Profile
International Journal of Clinical Research & Trials Volume 4 (2019), Article ID 4:IJCRT-136, 5 pages
https://doi.org/10.15344/2456-8007/2019/136
Expert Opinion
The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions

Renata O. Pereira1 and Samy I. McFarlane2,*

1Department of Internal Medicine - Endocrinology and Metabolism, FOE Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA
2Department of Internal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NYC 11203, USA
Prof. Samy I. McFarlane, Division of Endocrinology, Department of Internal Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York,11203, USA, Tel: 718-270-6707, Fax: 718- 270-4488; E-mail: smcfarlane@downstate.edu
07 September 2019; 12 September 2019; 14 September 2019
Pereira RO, McFarlane SI (2019) The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions. Int J Clin Res Trials 4: 136. doi: https://doi.org/10.15344/2456-8007/2019/136

References

  1. Age-Adjusted Percentage with Overweight or Obesity CDC
  2. Thoonen R, Hindle AG, Scherrer-Crosbie M (2016) Brown adipose tissue: The heat is on the heart. Am J Physiol Heart Circ Physiol 310: 1592-1605 [CrossRef] [Google Scholar] [PubMed]
  3. McFarlane SI, Banerji M, Sowers JR (2001) Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab 86: 713-718 [CrossRef] [Google Scholar] [PubMed]
  4. Karam J, McFarlane S (2010) Tackling obesity: new therapeutic agents for assisted weight loss. Diabetes Metab Syndr Obes 3: 95-112 [Google Scholar] [PubMed]
  5. McFarlane SI, Jacober SJ, Winer N, Kaur J, Castro JP, et al. (2002) Control of cardiovascular risk factors in patients with diabetes and hypertension at urban academic medical centers. Diabetes Care 25: 718-723 [CrossRef] [Google Scholar] [PubMed]
  6. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, et al. (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360: 1518- 1525 [CrossRef] [Google Scholar] [PubMed]
  7. Tseng YH, Cypess AM, Kahn CR (2010) Cellular bioenergetics as a target for obesity therapy. Nat Rev Drug Discov 9: 465-482 [CrossRef] [Google Scholar] [PubMed]
  8. Ruiz JR, Martinez-Tellez B, Sanchez-Delgado G, Osuna-Prieto FJ, Rensen PCN, et al. (2018) Role of Human Brown Fat in Obesity, Metabolism and Cardiovascular Disease: Strategies to Turn Up the Heat. Prog Cardiovasc Dis 61: 232-245 [CrossRef] [Google Scholar] [PubMed]
  9. Chen YC, Cypess AM, Chen YC, Palmer M, Kolodny G, et al. (2013) Measurement of human brown adipose tissue volume and activity using anatomic MR imaging and functional MR imaging. J Nucl Med 54: 1584- 1587 [CrossRef] [Google Scholar] [PubMed]
  10. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P, et al. (2011) Brown adipose tissue in morbidly obese subjects. PLoS One 6: e17247 [CrossRef] [Google Scholar] [PubMed]
  11. Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, et al. (2011) Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring) 19: 13-16 [CrossRef] [Google Scholar] [PubMed]
  12. Muzik O, Mangner TJ, Leonard WR, Kumar A, Janisse J, et al. (2013) 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med 54: 523-531 [CrossRef] [Google Scholar] [PubMed]
  13. Carpentier AC, Blondin DP, Virtanen KA, Richard D, Haman F, et al. (2018) Brown Adipose Tissue Energy Metabolism in Humans. Front Endocrinol (Lausanne) 9: 447 [CrossRef] [Google Scholar] [PubMed]
  14. Tapia P, Fernandez-Galilea M, Robledo F, Mardones P, Galgani JE, et al. (2018) Biology and pathological implications of brown adipose tissue: promises and caveats for the control of obesity and its associated complications. Biol Rev Camb Philos Soc 93: 1145-1164 [CrossRef] [Google Scholar] [PubMed]
