Publications by authors named "Kirsi Virtanen"

95 Publications

The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp-A Study in Finns.

J Clin Med 2021 Mar 23;10(6). Epub 2021 Mar 23.

Turku PET Centre, University of Turku, 20520 Turku, Finland.

The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers of the mutant allele have decreased cerebrocortical response to insulin. Thus, in this study, we addressed whether rs17782313 associates with brain glucose uptake (BGU). Here, [F]-fluorodeoxyglucose positron emission tomography (PET) data from 113 Finnish subjects scanned under insulin clamp conditions who also had the rs17782313 determined were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. Statistical analysis was performed with statistical parametric mapping. There was no difference in age, BMI, and insulin sensitivity as indexed by the M value between the rs17782313-C allele carriers and non-carriers. Brain glucose uptake during insulin clamp was not different by gene allele, and it correlated with the M value, in both the rs17782313-C allele carriers and non-carriers. The obesity risk SNP rs17782313 near the gene is not associated with brain glucose uptake during insulin clamp in humans, and this frequent mutation cannot explain the enhanced brain glucose metabolic rates in insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10061312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004974PMC
March 2021

Changes in electrocardiogram parameters during acute nonshivering cold exposure and associations with brown adipose tissue activity, plasma catecholamine levels, and brachial blood pressure in healthy adults.

Physiol Rep 2021 Feb;9(3):e14718

Turku PET Centre, Turku University Hospital, Turku, Finland.

Background: Sympathetic activity causes changes in electrocardiogram (ECG) during cold exposure and the changes have been studied mostly during hypothermia and less during mild acute nonshivering cold exposure. Cold-induced sympathetic activity also activates brown adipose tissue (BAT) and increases arterial blood pressure (BP) and plasma catecholamine levels. We examined changes in ECG parameters during acute nonshivering cold exposure and their associations with markers of sympathetic activity during cold exposure: brachial blood pressure (BP), plasma catecholamine levels, and BAT activity measured by positron emission tomography (PET).

Methods And Results: Healthy subjects (M/F = 13/24, aged 20-55 years) were imaged with [ O]H O (perfusion, N = 37) and [ F]FTHA to measure plasma nonesterified fatty acid uptake (NEFA uptake, N = 37) during 2-h nonshivering cold exposure. 12-lead ECG (N = 37), plasma catecholamine levels (N = 17), and brachial BP (N = 31) were measured at rest in room temperature (RT) and re-measured after a 2-h nonshivering cold exposure. There were significant differences between RT and cold exposure in P axis (35.6 ± 26.4 vs. 50.8 ± 22.7 degrees, p = 0.005), PR interval (177.7 ± 24.6 ms vs.163.0 ± 28.7 ms, p = 0.001), QRS axis (42.1 ± 31.3 vs. 56.9 ± 24.1, p = 0.003), and QT (411.7 ± 25.5 ms vs. 434.5 ± 39.3 ms, p = 0.001). There was no significant change in HR, QRS duration, QTc, JTc, and T axis during cold exposure. Systolic BP (127.2 ± 15.7 vs. 131.8 ± 17.9 mmHg, p = 0.008), diastolic BP (81.7 ± 12.0 vs. 85.4 ± 13.0 mmHg, p = 0.02), and plasma noradrenaline level increased during cold exposure (1.97 ± 0.61 vs. 5.07 ± 1.32 µmol/L, p = 0.001). Cold-induced changes in ECG parameters did not correlate with changes in BAT activity, brachial BP, plasma catecholamines, or skin temperature.

Conclusions: During short-term nonshivering cold exposure, there were increases in P axis, PR interval, QRS axis, and QT compared to RT in healthy adults. Cold-induced changes in ECG parameters did not correlate with BAT activity, brachial BP, or plasma catecholamine levels which were used as markers of cold-induced sympathetic activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881801PMC
February 2021

Differential mitochondrial gene expression in adipose tissue following weight loss induced by diet or bariatric surgery.

J Clin Endocrinol Metab 2021 Feb 9. Epub 2021 Feb 9.

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland.

Context: Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.

Objective: Investigate how SAT mitochondria change following diet-induced and bariatric surgery-induced weight-loss interventions in four independent weight-loss studies.

Design/setting: The DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n=261) and 6-month weight maintenance (n=121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n=172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in two studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n=19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n=49) and 5-year (n=37) follow-up.

Results: Diet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; Ingenuity Pathway Analyses (IPA) z-scores: -8.7 following LCD, -4.4 following weight maintenance; CRYO: IPA z-score: -5.6, all p<0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, p<0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, p<0.001).

Conclusions: Differentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab072DOI Listing
February 2021

The FADS1 Genotype Modifies Metabolic Responses to the Linoleic Acid and Alpha-linolenic Acid Containing Plant Oils-Genotype Based Randomized Trial FADSDIET2.

Mol Nutr Food Res 2021 04 3;65(7):e2001004. Epub 2021 Mar 3.

Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland.

Scope: The article investigates the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha-linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and of markers of low-grade inflammation and glucose-insulin homeostasis.

Methods And Results: One-hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8-week intervention with either LA- or ALA-enriched diet (13 E% PUFA). The source of LA and ALA are 30-50 mL of sunflower oil (SFO, 62-63% LA) and Camelina sativa oil (CSO, 30- are randomized to an 35% ALA), respectively. In the SFO arm, there is a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p < 0.001), disposition index (DI ) (p = 0.039), and for serum high-sensitive c-reactive protein (hs-CRP, p = 0.029) after excluding the participants with hs-CRP concentration of >10 mg L and users of statins or anti-inflammatory therapy. In the CSO arm, there are significant genotype x diet interactions for n-3 polyunsaturated fatty acids, but not for the clinical characteristics.

Conclusions: The FADS1 genotype modifies the response to high PUFA diets, especially to high-LA diet. These findings suggest that approaches considering FADS variation may be useful in personalized dietary counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mnfr.202001004DOI Listing
April 2021

Associations Between Brain Gray Matter Volumes and Adipose Tissue Metabolism in Healthy Adults.

Obesity (Silver Spring) 2021 Mar 2;29(3):543-549. Epub 2021 Feb 2.

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.

Objective: Gray matter (GM) volume in different brain loci has been shown to vary in obesity and diabetes, and elevated fasting plasma nonesterified fatty acid (NEFA) levels have been suggested as one potential mechanism. The hypothesis presented in this study is that brown adipose tissue (BAT) activity may correlate with GM volume in areas negatively associated with obesity and diabetes.

Methods: A total of 36 healthy patients (M/F: 12/24, age 39.7 ± 9.4 years, BMI 27.5 ± 5.6 kg/m ) were imaged with positron emission tomography using fatty acid analog [ F]FTHA to measure NEFA uptake and with [ O]H O to measure perfusion during cold exposure, at room temperature during fasting, or during a postprandial state. A 2-hour hyperinsulinemic euglycemic clamp was performed to measure whole-body insulin sensitivity (M value, mean 7.6 ± 3.9 mg/kg/min). T1-weighted magnetic resonance imaging at 1.5 T was performed on all patients.

Results: BAT NEFA uptake was associated directly with GM volume in anterior cerebellum and occipital lobe (P ≤ 0.04) when adjusted for age, gender, and intra-abdominal fat volume and with anterior cerebellum, limbic lobe, and temporal lobe GM volumes when adjusted for M value.

Conclusions: BAT NEFA metabolism may participate in protection from cognitive degeneration associated with cardiometabolic risk factors, such as central obesity and insulin resistance. Potential causal relationships between BAT activity and GM volumes remain to be examined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/oby.23094DOI Listing
March 2021

Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort.

Diabetes Care 2021 Mar 14;44(3):788-794. Epub 2021 Jan 14.

Turku PET Centre, University of Turku, Turku, Finland

Objective: Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of study participants across a wide range of age and insulin sensitivity.

Research Design And Methods: [F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 participants scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acid levels, C-reactive protein levels, HbA, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling.

Results: Insulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin-resistant participants BGU was enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with additional increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein and free fatty acid levels, sex, and HbA were not associated with BGU.

Conclusions: In this large cohort of participants of either sex across a wide range of age and insulin sensitivity, insulin sensitivity was the best predictor of BGU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-1549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896252PMC
March 2021

Exercise intensity regulates cytokine and klotho responses in men.

Nutr Diabetes 2021 01 7;11(1). Epub 2021 Jan 7.

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.

Background: Short-term exercise training programs that consist of moderate intensity endurance training or high intensity interval training have become popular choices for healthy lifestyle modifications, with as little as two weeks of training being shown to improve cardiorespiratory fitness and whole-body glucose metabolism. An emerging concept in exercise biology is that exercise stimulates the release of cytokines and other factors into the blood that contribute to the beneficial effects of exercise on metabolism, but whether these factors behave similarly in response to moderate and high intensity short term training is not known. Here, we determined the effects of two short-term exercise training programs on the concentrations of select secreted cytokines and Klotho, a protein involved in anti-aging.

Methods: Healthy, sedentary men (n = 22) were randomized to moderate intensity training (MIT) or sprint intensity training (SIT) treatment groups. SIT consisted of 6 sessions over 2 weeks of 6 × 30 s all out cycle ergometer sprints with 4 min of recovery between sprints. MIT consisted of 6 sessions over 2 weeks of cycle ergometer exercise at 60% VO, gradually increasing in duration from 40 to 60 min. Blood was taken before the intervention and 48 h after the last training session, and glucose uptake was measured using [F]FDG-PET/CT scanning. Cytokines were measured by multiplex and Klotho concentrations by ELISA.

