conventional male mice treated with antibiotics and germ-free mice colonized with microbes from mice that were fed a control (chow) diet or an obesogenic high-fat diet (HFD). The composition of the fecal microbiota was analyzed using 16S rRNA sequencing.

Results: Short-term HFD feeding and aging did not alter insulin clearance in the mice. Oral antibiotics mitigated impaired blood insulin clearance in the mice fed an HFD for 12 weeks or longer. Germ-free mice colonized with microbes from HFD-fed donor mice had impaired insulin but not C-peptide clearance. Microbe-transmissible insulin clearance impairment was only observed in germ-free mice after more than 6 weeks post-colonization upon HFD feeding. Five bacterial taxa predicted >90% of the variance in insulin clearance. Mechanistically, impaired insulin clearance was associated with lower levels of hepatic Ceacam-1 but increased liver and skeletal muscle insulin-degrading enzyme (IDE) activity.

Conclusions: Gut microbes regulate insulin clearance during diet-induced obesity. A small cluster of microbes or their metabolites may be targeted for mitigating defects in insulin clearance and hyperinsulinemia during the progression of obesity and type 2 diabetes.
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http://dx.doi.org/10.1016/j.molmet.2020.101067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522491PMC
December 2020

Differential Effects of Chronic Ingestion of Refined Sugars versus Natural Sweeteners on Insulin Resistance and Hepatic Steatosis in a Rat Model of Diet-Induced Obesity.

Nutrients 2020 Jul 30;12(8). Epub 2020 Jul 30.

Quebec Heart and Lung Institute Research Centre, Faculty of Medicine, Laval University, Quebec City, QC G1V 0A6 G1V 4G5, Canada.

While the detrimental effect of refined sugars on health has been the subject of many investigations, little is known about the long-term impact of natural sweeteners on metabolic disorders. In this study we compared the metabolic responses to chronic ingestion of refined sugars compared to various natural sweeteners in diet-induced obese rats. Wistar rats were fed a high-fat high-sucrose diet (HFHS) for 8 weeks and daily gavaged with a solution containing 1 g of total carbohydrates from refined sugar (sucrose or fructose) or six different natural sugar sources, followed by assessment of glucose homeostasis, hepatic lipid accumulation, and inflammation. While glucose tolerance was similar following treatments with refined and natural sugars, lowered glucose-induced hyperinsulinemia was observed with fructose. Consumption of fructose and all-natural sweeteners but not corn syrup were associated with lower insulin resistance as revealed by reduced fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) compared to sucrose treatment of HFHS-fed rats. All-natural sweeteners and fructose induced similar liver lipid accumulation as sucrose. Nevertheless, maple syrup, molasses, agave syrup, and corn syrup as well as fructose further reduced hepatic IL-1β levels compared to sucrose treatment. We conclude that natural sweeteners and especially maple syrup, molasses, and agave syrup attenuate the development of insulin resistance and hepatic inflammation compared to sucrose in diet-induced obese rats, suggesting that consumption of those natural sweeteners is a less harmful alternative to sucrose in the context of obesity.
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http://dx.doi.org/10.3390/nu12082292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469035PMC
July 2020

Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity.

Nat Metab 2020 03 9;2(3):233-242. Epub 2020 Mar 9.

Québec Heart and Lung Research Institute, Laval University, Québec, Québec, Canada.

Visceral obesity is a key risk factor for type 2 diabetes (T2D). Whereas gut dysbiosis appears to be instrumental for this relationship, whether gut-associated signatures translocate to extra-intestinal tissues and how this affects host metabolism remain elusive. Here we provide a comparative analysis of the microbial profile found in plasma, liver and in three distinct adipose tissues of individuals with morbid obesity. We explored how these tissue microbial signatures vary between individuals with normoglycaemia and those with T2D that were matched for body mass index. We identified tissue-specific signatures with higher bacterial load in the liver and omental adipose tissue. Gut commensals, but also environmental bacteria, showed tissue- and T2D-specific compartmentalisation. T2D signatures were most evident in mesenteric adipose tissue, in which individuals with diabetes displayed reduced bacterial diversity concomitant with fewer Gram-positive bacteria, such as Faecalibacterium, as opposed to enhanced levels of typically opportunistic Gram-negative Enterobacteriaceae. Plasma samples of individuals with diabetes were similarly enriched in Enterobacteriaceae, including the pathobiont Escherichia-Shigella. Our work provides evidence for the presence of selective plasma and tissue microbial signatures in individuals with severe obesity and identifies new potential microbial targets and biomarkers of T2D.
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http://dx.doi.org/10.1038/s42255-020-0178-9DOI Listing
March 2020

Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in LDLrApoB mice.

