Potential novel therapeutic strategies from understanding adipocyte transdifferentiation mechanisms

References

• Dixon JB, le Roux CW, Rubino F, Zimmet P. Bariatric surgery for type 2 diabetes. Lancet 2012;379(9833):2300-11
   PubMed Web of Science ®Google Scholar
• Broeders E, Bouvy ND, Lichtenbelt WD. Endogenous ways to stimulate brown adipose tissue in humans. Ann Med 2014. [Epub ahead of print]
   PubMedGoogle Scholar
• Frontini A, Cinti S. Distribution and development of brown adipocytes in the murine and human adipose organ. Cell Metab 2010;11(4):253-6
   PubMedGoogle Scholar
• Vitali A, Murano I, Zingaretti MC, et al. The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res 2012;53(4):619-29
   PubMed Web of Science ®Google Scholar
• Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014;156(1-2):20-44
   PubMed Web of Science ®Google Scholar
• Nedergaard J, Cannon B. Mammalian hibernation. Philos Trans R Soc Lond B Biol Sci 1990;326(1237):669-85. discussion 85-6
   PubMed Web of Science ®Google Scholar
• Nedergaard J, Golozoubova V, Matthias A, et al. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim Biophys Acta 2001;1504(1):82-106
   PubMed Web of Science ®Google Scholar
• Lowell BB, S-Susulic V, Hamann A, et al. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 1993;366(6457):740-2
   PubMed Web of Science ®Google Scholar
• Rothwell NJ, Stock MJ. A role for brown adipose tissue in diet-induced thermogenesis. Nature 1979;281(5726):31-5
   PubMed Web of Science ®Google Scholar
• Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 2009;9(2):203-9
   PubMed Web of Science ®Google Scholar
• Stanford KI, Middelbeek RJ, Townsend KL, et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 2013;123(1):215-23
   PubMed Web of Science ®Google Scholar
• Bartelt A, Bruns OT, Reimer R, et al. Brown adipose tissue activity controls triglyceride clearance. Nat Med 2011;17(2):200-5
   PubMed Web of Science ®Google Scholar
• Trayhurn P, Nicholls D. Brown adipose tissue. Edward Arnold; London: 1986. p. 1-374
   Google Scholar
• Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360(15):1509-17
   PubMed Web of Science ®Google Scholar
• Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009;360(15):1500-8
   PubMedGoogle Scholar
• Virtanen KA, Lidell ME, Orava J, et al. Functional brown adipose tissue in healthy adults. N Engl J Med 2009;360(15):1518-25
   PubMed Web of Science ®Google Scholar
• Saito M, Okamatsu-Ogura Y, Matsushita M, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 2009;58(7):1526-31
   PubMed Web of Science ®Google Scholar
• Zingaretti MC, Crosta F, Vitali A, 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(9):3113-20
   PubMed Web of Science ®Google Scholar
• Vijgen GH, Bouvy ND, Teule GJ, et al. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab 2012;97(7):E1229-33
   PubMed Web of Science ®Google Scholar
• Ouellet V, Labbe SM, Blondin DP, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 2012;122(2):545-52
   PubMed Web of Science ®Google Scholar
• Ouellet V, Routhier-Labadie A, Bellemare W, et al. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab 2011;96(1):192-9
   PubMed Web of Science ®Google Scholar
• Yoneshiro T, Aita S, Matsushita M, et al. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity 2011;19(1):13-16
   PubMed Web of Science ®Google Scholar
• Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 2013;27(3):234-50
   PubMed Web of Science ®Google Scholar
• Granneman JG, Li P, Zhu Z, Lu Y. Metabolic and cellular plasticity in white adipose tissue I: effects of beta3-adrenergic receptor activation. Am J Physiol Endocrinol Metab 2005;289(4):E608-16
   Google Scholar
• Xue B, Rim JS, Hogan JC, et al. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J Lipid Res 2007;48(1):41-51
   PubMedGoogle Scholar
• Guerra C, Koza RA, Yamashita H, et al. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest 1998;102(2):412-20
   PubMed Web of Science ®Google Scholar
• Himms-Hagen J, Melnyk A, Zingaretti MC, et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am J Physiol Cell Physiol 2000;279(3):C670-81
   Google Scholar
• Loncar D. Convertible adipose tissue in mice. Cell Tissue Res 1991;266(1):149-61
   PubMedGoogle Scholar
• Petrovic N, Walden TB, Shabalina IG, et al. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 2009;285(10):7153-64
   PubMedGoogle Scholar