Results: Both training protocols similarly increased VO and decreased fat percentage and visceral fat (P < 0.05). MIT and SIT training programs both reduced the concentrations of IL-6, Hepatocyte Growth Factor (HGF) and Leptin. Interestingly, MIT, but not SIT increased monocyte chemoattractant protein-1 (MCP-1) concentrations, an exercise-induced cytokine, as well as Klotho concentrations.

Conclusion: Short-term exercise training at markedly different intensities similarly improves cardiovascular fitness but results in intensity-specific changes in cytokine responses to exercise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41387-020-00144-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791135PMC
January 2021

Short Dietary Intervention with Olive Oil Increases Brown Adipose Tissue Activity in Lean but not Overweight Subjects.

J Clin Endocrinol Metab 2021 Jan;106(2):472-484

Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Background: The brown adipose tissue (BAT) is a potential target for the treatment of obesity and metabolic disorders. Its activation by cold exposure or adrenergic drugs can increase systemic insulin sensitivity and improve lipid metabolism; however, little is known about the effects of specific dietary components on BAT activity.

Objectives: We asked if a short-term (4 weeks) dietary intervention with olive oil could modify BAT activity in lean and overweight/obese volunteers.

Design: This was a 4-week open clinical trial in which all participants underwent a dietary intervention with extra-virgin olive oil supplementation. As the initial intake of olive oil was controlled all the participants were controls of themselves.

Results: The intervention resulted in significant increase in blood monounsaturated fatty acid levels, which was accompanied by increased BAT activity in lean but not in overweight/obese volunteers. In the lean group, an increase in leptin was detected after the intervention, and low leptin values at the beginning of the study were predictive of greater BAT activity after intervention. In addition, increase in leptin concentration was associated with increased BAT activity. Three known endogenous mediators of BAT activity, secretin, fibroblast growth factor 21 (FGF21), and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were increased by intervention in lean, whereas only secretin and FGF21 were increased in subjects with excessive weight.

Conclusion: This study provides clinical evidence for the impact of monounsaturated fatty acids on BAT activity and an advance in the understanding of the beneficial health effects of olive oil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa824DOI Listing
January 2021

Exercise training improves adipose tissue metabolism and vasculature regardless of baseline glucose tolerance and sex.

BMJ Open Diabetes Res Care 2020 08;8(1)

Turku PET Centre, University of Turku, Turku, Finland

Introduction: We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex.

Research Design And Methods: 26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4-6×30 s at maximum effort) and MICT (40-60 min at 60% of maximal aerobic capacity (VO)). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation.

Results: Training increased glucose uptake in VAT (p<0.001) and femoral SAT (p<0.001) and decreased fatty acid uptake in VAT (p=0.01) irrespective of baseline glucose tolerance and sex. In IR participants, training increased adipose tissue vasculature and decreased CD36 and ANGPTL4 gene expression in abdominal SAT. SIT was superior in increasing VO and VAT glucose uptake in the IR group, whereas MICT reduced VAT fatty acid uptake more than SIT.

Conclusions: Short-term training improves adipose tissue metabolism both in healthy and IR participants independently of the sex. Adipose tissue angiogenesis and gene expression was only significantly affected in IR participants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjdrc-2019-000830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437884PMC
August 2020

Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training.

J Clin Endocrinol Metab 2020 12;105(12)

Turku PET Centre, University of Turku, Turku, Finland.

Context: Exercise training improves bone mineral density, but little is known about the effects of training on bone marrow (BM) metabolism. BM insulin sensitivity has been suggested to play an important role in bone health and whole-body insulin sensitivity.

Objective: To study the effects of exercise training on BM metabolism.

Design: Randomized controlled trial.

Setting: Clinical research center.

Participants: Sedentary healthy (n = 28, 40-55 years, all males) and insulin resistant (IR) subjects (n = 26, 43-55 years, males/females 16/10).

Intervention: Two weeks of sprint interval training or moderate-intensity continuous training.

Main Outcome Measures: We measured femoral, lumbar, and thoracic BM insulin-stimulated glucose uptake (GU) and fasting free fatty acid uptake (FFAU) using positron-emission tomography and bone turnover markers from plasma.

Results: At baseline, GU was highest in lumbar, followed by thoracic, and lowest in femoral BM (all Ps < 0.0001). FFAU was higher in lumbar and thoracic than femoral BM (both Ps < 0.0001). BM FFAU and femoral BM GU were higher in healthy compared to IR men and in females compared to males (all Ps < 0.05). Training increased femoral BM GU similarly in all groups and decreased lumbar BM FFAU in males (all Ps < 0.05). Osteocalcin and PINP were lower in IR than healthy men and correlated positively with femoral BM GU and glycemic status (all Ps < 0.05).

Conclusions: BM metabolism differs regarding anatomical location. Short-term training improves BM GU and FFAU in healthy and IR subjects. Bone turnover rate is decreased in insulin resistance and associates positively with BM metabolism and glycemic control.

Clinical Trial Registration Number: NCT01344928.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526736PMC
December 2020

Brain substrate metabolism and ß-cell function in humans: A positron emission tomography study.

