Brown fat fuel utilization and thermogenesis

Trends in Endocrinology and Metabolism

Volumn 25, Issue 4, 2014, Pages 168-177

  Townsend, Kristy L ^a   Tseng, Yu Hua ^a,b  

^a JOSLIN DIABETES CENTER   (United States)

^b HARVARD STEM CELL INSTITUTE   (United States)

Author keywords

Brown adipose tissue; Energy expenditure; Uncoupling protein 1

Indexed keywords

ACYL COENZYME A; ACYLGLYCEROL LIPASE; CD36 ANTIGEN; CHYLOMICRON; DIACYLGLYCEROL; FAT DROPLET; FATTY ACID; FATTY ACID TRANSPORTER; FATTY ACID TRANSPORTER 1; FATTY ACID TRANSPORTER 4; G PROTEIN COUPLED RECEPTOR; GLUCOSE; GLUCOSE TRANSPORTER 1; GLUCOSE TRANSPORTER 4; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HORMONE SENSITIVE LIPASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; LIPOPROTEIN LIPASE; MONOACYLGLYCEROL; PALMITOYL COENZYME A HYDROLASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; SMOOTHENED PROTEIN; THYROXINE; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; VASCULOTROPIN B; VERY LOW DENSITY LIPOPROTEIN;

ADIPOCYTE; ADRENERGIC ACTIVITY; BROWN ADIPOSE TISSUE; CELL MEMBRANE; COLD EXPOSURE; ENERGY EXPENDITURE; ENZYME INDUCTION; ESTERIFICATION; FAT MASS; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; GENE EXPRESSION; GLUCOSE TOLERANCE; GLUCOSE TRANSPORT; GLUCOSE UTILIZATION; GLYCOLYSIS; HUMAN; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTERNALIZATION; LIPID STORAGE; LIPOGENESIS; LIPOLYSIS; MITOCHONDRION; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN TRANSPORT; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; SUBCUTANEOUS FAT; THERMOGENESIS; VASCULARIZATION; WHITE ADIPOSE TISSUE; ANIMAL; ENERGY METABOLISM; LIPID METABOLISM; METABOLISM; PHYSIOLOGY;

ADIPOSE TISSUE, BROWN; ANIMALS; ENERGY METABOLISM; GLUCOSE; HUMANS; LIPID METABOLISM; THERMOGENESIS;

EID: 84897095375     PISSN: 10432760     EISSN: 18793061     Source Type: Journal    
DOI: 10.1016/j.tem.2013.12.004     Document Type: Review

References (112)

