Heterogeneity of white adipose tissue: molecular basis and clinical implications DOI Creative Commons
Kelvin H. M. Kwok,

Karen S.L. Lam,

Aimin Xu

et al.

Experimental & Molecular Medicine, Journal Year: 2016, Volume and Issue: 48(3), P. e215 - e215

Published: March 11, 2016

Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic proliferative capacity, glucose lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability vascularization. Additional factors that influence adipose are genetic predisposition, environment, gender age. Under obese condition, these depot-specific translate into specific fat distribution patterns, which closely associated with differential cardiometabolic risks. For instance, individuals central obesity more susceptible to developing diabetes cardiovascular complications, whereas those peripheral metabolically healthy. This review summarizes the clinical mechanistic evidence for give rise metabolic consequences, provides therapeutic insights targeted treatment of obesity. Investigations needed variety white deposits body on obesity-related health problems. Aimin Xu colleagues at University Hong Kong reviewed current understanding (fat) how it behaves parts body. known be diverse composition, its properties depending large cells become where they accumulate People 'central obesity'—extensive abdominal region—are likely develop heart problems, example. researchers call further research examining associations between risks hope therapies targeting tissues might possibility.

Language: Английский

Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans DOI Creative Commons
Maria Chondronikola, Elena Volpi, Elisabet Børsheim

et al.

Cell Metabolism, Journal Year: 2016, Volume and Issue: 23(6), P. 1200 - 1206

Published: May 28, 2016

Language: Английский

Citations

294
Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity DOI Open Access
Alana O’Mara, James W. Johnson,

Joyce D. Linderman

et al.

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(5), P. 2209 - 2219

Published: Jan. 21, 2020

BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women diverse ethnicities (27.5 ± 1.1 years age, BMI 25.4 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) 4 weeks in an open-label study. The primary endpoint was change BAT activity as measured [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, glucose metabolism assessed frequently sampled intravenous tolerance test.RESULTSChronic therapy increased activity. Whole-body REE higher, without changes body weight or composition. Additionally, there were elevations levels beneficial lipoprotein biomarkers HDL ApoA1, well total bile acids. Adiponectin, WAT-derived hormone has antidiabetic antiinflammatory capabilities, acute 35% higher upon completion Finally, test revealed sensitivity, effectiveness, secretion.CONCLUSIONThese findings indicate human can be after chronic pharmacological stimulation support investigation disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work supported grants from Intramural Research Program NIDDK, NIH (DK075112, DK075116, DK071013, DK071014).

Language: Английский

Citations

292
Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans DOI Open Access

Mark J. W. Hanssen,

Anouk A.J.J. van der Lans,

Boudewijn Brans

et al.

Diabetes, Journal Year: 2015, Volume and Issue: 65(5), P. 1179 - 1189

Published: Dec. 30, 2015

Recruitment of brown adipose tissue (BAT) has emerged as a potential tool to combat obesity and associated metabolic complications. Short-term cold acclimation been shown not only enhance the presence activity BAT in lean humans but also improve profile skeletal muscle benefit glucose uptake patients with type 2 diabetes. Here we examined whether short-term induced such adaptations 10 metabolically healthy obese male subjects. A 10-day period resulted increased cold-induced BAT, assessed by [18F]fluorodeoxyglucose positron emission tomography/computed tomography. was negatively related age, similar trend for body fat percentage. In addition, positively visceral white tissue, although subcutaneous depots unchanged upon acclimation. Cold-induced tended increase acclimation, which paralleled basal GLUT4 localization sarcolemma, through biopsies. Proximal skin temperature subjective responses were slightly improved at end period. These prolonged exposure mild may lead metabolism or prevent development obesity-associated insulin resistance hyperglycemia.

Language: Английский

Citations

274
Brown Adipose Tissue Energy Metabolism in Humans DOI Creative Commons
André C. Carpentier, Denis P. Blondin,

Kirsi A. Virtanen

et al.