Endocrinol Diabetes Metab 2020 Jul 19;3(3):e00136. Epub 2020 Apr 19.

Turku PET Centre University of Turku Turku Finland.

Aims: Recent clinical studies have shown enhanced brain glucose uptake during clamp and brain fatty acid uptake in insulin-resistant individuals. Preclinical studies suggest that the brain may be involved in the control of insulin secretion. The aim of this study was to investigate whether brain metabolism assessed as brain glucose and fatty acid uptake is associated with the parameters of β-cell function in humans.

Materials And Methods: We analysed cross-sectional data of 120 subjects across a wide range of BMI and insulin sensitivity. Brain glucose uptake (BGU) was measured during euglycaemic-hyperinsulinaemic clamp (n = 67) and/or during fasting (n = 45) using [F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). In another group of subjects (n = 34), brain fatty acid uptake was measured using [F]-fluoro-6-thia-heptadecanoic acid (FTHA) PET during fasting. The parameters of βcell function were derived from OGTT modelling. Statistical analysis was performed with whole-brain voxel-based statistical parametric mapping.

Results: In non-diabetics, BGU during euglycaemic hyperinsulinaemic clamp correlated positively with basal insulin secretion rate ( = 0.51,  = .0008) and total insulin output ( = 0.51,  = .0008), whereas no correlation was found in type 2 diabetics. BGU during clamp correlated positively with potentiation in non-diabetics ( = 0.33,  = .02) and negatively in type 2 diabetics ( = -0.61,  = .02). The associations in non-diabetics were not explained with whole-body insulin sensitivity or BMI. No correlations were found between baseline (fasting) BGU and basal insulin secretion rate, whereas baseline brain fatty acid uptake correlated directly with basal insulin secretion rate ( = 0.39,  = .02) and inversely with potentiation ( = -0.36,  = .04).

Conclusions: Our study provides coherent, though correlative, evidence that, in humans, the brain may be involved in the control of insulin secretion independently of insulin sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/edm2.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375082PMC
July 2020

Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice.

Nat Metab 2019 08 19;1(8):830-843. Epub 2019 Aug 19.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

Human and rodent brown adipose tissues (BAT) appear morphologically and molecularly different. Here we compare human BAT with both classical brown and brite/beige adipose tissues of 'physiologically humanized' mice: middle-aged mice living under conditions approaching human thermal and nutritional conditions, that is, prolonged exposure to thermoneutral temperature (approximately 30 °C) and to an energy-rich (high-fat, high-sugar) diet. We find that the morphological, cellular and molecular characteristics (both marker and adipose-selective gene expression) of classical brown fat, but not of brite/beige fat, of these physiologically humanized mice are notably similar to human BAT. We also demonstrate, both in silico and experimentally, that in physiologically humanized mice only classical BAT possesses a high thermogenic potential. These observations suggest that classical rodent BAT is the tissue of choice for translational studies aimed at recruiting human BAT to counteract the development of obesity and its comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42255-019-0101-4DOI Listing
August 2019

Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity.

Cell Metab 2020 Jul 25;32(1):56-70.e7. Epub 2020 Jun 25.

Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany. Electronic address:

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2020.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437516PMC
July 2020

Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot.

J Clin Endocrinol Metab 2020 07;105(7)

Institute of Biomedicine, University of Turku, Turku, Finland.

Context: Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans.

Objective: Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM).

Design: This was a cross-sectional and longitudinal study.

Setting: The study was conducted in a clinical research center.

Patients Or Other Participants: Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty.

Intervention(s): Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point.

Main Outcome Measure: We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR.

Results: Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue.

Conclusions: Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247553PMC
July 2020

Predicting Skeletal Muscle and Whole-Body Insulin Sensitivity Using NMR-Metabolomic Profiling.

J Endocr Soc 2020 Apr 11;4(4):bvaa026. Epub 2020 Mar 11.

Turku PET Centre, University of Turku, Turku, Finland.

Purpose: Abnormal lipoprotein and amino acid profiles are associated with insulin resistance and may help to identify this condition. The aim of this study was to create models estimating skeletal muscle and whole-body insulin sensitivity using fasting metabolite profiles and common clinical and laboratory measures.

Material And Methods: The cross-sectional study population included 259 subjects with normal or impaired fasting glucose or type 2 diabetes in whom skeletal muscle and whole-body insulin sensitivity (M-value) were measured during euglycemic hyperinsulinemic clamp. Muscle glucose uptake (GU) was measured directly using [F]FDG-PET. Serum metabolites were measured using nuclear magnetic resonance (NMR) spectroscopy. We used linear regression to build the models for the muscle GU (Muscle-insulin sensitivity index [ISI]) and M-value (whole-body [WB]-ISI). The models were created and tested using randomly selected training (n = 173) and test groups (n = 86). The models were compared to common fasting indices of insulin sensitivity, homeostatic model assessment-insulin resistance (HOMA-IR) and the revised quantitative insulin sensitivity check index (QUICKI).