1. Townsend K.L., Tseng Y.H. Brown adipose tissue: recent insights into development, metabolic function, and therapeutic potential. Adipocyte 2012, 1:13-24.
2. Hany T.F., et al. Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur. J. Nucl. Med. Mol. Imaging 2002, 29:1393-1398.
3. Nedergaard J., et al. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 2007, 293:E444-E452.
4. Cypess A.M., et al. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 2009, 360:1509-1517.
5. Marken Lichtenbelt W.D., et al. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 2009, 360:1500-1508.
6. Virtanen K.A., et al. Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 2009, 360:1518-1525.
7. Zingaretti M.C., et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009, 23:3113-3120.
8. Saito M., et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 2009, 58:1526-1531.
9. Orava J., et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 2011, 14:272-279.
10. Ouellet V., et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J. Clin. Invest. 2012, 122:545-552.
11. Yoneshiro T., et al. Recruited brown adipose tissue as an antiobesity agent in humans. J. Clin. Invest. 2013, 123:3404-3408.
12. van der Lans A.A., et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J. Clin. Invest. 2013, 123:3395-3403.
13. Enerback S. The origins of brown adipose tissue. N. Engl. J. Med. 2009, 360:2021-2023.
14. Ishibashi J., Seale P. Medicine. Beige can be slimming. Science 2010, 328:1113-1114.
15. Petrovic N., et al. Chronic PPARγ activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classical brown adipocytes. J. Biol. Chem. 2009, 285:7152-7164.
16. Villarroya J., et al. An endocrine role for brown adipose tissue?. Am. J. Physiol. Endocrinol. Metab. 2013, 305:E567-E572.
17. Schulz T.J., Tseng Y.H. Brown adipose tissue: development, metabolism and beyond. Biochem. J. 2013, 453:167-178.
18. Harms M., Seale P. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 2013, 19:1252-1263.
19. Bartelt A., et al. Brown adipose tissue activity controls triglyceride clearance. Nat. Med. 2011, 17:200-205.
20. Yu X.X., et al. Cold elicits the simultaneous induction of fatty acid synthesis and beta-oxidation in murine brown adipose tissue: prediction from differential gene expression and confirmation in vivo. FASEB J. 2002, 16:155-168.
21. Shimizu Y., et al. Effects of noradrenaline on the cell-surface glucose transporters in cultured brown adipocytes: Novel mechanism for selective activation of GLUT1 glucose transporters. Biochem. J. 1998, 330:397-403.
22. Williams K.J., Fisher E.A. Globular warming: how fat gets to the furnace. Nat. Med. 2011, 17:157-159.
23. Nedergaard J., et al. New powers of brown fat: fighting the metabolic syndrome. Cell Metab. 2011, 13:238-240.
24. Vallerand A.L., et al. Cold exposure potentiates the effect of insulin on in vivo glucose uptake. Am. J. Physiol. 1987, 253:E179-E186.
25. Skarulis M.C., et al. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J. Clin. Endocrinol. Metab. 2010, 95:256-262.
26. Teperino R., et al. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat. Cell 2012, 151:414-426.
27. de Jesus L.A., et al. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J. Clin. Invest. 2001, 108:1379-1385.
28. Christoffolete M.A., et al. Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis. Diabetes 2004, 53:577-584.
29. Marsili A., et al. Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity. PLoS ONE 2011, 6:e20832.
30. Stanford K.I., et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J. Clin. Invest. 2013, 123:215-223.
31. Liu X., et al. Brown adipose tissue transplantation improves whole-body energy metabolism. Cell Res. 2013, 23:851-854.
32. Gunawardana S.C., Piston D.W. Reversal of type 1 diabetes in mice by brown adipose tissue transplant. Diabetes 2012, 61:674-682.
33. de Souza C.J., et al. CL-316,243, a beta3-specific adrenoceptor agonist, enhances insulin-stimulated glucose disposal in nonobese rats. Diabetes 1997, 46:1257-1263.
34. Glatz J.F., et al. Membrane fatty acid transporters as regulators of lipid metabolism: implications for metabolic disease. Physiol. Rev. 2010, 90:367-417.
35. Vinolo M.A., et al. G-protein-coupled receptors as fat sensors. Curr. Opin. Clin. Nutr. Metab. Care 2012, 15:112-116.
36. Lass A., et al. Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Prog. Lipid Res. 2011, 50:14-27.
37. Roberts J.L., et al. Brown adipose tissue triacylglycerol fatty acids of obese and lean mice: in situ and in transplants. Lipids 1986, 21:195-201.
38. Kanda T., et al. PPARgamma in the endothelium regulates metabolic responses to high-fat diet in mice. J. Clin. Invest. 2009, 119:110-124.
39. Hagberg C.E., et al. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Nature 2012, 490:426-430.
40. Villanueva C.J., et al. Adipose subtype-selective recruitment of TLE3 or Prdm16 by PPARgamma specifies lipid storage versus thermogenic gene programs. Cell Metab. 2013, 17:423-435.