Atherosclerosis 2020 07 24;304:9-21. Epub 2020 May 24.

Quebec Heart and Lung Institute, Department of Medicine, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada; Institute of Nutraceuticals and Functional Foods, Laval University, Quebec City, Quebec, Canada. Electronic address:

Background And Aims: Poor dietary habits contribute to the obesity pandemic and related cardiovascular diseases but the respective impact of high saturated fat versus added sugar consumption remains debated. Herein, we aimed to disentangle the individual role of dietary fat versus sugar in cardiometabolic disease progression.

Methods: We fed pro-atherogenic LDLrApoB mice either a low-fat/high-sucrose (LFHS) or a high-fat/low-sucrose (HFLS) diet for 24 weeks. Weekly body weight gain was registered. 16S rRNA gene-based gut microbial analysis was performed to investigate gut microbial modulations. Intraperitoneal insulin (ipITT) and oral glucose tolerance test (oGTT) were conducted to assess glucose homeostasis and insulin sensitivity. Cytokines were assessed in fasted plasma, epididymal white adipose tissue and liver lysates. Heart function was evaluated by echocardiography. Aortic atheroma lesions were quantified according to the en face technique.

Results: HFLS feeding increased obesity, insulin resistance and dyslipidemia compared to LFHS feeding. Conversely, high sucrose consumption decreased gut microbial diversity while augmenting inflammation and the adaptative immune defense against metabolic endotoxemia and reduced macrophage cholesterol efflux capacity. This led to more severe cardiovascular complications as revealed by remarkably high level of atherosclerotic lesions and the early development of cardiac dysfunction in LFHS vs HFLS fed mice.

Conclusions: We uncoupled obesity-associated insulin resistance from cardiovascular diseases and provided novel evidence that dietary sucrose, not fat, is the main driver of metabolic inflammation accelerating severe atherosclerosis in hyperlipidemic mice.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.05.002DOI Listing
July 2020

Potential therapeutic applications of the gut microbiome in obesity: from brain function to body detoxification.

Int J Obes (Lond) 2020 09 10;44(9):1818-1831. Epub 2020 Jun 10.

Quebec Heart and Lung Institute, and Department of Medicine, Université Laval, Québec, QC, Canada.

The prevalence of obesity is rising every year and associated comorbidities such as cardiovascular diseases are among the leading causes of death worldwide. The gut microbiota has recently emerged as a potential target for therapeutic applications to prevent and treat those comorbidities. In this review, we focus on three conditions related to obesity in which the use of gut microbiota modulators could have benefits; mood disorders, eating behaviors, and body detoxification of persistent organic pollutants (POPs). On one hand, modulation of gut-derived signals to the brain in a context of obesity is involved in the development of neuroinflammation and can subsequently alter behaviors. An altered gut microbiome could change these signals and alleviate their consequences. On the other hand, obesity is associated with an increased accumulation of lipophilic contaminants, such as POPs. Targeting the microbiota could help body detoxication by reducing bioavailability, enhancing degradation by bioremediation or their excretion through the enterohepatic circulation. Thus, a supplementation of prebiotics, probiotics, or synbiotics could represent a complementary strategy to current ones, such as medication and lifestyle modifications, to decrease depression, alter eating behaviors, and lower body burden of pollutants considering the actual obesity epidemic our society is facing.
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http://dx.doi.org/10.1038/s41366-020-0618-3DOI Listing
September 2020

Microbial translocation in type 2 diabetes: when bacterial invaders overcome host defence in human obesity.

Gut 2020 10 9;69(10):1724-1726. Epub 2020 Jun 9.

Department of Medicine, Universite Laval Faculte de medecine, Quebec, Quebec, Canada

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http://dx.doi.org/10.1136/gutjnl-2020-321288DOI Listing
October 2020