Results: WB-ISI had higher correlation with actual M-value than HOMA-IR or revised QUICKI ( = 0.83 vs -0.67 and 0.66;  < 0.05 for both comparisons), whereas the correlation of Muscle-ISI with the actual skeletal muscle GU was not significantly stronger than HOMA-IR's or revised QUICKI's ( = 0.67 vs -0.58 and 0.59; both nonsignificant) in the test dataset.

Conclusion: Muscle-ISI and WB-ISI based on NMR-metabolomics and common laboratory measurements from fasting serum samples and basic anthropometrics are promising rapid and inexpensive tools for determining insulin sensitivity in at-risk individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jendso/bvaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093091PMC
April 2020

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue.

Front Endocrinol (Lausanne) 2020 21;11:73. Epub 2020 Feb 21.

Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.

Metabolites of omega-6 and omega-3 polyunsaturated fatty acids are important signaling molecules implicated in the control of adipogenesis and energy balance regulation. Some of these metabolites belonging to the group of oxylipins have been associated with non-shivering thermogenesis in mice mediated by brown or brite adipose tissue. We aimed to identify novel molecules with thermogenic potential and to clarify the relevance of these findings in a translational context. Therefore, we characterized and compared the oxylipin profiles of murine and human adipose tissues with different abundance of brown or brite adipocytes. A broad panel of 36 fatty acid metabolites was quantified in brown and white adipose tissues of C57BL/6J mice acclimatized to different ambient temperatures and in biopsies of human supraclavicular brown and white adipose tissue. The oxylipin profile of murine brite adipose tissue was not distinguishable from white adipose tissue, suggesting that adipose tissue browning is not associated with major changes in the oxylipin metabolism. Human brown and white adipose tissue also exhibited similar metabolite profiles. This is in line with previous studies proposing human brown adipose tissue to resemble the nature of murine brite adipose tissue representing a heterogeneous mixture of brite and white adipocytes. Although the global oxylipin profile served as a marker for the abundance of thermogenic adipocytes in bona fide brown but not white adipose tissue, we identified 5-HETE and 5,6-EET as individual compounds consistently associated with the abundance of brown or brite adipocytes in human BAT and murine brite fat. Further studies need to establish whether these candidates are mere markers or functional effectors of thermogenic capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046592PMC
March 2021

High Brown Fat Activity Correlates With Cardiovascular Risk Factor Levels Cross-Sectionally and Subclinical Atherosclerosis at 5-Year Follow-Up.

Arterioscler Thromb Vasc Biol 2020 05 16;40(5):1289-1295. Epub 2020 Jan 16.

From the Turku PET Centre, Turku University Hospital, Finland (J.R., J.O., K.A.V.).

Objective: Brown adipose tissue (BAT) activity correlates negatively with obesity and insulin resistance, and BAT has been suggested to act as a protective factor against atherogenesis. We aimed to examine subclinical atherosclerosis and risk factor levels in a group of individuals who had 5 years earlier participated in positron-emission tomography studies with measurements of BAT activity. Approach and Results: Study cohort (males/females=5/26, baseline age 41.4±7.9 years; body mass index, 26.8±6.3 kg/m) underwent positron-emission tomography imaging at baseline with [F] FDG (glucose uptake) and [O] HO (perfusion) to measure BAT activity during cold exposure. At 5-year follow-up, ultrasound was performed to measure carotid intima-media thickness, carotid distensibility (a marker of arterial elasticity), and brachial flow-mediated dilation (an estimate of endothelial function). Fasting plasma lipids and hemoglobin A1c were measured from venous samples at baseline and at follow-up. Median values were used as cut points for high cold-induced BAT activity (BAT glucose uptake >2.40 μmoL/100 g per minute and perfusion >8.4 mL/100 g per minute). Baseline cold-induced BAT glucose uptake and perfusion correlated directly with carotid distensibility and inversely with mean bulbus intima-media thickness and maximum intima-media thickness ( always ≤0.02). Baseline body mass index, plasma triglycerides, and HbA1c correlated negatively with BAT glucose uptake and perfusion in cold ( always ≤0.048). Correlations between cold-induced BAT activity, cardiovascular risk factors, and atherosclerosis were attenuated with corrections for multiple comparisons.

Conclusions: Cold-induced BAT activity at baseline seems to correlate with lower levels of conventional cardiovascular risk factors at baseline and with lower carotid intima-media thickness and higher carotid elasticity at 5-year follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.119.313806DOI Listing
May 2020

Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia.

Med Sci Sports Exerc 2020 01;52(1):94-104

Turku PET Centre, University of Turku, Turku, FINLAND.

Introduction: Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance.

Methods: Twenty-six, sedentary subjects (prediabetic, n = 9; type 2 diabetes, n = 17; age, 49 [SD, 4] yr; body mass index, 30.5 [SD, 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using positron emission tomography. Gut microbiota composition was analyzed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit.

