33
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Brown Adipose Tissue Energy Metabolism in Humans

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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 ( 18FDG) 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 per volume of active BAT in vivo. 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, 18FDG 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 18FDG PET/CT. Therefore, the current estimates of total BAT thermogenesis, largely relying on total BAT volume using 18FDG 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 in vivo methods.

          Related collections

          Most cited references195

          • Record: found
          • Abstract: found
          • Article: not found

          Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans.

          Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Recent studies using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with 11C-acetate, 18FDG, and 18F-fluoro-thiaheptadecanoic acid (18FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat.

            Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige-fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial creatine kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole-body energy expenditure after administration of a β3-agonist and reduces beige and brown adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PAPERCLIP.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes.

              The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of "brown adipocytes" within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional "brown-like" adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C(-/-) mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote "browning" of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                07 August 2018
                2018
                : 9
                : 447
                Affiliations
                [1] 1Division of Endocrinology, Department of Medicine, Centre de Recherche du CHUS, Université de Sherbrooke , Sherbrooke, QC, Canada
                [2] 2Faculty of Medicine, University of Ottawa , Ottawa, ON, Canada
                [3] 3Turku PET Centre, Turku University Hospital , Turku, Finland
                [4] 4Institute of Public Health and Clinical Nutrition, University of Eastern Finland (UEF) , Kuopio, Finland
                [5] 5Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval , Quebec City, QC, Canada
                [6] 6Faculty of Health Sciences, University of Ottawa , Ottawa, ON, Canada
                [7] 7Department of Nuclear Medicine and Radiobiology, Centre de Recherche du CHUS, Université de Sherbrooke , Sherbrooke, QC, Canada
                Author notes

                Edited by: Mohamed Abu-Farha, Dasman Diabetes Institute, Kuwait

                Reviewed by: Krzysztof W. Nowak, Poznan University of Life Sciences, Poland; Michaela Tencerova, University of Southern Denmark Odense, Denmark

                *Correspondence: André C. Carpentier andre.carpentier@ 123456usherbrooke.ca

                This article was submitted to Diabetes, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2018.00447
                6090055
                30131768
                08a69c4c-0f44-4220-81cb-b359ec61945a
                Copyright © 2018 Carpentier, Blondin, Virtanen, Richard, Haman and Turcotte.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 May 2018
                : 20 July 2018
                Page count
                Figures: 8, Tables: 1, Equations: 0, References: 256, Pages: 21, Words: 19161
                Funding
                Funded by: Canadian Diabetes Association 10.13039/100007476
                Funded by: Canadian Institutes of Health Research 10.13039/501100000024
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                brown adipose tissue,energy metabolism,obesity,type 2 diabetes,molecular imaging,positron emission tomography,tracer methods

                Comments

                Comment on this article