Frontiers in Endocrinology, Journal Year: 2018, Volume and Issue: 9

Published: Aug. 7, 2018

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

Language: Английский

Citations

270
Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue DOI Creative Commons
Renate Schreiber, Clemens Diwoky, Gabriele Schoiswohl

et al.

Cell Metabolism, Journal Year: 2017, Volume and Issue: 26(5), P. 753 - 763.e7

Published: Oct. 11, 2017

Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by triglyceride lipase (ATGL) is considered a key step NST. Accordingly, the severe cold intolerance global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Here we show that this conclusion incorrect. We demonstrate although BAT-specific loss impairs lipolysis alters morphology, it does not compromise β3-adrenergic thermogenic response or cold-induced Instead, NST depends on nutrient supply white during fasting, suggesting circulating energy substrates are sufficient Cold AKO caused dysfunction as previously suspected but cardiomyopathy. conclude functional requires adequate substrate cardiac function, depend ATGL-mediated BAT.

Language: Английский

Citations

269
Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): Recommendations for Standardized FDG-PET/CT Experiments in Humans DOI Creative Commons
Kong Y. Chen, Aaron M. Cypess, Maren R. Laughlin

et al.

Cell Metabolism, Journal Year: 2016, Volume and Issue: 24(2), P. 210 - 222

Published: Aug. 1, 2016

Language: Английский

Citations

268
Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis DOI
Anna Worthmann,

Clara John,

Malte Rühlemann

et al.

Nature Medicine, Journal Year: 2017, Volume and Issue: 23(7), P. 839 - 849

Published: June 12, 2017

Language: Английский

Citations

256
Body temperature regulation in diabetes DOI Creative Commons
Glen P. Kenny, Ronald J. Sigal,

Ryan McGinn

et al.

Temperature, Journal Year: 2016, Volume and Issue: 3(1), P. 119 - 145

Published: Jan. 2, 2016

The effects of type 1 and 2 diabetes on the body's physiological response to thermal stress is a relatively new topic in research. Diabetes tends place individuals at greater risk for heat-related illness during heat waves physical activity due an impaired capacity dissipate heat. Specifically, with have been reported lower skin blood flow sweating responses exposure this can important consequences cardiovascular regulation glycemic control. Those who are particularly vulnerable include poor control affected by diabetes-related complications. On other hand, good maintenance aerobic fitness often delay complications possibly impairments loss. Despite this, it alarming note lack information regarding given vulnerability population. In contrast, few studies examined cold exception its therapeutic potential, diabetes. This review summarizes current state knowledge impact respect core temperature regulation, adjustments while also considering beneficial maintaining fitness.

Language: Английский

Citations

246
The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases DOI Open Access
Jae Ho Lee, Anna Park, Kyoung‐Jin Oh

et al.

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(19), P. 4924 - 4924

Published: Oct. 4, 2019

: Mitochondria play a key role in maintaining energy homeostasis metabolic tissues, including adipose tissues. The two main types of tissues are the white tissue (WAT) and brown (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for expenditure by non-shivering thermogenesis through mitochondria. response to appropriate stimuli such as cold exposure β-adrenergic agonist undergoes browning wherein it acts BAT, which characterized presence higher number Mitochondrial dysfunction adipocytes has been reported have strong correlation with diseases, obesity type 2 diabetes. Dysfunction mitochondria results detrimental effects on adipocyte differentiation, lipid metabolism, insulin sensitivity, oxidative capacity, thermogenesis, consequently lead diseases. Recent studies shown that mitochondrial function can be improved using thiazolidinedione, mitochondria-targeted antioxidants, dietary natural compounds; performing exercise; controlling caloric restriction, thereby inducing adaptive WAT. In this review, we focus summarize molecular regulation involved improvement so strategies developed treat

Language: Английский

Citations

238
Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus DOI
Matthijs K. C. Hesselink, Vera B. Schrauwen‐Hinderling, Patrick Schrauwen

et al.

Nature Reviews Endocrinology, Journal Year: 2016, Volume and Issue: 12(11), P. 633 - 645

Published: July 22, 2016

Language: Английский

Citations

219