Results: V˙O2peak improved only after SIT (P = 0.01). Both training modes reduced systematic and intestinal inflammatory markers (tumor necrosis factor-α, lipopolysaccharide binding protein) (time P < 0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time P = 0.03) and decreasing Firmicutes/Bacteroidetes ratio (time P = 0.04). Moreover, there was a decrease in Clostridium genus (time P = 0.04) and Blautia (time P = 0.051). Only MICT decreased jejunal FAU (P = 0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus.

Conclusions: Intestinal substrate uptake associates with gut microbiota composition and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1249/MSS.0000000000002112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028471PMC
January 2020

Specific loss of adipocyte CD248 improves metabolic health via reduced white adipose tissue hypoxia, fibrosis and inflammation.

EBioMedicine 2019 Jun 17;44:489-501. Epub 2019 Jun 17.

Centre for Blood Research, Life Sciences Institute, Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address:

Background: A positive energy balance promotes white adipose tissue (WAT) expansion which is characterized by activation of a repertoire of events including hypoxia, inflammation and extracellular matrix remodelling. The transmembrane glycoprotein CD248 has been implicated in all these processes in different malignant and inflammatory diseases but its potential impact in WAT and metabolic disease has not been explored.

Methods: The role of CD248 in adipocyte function and glucose metabolism was evaluated by omics analyses in human WAT, gene knockdowns in human in vitro differentiated adipocytes and by adipocyte-specific and inducible Cd248 gene knockout studies in mice.

Findings: CD248 is upregulated in white but not brown adipose tissue of obese and insulin-resistant individuals. Gene ontology analyses showed that CD248 expression associated positively with pro-inflammatory/pro-fibrotic pathways. By combining data from several human cohorts with gene knockdown experiments in human adipocytes, our results indicate that CD248 acts as a microenvironmental sensor which mediates part of the adipose tissue response to hypoxia and is specifically perturbed in white adipocytes in the obese state. Adipocyte-specific and inducible Cd248 knockouts in mice, both before and after diet-induced obesity and insulin resistance/glucose intolerance, resulted in increased microvascular density as well as attenuated hypoxia, inflammation and fibrosis without affecting fat cell volume. This was accompanied by significant improvements in insulin sensitivity and glucose tolerance.

Interpretation: CD248 exerts detrimental effects on WAT phenotype and systemic glucose homeostasis which may be reversed by suppression of adipocyte CD248. Therefore, CD248 may constitute a target to treat obesity-associated co-morbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.05.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606747PMC
June 2019

Effects of short-term sprint interval and moderate-intensity continuous training on liver fat content, lipoprotein profile, and substrate uptake: a randomized trial.

J Appl Physiol (1985) 2019 06 18;126(6):1756-1768. Epub 2019 Apr 18.

Turku PET Centre, University of Turku , Turku , Finland.

Type 2 diabetes (T2D) and increased liver fat content (LFC) alter lipoprotein profile and composition and impair liver substrate uptake. Exercise training mitigates T2D and reduces LFC, but the benefits of different training intensities in terms of lipoprotein classes and liver substrate uptake are unclear. The aim of this study was to evaluate the effects of moderate-intensity continuous training (MICT) or sprint interval training (SIT) on LFC, liver substrate uptake, and lipoprotein profile in subjects with normoglycemia or prediabetes/T2D. We randomized 54 subjects (normoglycemic group, = 28; group with prediabetes/T2D, = 26; age = 40-55 yr) to perform either MICT or SIT for 2 wk and measured LFC with magnetic resonance spectroscopy, lipoprotein composition with NMR, and liver glucose uptake (GU) and fatty acid uptake (FAU) using PET. At baseline, the group with prediabetes/T2D had higher LFC, impaired lipoprotein profile, and lower whole body insulin sensitivity and aerobic capacity compared with the normoglycemic group. Both training modes improved aerobic capacity ( < 0.001) and lipoprotein profile (reduced LDL and increased large HDL subclasses; all < 0.05) with no training regimen (SIT vs. MICT) or group effect (normoglycemia vs. prediabetes/T2D). LFC tended to be reduced in the group with prediabetes/T2D compared with the normoglycemic group posttraining ( = 0.051). When subjects were divided according to LFC (high LFC, >5.6%; low LFC, <5.6%), training reduced LFC in subjects with high LFC ( = 0.009), and only MICT increased insulin-stimulated liver GU ( = 0.03). Short-term SIT and MICT are effective in reducing LFC in subjects with fatty liver and in improving lipoprotein profile regardless of baseline glucose tolerance. Short-term MICT is more efficient in improving liver insulin sensitivity compared with SIT. In the short term, both sprint interval training and moderate-intensity continuous training (MICT) reduce liver fat content and improve lipoprotein profile; however, MICT seems to be preferable in improving liver insulin sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/japplphysiol.00900.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620664PMC
June 2019

Intramyocellular lipid accumulation after sprint interval and moderate-intensity continuous training in healthy and diabetic subjects.