41. Hoy A.J., et al. Adipose triglyceride lipase-null mice are resistant to high-fat diet-induced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation. Endocrinology 2011, 152:48-58.
42. Liang W.C., Nishino I. Lipid storage myopathy. Curr. Neurol. Neurosci. Rep. 2011, 11:97-103.
43. Ahmadian M., et al. Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype. Cell Metab. 2011, 13:739-748.
44. Goldberg I.J., et al. Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways. J. Lipid Res. 2009, 50(Suppl.):S86-S90.
45. Wang H., Eckel R.H. Lipoprotein lipase: from gene to obesity. Am. J. Physiol. Endocrinol. Metab. 2009, 297:E271-E288.
46. Rader D.J., Tall A.R. The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis?. Nat. Med. 2012, 18:1344-1346.
47. Dong M., et al. Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis. Cell Metab. 2013, 18:118-129.
48. Fitzgibbons T.P., et al. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. Am. J. Physiol. Heart Circ. Physiol. 2011, 301:H1425-H1437.
49. Duivenvoorden I., et al. Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice. Diabetes 2005, 54:664-671.
50. Bartelt A., et al. Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning. Biochim. Biophys. Acta 2013, 1831:934-942.
51. Davies B.S., et al. Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across endothelial cells. J. Lipid Res. 2012, 53:2690-2697.
52. Young S.G., et al. GPIHBP1, an endothelial cell transporter for lipoprotein lipase. J. Lipid Res. 2011, 52:1869-1884.
53. Beigneux A.P., et al. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons. Cell Metab. 2007, 5:279-291.
54. Davies B.S., et al. GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries. Cell Metab. 2010, 12:42-52.
55. Weinstein M.M., et al. Reciprocal metabolic perturbations in the adipose tissue and liver of GPIHBP1-deficient mice. Arterioscler. Thromb. Vasc. Biol. 2012, 32:230-235.
56. Tvrdik P., et al. Cig30, a mouse member of a novel membrane protein gene family, is involved in the recruitment of brown adipose tissue. J. Biol. Chem. 1997, 272:31738-31746.
57. Westerberg R., et al. ELOVL3 is an important component for early onset of lipid recruitment in brown adipose tissue. J. Biol. Chem. 2006, 281:4958-4968.
58. Zadravec D., et al. Ablation of the very-long-chain fatty acid elongase ELOVL3 in mice leads to constrained lipid storage and resistance to diet-induced obesity. FASEB J. 2010, 24:4366-4377.
59. Lodhi I.J., et al. Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARgamma activation to decrease diet-induced obesity. Cell Metab. 2012, 16:189-201.
60. Bartelt A., et al. A new, powerful player in lipoprotein metabolism: brown adipose tissue. J. Mol. Med. (Berl.) 2012, 90:887-893.
61. Cao H., et al. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 2008, 134:933-944.
62. Eissing L., et al. De novo lipogenesis in human fat and liver is linked to ChREBP-beta and metabolic health. Nat. Commun. 2013, 4:1528.
63. Iizuka K., et al. Feedback looping between ChREBP and PPARalpha in the regulation of lipid metabolism in brown adipose tissues. Endocr. J. 2013, 60:1145-1153.
64. Liu S., et al. A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid use. Nature 2013, 502:550-554.
65. Silva J.E. Thyroid hormone control of thermogenesis and energy balance. Thyroid 1995, 5:481-492.
66. Cypess A.M., et al. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:10001-10005.
67. Bokor S., et al. Single-nucleotide polymorphism of CD36 locus and obesity in European adolescents. Obesity (Silver Spring) 2010, 18:1398-1403.
68. Wu Q., et al. Fatty acid transport protein 1 is required for nonshivering thermogenesis in brown adipose tissue. Diabetes 2006, 55:3229-3237.
69. Martin C., et al. The lipid-sensor candidates CD36 and GPR120 are differentially regulated by dietary lipids in mouse taste buds: impact on spontaneous fat preference. PLoS ONE 2011, 6:e24014.
70. Furuhashi M., Hotamisligil G.S. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat. Rev. Drug Discov. 2008, 7:489-503.
71. Yamamoto T., et al. Quantitative evaluation of the effects of cold exposure of rats on the expression levels of ten FABP isoforms in brown adipose tissue. Biotechnol. Lett. 2011, 33:237-242.
72. Yamashita H., et al. Induction of fatty acid-binding protein 3 in brown adipose tissue correlates with increased demand for adaptive thermogenesis in rodents. Biochem. Biophys. Res. Commun. 2008, 377:632-635.
73. Shan T., et al. Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues. FASEB J. 2013, 27:277-287.
74. Zhang Y., et al. Targeted deletion of thioesterase superfamily member 1 promotes energy expenditure and protects against obesity and insulin resistance. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:5417-5422.
75. Ji S., et al. Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse. Mol. Genet. Metab. 2008, 93:314-322.
76. Doh K.O., et al. Interrelation between long-chain fatty acid oxidation rate and carnitine palmitoyltransferase 1 activity with different isoforms in rat tissues. Life Sci. 2005, 77:435-443.