• Wu J, Bostrom P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012;150(2):366-76
   PubMed Web of Science ®Google Scholar
• Timmons JA, Wennmalm K, Larsson O, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci USA 2007;104(11):4401-6
   PubMedGoogle Scholar
• Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008;454(7207):961-7
   PubMed Web of Science ®Google Scholar
• Sanchez-Gurmaches J, Hung CM, Sparks CA, et al. PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab 2012;16(3):348-62
   PubMed Web of Science ®Google Scholar
• Barbatelli G, Murano I, Madsen L, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 2010;298(6):E1244-53
   Google Scholar
• Lee YH, Petkova AP, Granneman JG. Identification of an adipogenic niche for adipose tissue remodeling and restoration. Cell Metab 2013;18(3):355-67
   PubMedGoogle Scholar
• Rosenwald M, Perdikari A, Rulicke T, Wolfrum C. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 2013;15(6):659-67
   PubMed Web of Science ®Google Scholar
• Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 2013;19(10):1338-44
   PubMed Web of Science ®Google Scholar
• Sharp LZ, Shinoda K, Ohno H, et al. Human BAT possesses molecular signatures that resemble beige/brite cells. PLoS One 2012;7(11):e49452
   PubMed Web of Science ®Google Scholar
• Lidell ME, Betz MJ, Enerback S. Two types of brown adipose tissue in humans. Adipocyte 2014;3(1):63-6
   PubMedGoogle Scholar
• Ussar S, Lee KY, Dankel SN, et al. ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. Sci Transl Med 2014;6(247):247ra103
   PubMedGoogle Scholar
• Cinti S. Between brown and white: novel aspects of adipocyte differentiation. Ann Med 2011;43(2):104-15
   PubMed Web of Science ®Google Scholar
• Morrison SF, Madden CJ, Tupone D. Central neural regulation of brown adipose tissue thermogenesis and energy expenditure. Cell Metab 2014;19(5):741-56
   PubMed Web of Science ®Google Scholar
• Giordano A, Frontini A, Cinti S. Adipose organ nerves revealed by immunohistochemistry. Methods Mol Biol 2008;456:83-95
   PubMedGoogle Scholar
• Villarroya F, Vidal-Puig A. Beyond the sympathetic tone: the new brown fat activators. Cell Metab 2013;17(5):638-43
   PubMedGoogle Scholar
• Kajimura S, Seale P, Spiegelman BM. Transcriptional control of brown fat development. Cell Metab 2010;11(4):257-62
   PubMed Web of Science ®Google Scholar
• Harms MJ, Ishibashi J, Wang W, et al. Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell Metab 2014;19(4):593-604
   PubMed Web of Science ®Google Scholar
• Barneda D, Frontini A, Cinti S, Christian M. Dynamic changes in lipid droplet-associated proteins in the “browning” of white adipose tissues. Biochim Biophys Acta 2013;1831(5):924-33
   PubMedGoogle Scholar
• Contreras GA, Lee YH, Mottillo EP, Granneman JG. Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation. Am J Physiol Endocrinol Metab 2014;307(9):E793-9
   Google Scholar
• Nedergaard J, Bengtsson T, Cannon B. Three years with adult human brown adipose tissue. Ann N Y Acad Sci 2010;1212:E20-36
   Google Scholar
• Cypess AM, White AP, Vernochet C, et al. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med 2013;19(5):635-9
   PubMed Web of Science ®Google Scholar
• Enerback S. Human brown adipose tissue. Cell Metab 2010;11(4):248-52
   PubMed Web of Science ®Google Scholar
• Chondronikola M, Volpi E, Borsheim E, et al. Brown adipose tissue improves whole body glucose homeostasis and insulin sensitivity in humans. Diabetes 2014. [ Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Lans AA, Hoeks J, Brans B, et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest 2013;123(8):3395-403
   PubMedGoogle Scholar
• Vosselman MJ, Brans B, Lans AA, et al. Brown adipose tissue activity after a high-calorie meal in humans. Am J Clin Nutr 2013;98(1):57-64
   PubMed Web of Science ®Google Scholar
• Au-Yong IT, Thorn N, Ganatra R, et al. Brown adipose tissue and seasonal variation in humans. Diabetes 2009;58(11):2583-7
   PubMed Web of Science ®Google Scholar
• Yoneshiro T, Aita S, Matsushita M, et al. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 2013;123(8):3404-8
   PubMedGoogle Scholar
• Frontini A, Vitali A, Perugini J, et al. White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta 2013;1831(5):950-9
   PubMedGoogle Scholar
• Jespersen NZ, Larsen TJ, Peijs L, et al. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metab 2013;17(5):798-805
   PubMed Web of Science ®Google Scholar