Physiol Rep 2019 02;7(3):e13980

Turku PET Centre, University of Turku, Turku, Finland.

The effects of sprint interval training (SIT) on intramyocellular (IMCL) and extramyocellular (EMCL) lipid accumulation are unclear. We tested the effects of SIT and moderate-intensity continuous training (MICT) on IMCL and EMCL accumulation in a randomized controlled setting in two different study populations; healthy untrained men (n 28) and subjects with type 2 diabetes (T2D) or prediabetes (n 26). Proton magnetic resonance spectroscopy ( H MRS) was used to determine IMCL and EMCL in the Tibialis anterior muscle (TA) before and after a 2-week exercise period. The exercise period comprised six sessions of SIT or MICT cycling on a cycle ergometer. IMCL increased after SIT compared to MICT (P = 0.042) in both healthy and T2D/prediabetic subjects. On EMCL the training intervention had no significant effect. In conclusion, IMCL serves as an important energy depot during exercise and can be extended by high intensity exercise. The effects of high intensity interval exercise on IMCL seem to be similar regardless of insulin sensitivity or the presence of T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.13980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369060PMC
February 2019

Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation.

Cell 2018 11 15;175(6):1561-1574.e12. Epub 2018 Nov 15.

Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, Freising, Germany. Electronic address:

The molecular mediator and functional significance of meal-associated brown fat (BAT) thermogenesis remains elusive. Here, we identified the gut hormone secretin as a non-sympathetic BAT activator mediating prandial thermogenesis, which consequentially induces satiation, thereby establishing a gut-secretin-BAT-brain axis in mammals with a physiological role of prandial thermogenesis in the control of satiation. Mechanistically, meal-associated rise in circulating secretin activates BAT thermogenesis by stimulating lipolysis upon binding to secretin receptors in brown adipocytes, which is sensed in the brain and promotes satiation. Chronic infusion of a modified human secretin transiently elevates energy expenditure in diet-induced obese mice. Clinical trials with human subjects showed that thermogenesis after a single-meal ingestion correlated with postprandial secretin levels and that secretin infusions increased glucose uptake in BAT. Collectively, our findings highlight the largely unappreciated function of BAT in the control of satiation and qualify BAT as an even more attractive target for treating obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2018.10.016DOI Listing
November 2018

BATLAS: Deconvoluting Brown Adipose Tissue.

Cell Rep 2018 10;25(3):784-797.e4

Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland. Electronic address:

Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2018.09.044DOI Listing
October 2018

Adipose tissue and skeletal muscle insulin-mediated glucose uptake in insulin resistance: role of blood flow and diabetes.

Am J Clin Nutr 2018 10;108(4):749-758

Turku PET Centre, University of Turku, Turku, Finland.

Background: Adipose tissue glucose uptake is impaired in insulin-resistant states, but ex vivo studies of human adipose tissue have yielded heterogeneous results. This discrepancy may be due to different regulation of blood supply.

Objective: The aim of this study was to test the flow dependency of in vivo insulin-mediated glucose uptake in fat tissues, and to contrast it with that of skeletal muscle.

Design: We reanalyzed data from 159 individuals in which adipose tissue depots-subcutaneous abdominal and femoral, and intraperitoneal-and femoral skeletal muscle were identified by MRI, and insulin-stimulated glucose uptake ([18F]-fluoro-2-deoxyglucose) and blood flow ([15O]-H2O) were measured simultaneously by positron emission tomography scanning.

Results: Individuals in the bottom tertile of whole-body glucose uptake [median (IQR) 36 (17) µmol. kg fat-free mass (kgFFM)-1 . min-1 .nM-1] displayed all features of insulin resistance compared with the rest of the group [median (IQR) 97 (71) µmol . kgFFM-1 .min-1 . nM-1]. Rates of glucose uptake were directly related to the degree of insulin resistance in all fat depots as well as in skeletal muscle. However, blood flow was inversely related to insulin sensitivity in each fat depot (all P ≤ 0.03), whereas femoral muscle blood flow was not significantly different between insulin-resistant and insulin-sensitive subjects, and was not related to insulin sensitivity. Furthermore, in subjects performing one-leg exercise, blood flow increased 5- to 6-fold in femoral muscle but not in the overlying adipose tissue. The presence of diabetes was associated with a modest increase in fat and muscle glucose uptake independent of insulin resistance.

Conclusions: Reduced blood supply is an important factor for the impairment of in vivo insulin-mediated glucose uptake in both subcutaneous and visceral fat. In contrast, the insulin resistance of glucose uptake in resting skeletal muscle is predominantly a cellular defect. Diabetes provides a modest compensatory increase in fat and muscle glucose uptake that is independent of insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqy162DOI Listing
October 2018

Correction to: Regulation of human brown adipose tissue by adenosine and A receptors - studies with [O]HO and [C]TMSX PET/CT.