77. Hauton D., et al. The role of the liver in lipid metabolism during cold acclimation in non-hibernator rodents. Comp. Biochem. Physiol. B: Biochem. Mol. Biol. 2006, 144:372-381.
78. Hauton D., et al. Both substrate availability and utilisation contribute to the defence of core temperature in response to acute cold. Comp. Biochem. Physiol. A: Mol. Integr. Physiol. 2009, 154:514-522.
79. Wymann M.P., Schneiter R. Lipid signalling in disease. Nat. Rev. Mol. Cell Biol. 2008, 9:162-176.
80. Collins S., et al. Positive and negative control of Ucp1 gene transcription and the role of beta-adrenergic signaling networks. Int. J. Obes. (Lond.) 2010, 34(Suppl. 1):S28-S33.
81. Mottillo E.P., et al. Lipolytic products activate peroxisome proliferator-activated receptor (PPAR) alpha and delta in brown adipocytes to match fatty acid oxidation with supply. J. Biol. Chem. 2012, 287:25038-25048.
82. Laplante M., et al. PPAR-gamma activation mediates adipose depot-specific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion. Diabetes 2003, 52:291-299.
83. Festuccia W.T., et al. Depot-specific effects of the PPARgamma agonist rosiglitazone on adipose tissue glucose uptake and metabolism. J. Lipid Res. 2009, 50:1185-1194.
84. Girousse A., Langin D. Adipocyte lipases and lipid droplet-associated proteins: insight from transgenic mouse models. Int. J. Obes. (Lond.) 2012, 36:581-594.
85. Barneda D., et al. Dynamic changes in lipid droplet-associated proteins in the 'browning' of white adipose tissues. Biochim. Biophys. Acta 2013, 1831:924-933.
86. Zhou Z., et al. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat. Genet. 2003, 35:49-56.
87. Shimizu T., Yokotani K. Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA fragmentation factor-alpha-like effector A, in rat interscapular brown adipose tissue by sympathetically activated beta3-adrenoreceptors. Biochem. Biophys. Res. Commun. 2009, 387:294-299.
88. Hallberg M., et al. A functional interaction between RIP140 and PGC-1alpha regulates the expression of the lipid droplet protein CIDEA. Mol. Cell. Biol. 2008, 28:6785-6795.
89. Puri V., et al. Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage. J. Biol. Chem. 2007, 282:34213-34218.
90. Toh S.Y., et al. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice. PLoS ONE 2008, 3:e2890.
91. Sawada T., et al. Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype. PLoS ONE 2010, 5:e14006.
92. Miyoshi H., et al. Perilipin overexpression in mice protects against diet-induced obesity. J. Lipid Res. 2010, 51:975-982.
93. Villarroya F., Vidal-Puig A. Beyond the sympathetic tone: the new brown fat activators. Cell Metab. 2013, 17:638-643.
94. Ueta C.B., et al. beta(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice. J. Endocrinol. 2012, 214:359-365.
95. Krief S., et al. Tissue distribution of beta 3-adrenergic receptor mRNA in man. J. Clin. Invest. 1993, 91:344-349.
96. Collins S. ß-adrenoceptor signaling networks in adipocytes for recruiting stored fat and energy expenditure. Front. Endocrinol. (Lausanne) 2012, 2:102.
97. Carey A.L., et al. Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia 2013, 56:147-155.
98. Townsend K.L., et al. Increased mitochondrial activity in BMP7-treated brown adipocytes, due to increased CPT1- and CD36-mediated fatty acid uptake. Antioxid. Redox Signal. 2012, 19:243-257.
99. Hondares E., et al. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J. Biol. Chem. 2011, 286:12983-12990.
100. Fisher F.M., et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 2012, 26:271-281.
101. Virtue S., Vidal-Puig A. It's not how fat you are, it's what you do with it that counts. PLoS Biol. 2008, 6:e237.
102. Geisler J.G. Targeting energy expenditure via fuel switching and beyond. Diabetologia 2011, 54:237-244.
103. Ukropcova B., et al. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle. Diabetes 2007, 56:720-727.
104. Virtue S., et al. A new role for lipocalin prostaglandin d synthase in the regulation of brown adipose tissue substrate utilization. Diabetes 2012, 61:3139-3147.
105. Fedorenko A., et al. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 2012, 151:400-413.
106. Cannon B., Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 2004, 84:277-359.
107. de Meis L., et al. Brown adipose tissue mitochondria: modulation by GDP and fatty acids depends on the respiratory substrates. Biosci. Rep. 2012, 32:53-59.
108. Divakaruni A.S., et al. Fatty acids change the conformation of uncoupling protein 1 (UCP1). J. Biol. Chem. 2012, 287:36845-36853.
109. Rothwell N.J., Stock M.J. A role for brown adipose tissue in diet-induced thermogenesis. Nature 1979, 281:31-35.
110. Feldmann H.M., et al. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009, 9:203-209.
111. Schlogl M., et al. Overfeeding over 24 hours does not activate brown adipose tissue in humans. J. Clin. Endocrinol. Metab. 2013, 98:E1956-E1960.
112. Kozak L.P. Brown fat and the myth of diet-induced thermogenesis. Cell Metab. 2010, 11:263-267.