[Frontiers in Bioscience 16, 1233-1260, January 1, 2011]

Brown fat biology and thermogenesis

Denis Richard1, Frederic Picard1

1 Quebec Heart And Lung Institute Research Center and Laval University Interdisciplinary Group In Obesity Research, 2725 Chemin Sainte-Foy, Quebec G1V 4G5 Canada


1. Abstract
2. Introduction: overview of brown fat
3. The biology of the brown adipocyte
3.1. PPARg and PGC1a are key regulators of brown fat cell differentiation
3.2. Brown adipocytes in classical BAT depots emerge from dermomyotome cells
3.3. PRDM16 induces brown fat from a myoblastic lineage
3.4. UCP1-expressing cells in WAT could emerge from varied origins
4. UCP1
4.1. UCP1 has evolved as the only thermogenic UCP
4.2. UCPI confers BAT its extraordinary thermogenic power
4.3. UCP1 is a nucleotide-sensitive metabolic uncoupler
4.4. UCP1 expression is controlled at the transcriptional level
5. BAT, energy balance regulation and obesity
5.1. SNS-mediated thermogenesis is a determinant of energy expenditure
6. The control of SNS-mediated BAT thermogenesis 6.1. The preoptic area (POA), dorsomedial hypothalamus (DMH), rostral ventromedial medulla (RVM) govern thermoregulatory thermogenesis 6.2. Most energy-balance-regulation centers modulate SNS-mediated BAT thermogenesis
6.3. The ventral hypothalamus coordinates BAT-mediated energy expenditure
6.4. The melanocortin system is a major actor in SNS-mediated BAT thermogenesis
6.5. Do brain UCP2-expressing neurons modulate BAT UCP1 activity?
6.6. The activity of the ventral hypothalamus neurons is influenced by peripheral hormones
6.7. The melanin-concentrating-hormone (MCH) system suppresses BAT thermogenesis
6.8. The endocannabinoid system also controls BAT thermogenesis
7. BAT in humans
7.1. Cervical and supraclavicular fat areas taking up 18F-FDG correspond to true BAT depots 7.2. Outdoor temperature, age, sex, body mass index, and diabetic status determine the detection / prevalence of 18F-FDG uptake in BAT in humans
7.3. Low environmental temperature increases BAT 18F-FDG uptake
7.4. Sex influences the detection of 18F-FDG BAT
7.5. 18F-FDG BAT is more prevalent in young subjects
7.6. The prevalence, mass and glucose uptake activity of 18F-FDG BAT decreases with the increase in adiposity
7.7. 18F-FDG BAT is less prevalent in diabetic patients and barely detectable following the b-adrenergic blockade
7.8. BAT thermogenesis could be an important energy-dissipating process in humans
8. Concluding remarks
9. References


Brown fat (brown adipose tissue, BAT) primary function is to produce heat. There is now compelling evidence to indicate that brown fat cells in some BAT depots share their predecessor cells with myocytes. Brown adipocyte (trans)differentiation depends on various receptors / transcription factors that include peroxisome proliferator-activated receptor g (PPARgamma), PPARgamma-coactivator-1alpha (PGC1alpha), PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM16), CCAAT/enhancer-binding protein (C/EBP-beta) and bone morphogenetic protein 7 (BMP7). Such mediators also help BAT to acquire its thermogenic phenotype, which is essentially conferred by uncoupling protein 1 (UCP1). UCP1 uncouples adenosine-5'-triphosphate (ATP) synthesis from substrate oxidation in brown adipocytes. Its activity depends on the availability of fatty acids delivered upon BAT's beta)-adrenergic activation, which, physiologically, ensues from the sympathetic nervous system (SNS) activation of the tissue. SNS-mediated thermogenesis is largely controlled by the hypothalamus and brainstem. Recently, positron emission tomography / computed tomography (PET/CT) scanning investigations have revealed the presence in adult humans of important neck and shoulder BAT depots. That finding has contributed to reinstate a strong interest for brown adipocyte biology and thermogenesis. This review aims at the unique biology of BAT with the emphasis put on the recent discoveries regarding the brown adipocyte development and function.