Eur J Nucl Med Mol Imaging 2018 11;45(12):2244

Turku PET Centre, University of Turku, P.O. Box 52, FI-20520, Turku, Finland.

The original version of this article contained a mistake in the first sentence of the Results section of the Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-018-4144-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828304PMC
November 2018

Activation of Human Brown Adipose Tissue (BAT): Focus on Nutrition and Eating.

Authors:
Kirsi A Virtanen

Handb Exp Pharmacol 2019 ;251:349-357

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.

Brown adipose tissue activation occurs most effectively by cold exposure. In the modern world, we do not spend long periods in cold environment, and eating and meals may be other activators of brown fat function. Short-term regulation of brown fat functional activity by eating involves most importantly insulin. Insulin is capable to increase glucose uptake in human brown adipose tissue fivefold to fasting conditions. Oxidative metabolism in brown fat is doubled both by cold and by a meal. Human brown adipose tissue is an insulin-sensitive tissue type, and insulin resistance impairs the function, as is found in obesity. Body weight reduction improves cold-induced activation of human brown adipose tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/164_2018_136DOI Listing
July 2019

Brown Adipose Tissue Energy Metabolism in Humans.

Front Endocrinol (Lausanne) 2018 7;9:447. Epub 2018 Aug 7.

Department of Nuclear Medicine and Radiobiology, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC, Canada.

The demonstration of metabolically active brown adipose tissue (BAT) in humans primarily using positron emission tomography coupled to computed tomography (PET/CT) with the glucose tracer 18-fluorodeoxyglucose (FDG) has renewed the interest of the scientific and medical community in the possible role of BAT as a target for the prevention and treatment of obesity and type 2 diabetes (T2D). Here, we offer a comprehensive review of BAT energy metabolism in humans. Considerable advances in methods to measure BAT energy metabolism, including nonesterified fatty acids (NEFA), chylomicron-triglycerides (TG), oxygen, Krebs cycle rate, and intracellular TG have led to very good quantification of energy substrate metabolism volume of active BAT . These studies have also shown that intracellular TG are likely the primary energy source of BAT upon activation by cold. Current estimates of BAT's contribution to energy expenditure range at the lower end of what would be potentially clinically relevant if chronically sustained. Yet, FDG PET/CT remains the gold-standard defining method to quantify total BAT volume of activity, used to calculate BAT's total energy expenditure. Unfortunately, BAT glucose metabolism better reflects BAT's insulin sensitivity and blood flow. It is now clear that most glucose taken up by BAT does not fuel mitochondrial oxidative metabolism and that BAT glucose uptake can therefore be disconnected from thermogenesis. Furthermore, BAT thermogenesis is efficiently recruited upon repeated cold exposure, doubling to tripling its total oxidative capacity, with reciprocal reduction of muscle thermogenesis. Recent data suggest that total BAT volume may be much larger than the typically observed 50-150 ml with FDG PET/CT. Therefore, the current estimates of total BAT thermogenesis, largely relying on total BAT volume using FDG PET/CT, may underestimate the true contribution of BAT to total energy expenditure. Quantification of the contribution of BAT to energy expenditure begs for the development of more integrated whole body methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2018.00447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090055PMC
August 2018

Small Intestinal Length Associates with Serum Triglycerides Before and After LRYGB.

Obes Surg 2018 12;28(12):3969-3975

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210, Kuopio, Finland.

Background And Aims: Different bariatric procedures have been associated with variable weight loss and decrease in serum levels of lipids and lipoproteins. This variation could be partly related to the length of the small intestinal bypass. We evaluated the association of the small intestinal length with the non-alcoholic fatty liver disease (NAFLD) at baseline and with lipid metabolism before and after laparoscopic Roux-en-Y gastric bypass (LRYGB).

Methods: Seventy consecutive morbidly obese patients were recruited to this prospective study. A standard 60-cm biliopancreatic limb (BPL) and 120-cm alimentary limb (AL) was performed, and thereafter, the common channel (CC) length was measured during elective LRYGB. Histological analysis of liver biopsy to diagnose NAFLD was performed. The mRNA expression of genes participating in the cholesterol and fatty acid metabolism in the liver was analyzed.

Results: Female sex (p = 0.006), serum triglycerides (TG, p = 0.016), serum alanine aminotransferase (ALT, p = 0.007), and liver steatosis (p = 0.001) associated with the small intestinal length (BPL + AL + CC) at baseline. Association remained significant between levels of serum TG and CC length (p = 0.048) at 1-year follow-up. Liver mRNA expression of genes regulating cholesterol synthesis and bile metabolism did not associate with the baseline small intestinal length.

Conclusions: Our findings support the suggestions that small intestinal length regulates TG metabolism before and after LRYGB. Therefore, modification of the length of bypassed small intestine based on measured total small intestinal length could optimize the outcomes of the elective LRYGB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11695-018-3447-xDOI Listing
December 2018