• Yoo HS, Qiao L, Bosco C, et al. Intermittent cold exposure enhances fat accumulation in mice. PLoS One 2014;9(5):e96432
   Google Scholar
• Dong M, Yang X, Lim S, et al. Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis. Cell Metab 2013;18(1):118-29
   PubMed Web of Science ®Google Scholar
• Vosselman MJ, Lans AA, Brans B, et al. Systemic beta-adrenergic stimulation of thermogenesis is not accompanied by brown adipose tissue activity in humans. Diabetes 2012;61(12):3106-13
   PubMed Web of Science ®Google Scholar
• Seale P, Conroe HM, Estall J, et al. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 2011;121(1):96-105
   PubMed Web of Science ®Google Scholar
• Christian M, Kiskinis E, Debevec D, et al. RIP140-targeted repression of gene expression in adipocytes. Mol Cell Biol 2005;25(21):9383-91
   PubMedGoogle Scholar
• Scime A, Grenier G, Huh MS, et al. Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1alpha. Cell Metab 2005;2(5):283-95
   PubMedGoogle Scholar
• Cederberg A, Gronning LM, Ahren B, et al. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell 2001;106(5):563-73
   PubMedGoogle Scholar
• Schulz TJ, Huang TL, Tran TT, et al. Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci USA 2011;108(1):143-8
   PubMed Web of Science ®Google Scholar
• Whittle AJ, Carobbio S, Martins L, et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 2012;149(4):871-85
   PubMed Web of Science ®Google Scholar
• Bostrom P, Wu J, Jedrychowski MP, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012;481(7382):463-8
   PubMed Web of Science ®Google Scholar
• Hondares E, Iglesias R, Giralt A, et al. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem 2011;286(15):12983-90
   PubMed Web of Science ®Google Scholar
• Fisher FM, Kleiner S, Douris N, et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 2012;26(3):271-81
   PubMed Web of Science ®Google Scholar
• Yoneshiro T, Saito M. Transient receptor potential activated brown fat thermogenesis as a target of food ingredients for obesity management. Curr Opin Clin Nutr Metab Care 2013;16(6):625-31
   PubMed Web of Science ®Google Scholar
• Bordicchia M, Liu D, Amri EZ, et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest 2012;122(3):1022-36
   PubMed Web of Science ®Google Scholar
• Shabalina IG, Petrovic N, de Jong JM, et al. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Reports 2013;5(5):1196-203
   PubMedGoogle Scholar
• Wu MV, Bikopoulos G, Hung S, Ceddia RB. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high-fat diet and endurance training in rats: Impact on whole-body energy expenditure. J Biol Chem 2014. [Epub ahead of print]
   Google Scholar
• Nedergaard J, Cannon B. How brown is brown fat? It depends where you look. Nat Med 2013;19(5):540-1
   PubMedGoogle Scholar
• Kiskinis E, Chatzeli L, Curry E, et al. RIP140 represses the “brown-in-white” adipocyte program including a futile cycle of triacylglycerol breakdown and synthesis. Mol Endocrinol 2014;28(3):344-56
   PubMedGoogle Scholar
• Tsukiyama-Kohara K, Poulin F, Kohara M, et al. Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1. Nat Med 2001;7(10):1128-32
   PubMed Web of Science ®Google Scholar
• Mori M, Nakagami H, Rodriguez-Araujo G, et al. Essential role for miR-196a in brown adipogenesis of white fat progenitor cells. PLoS Biol 2012;10(4):e1001314
   PubMed Web of Science ®Google Scholar
• Kajimura S, Seale P, Kubota K, et al. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 2009;460(7259):1154-8
   PubMed Web of Science ®Google Scholar
• Nedergaard J, Cannon B. UCP1 mRNA does not produce heat. Biochim Biophys Acta 2013;1831(5):943-9
   PubMed Web of Science ®Google Scholar
• Elabd C, Chiellini C, Carmona M, et al. Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes. Stem Cells 2009;27(11):2753-60
   PubMedGoogle Scholar
• Nishio M, Yoneshiro T, Nakahara M, et al. Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer. Cell Metab 2012;16(3):394-406
   PubMed Web of Science ®Google Scholar
• Borga M, Virtanen KA, Romu T, et al. Brown adipose tissue in humans: detection and functional analysis using PET (positron emission tomography), MRI (magnetic resonance imaging), and DECT (dual energy computed tomography). Methods Enzymol 2014;537:141-59
   PubMed Web of Science ®Google Scholar
• Nedergaard J, Cannon B. The browning of white adipose tissue: some burning issues. Cell Metab 2014;20(3):396-407
   PubMed Web of Science ®Google Scholar