  15. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, et al. (2014) Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 19: 302-309 [CrossRef] [Google Scholar] [PubMed]
  16. Yoneshiro T, Saito M (2013) Transient receptor potential activated brown fat thermogenesis as a target of food ingredients for obesity management. Curr Opin Clin Nutr Metab Care 16: 625-631 [CrossRef] [Google Scholar] [PubMed]
  17. Speakman JR, Heidari-Bakavoli S (2016) Type 2 diabetes, but not obesity, prevalence is positively associated with ambient temperature. Sci Rep 6: 30409 [Google Scholar]
  18. Fernandez-Verdejo R, Marlatt KL, Ravussin E, Galgani JE (2019) Contribution of brown adipose tissue to human energy metabolism. Mol Aspects Med [CrossRef] [Google Scholar] [PubMed]
  19. Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, et al. (2011) 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 96: 192-129 [CrossRef] [Google Scholar] [PubMed]
  20. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, et al. (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58: 1526-1531 [CrossRef] [Google Scholar] [PubMed]
  21. Blauw LL, Aziz NA, Tannemaat MR, Blauw CA, de Craen AJ, et al. (2017) Diabetes incidence and glucose intolerance prevalence increase with higher outdoor temperature. BMJ Open Diabetes Res Care 5: e000317 [CrossRef] [Google Scholar]
  22. Matsushita M, Yoneshiro T, Aita S, Kameya T, Sugie H, et al. (2014) Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes (Lond) 38: 812-817 [CrossRef] [Google Scholar] [PubMed]
  23. Chondronikola M, Volpi E, Borsheim E, Porter C, Annamalai P, et al. (2014) Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes. 63: 4089-4099 [CrossRef] [Google Scholar] [PubMed]
  24. Hanssen MJ, Hoeks J, Brans B, van der Lans AA, Schaart G, et al. (2015) Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med 21: 863-865 [CrossRef] [Google Scholar] [PubMed]
  25. Hanssen MJ, van der Lans AA, Brans B, Hoeks J, Jardon KM, et al. (2016) Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans. Diabetes 65: 1179-1189 [CrossRef] [Google Scholar] [PubMed]
  26. Din USU, Brook MS, Selby A, Quinlan J, Boereboom C, et al. (2018) A doubleblind placebo controlled trial into the impacts of HMB supplementation and exercise on free-living muscle protein synthesis, muscle mass and function, in older adults. Clin Nutr [CrossRef] [Google Scholar] [PubMed]
  27. De Lorenzo F, Mukherjee M, Kadziola Z, Sherwood R, Kakkar VV, et al. (1998) Central cooling effects in patients with hypercholesterolaemia. Clin Sci (Lond) 95: 213-217 [Google Scholar] [PubMed]
  28. Ouellet V, Labbe SM, Blondin DP, Phoenix S, Guerin B, et al. (2012) Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest. 2012;122: 545-552 [CrossRef] [Google Scholar] [PubMed]
  29. Baskin AS, Linderman JD, Brychta RJ, McGehee S, Anflick-Chames E, et al. (2018) Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a beta3-Adrenergic Receptor Agonist. Diabetes 67: 2113-2125 [CrossRef] [Google Scholar] [PubMed]
  30. Redman LM, de Jonge L, Fang X, Gamlin B, Recker D, et al. (2007) Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study. J Clin Endocrinol Metab 92: 527-531 [CrossRef] [Google Scholar] [PubMed]
  31. Weyer C, Tataranni PA, Snitker S, Danforth E Jr, Ravussin E, et al. (1998) Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans. Diabetes 47: 1555-1561 [CrossRef] [Google Scholar] [PubMed]
  32. Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, et al. (2015) Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab 21: 33-38 [CrossRef] [Google Scholar] [PubMed]
  33. Gustafson D (2019) Adipose Tissue Complexities in Dyslipidemias [Google Scholar]
  34. Gunawardana SC, Piston DW (2015) Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant. Am J Physiol Endocrinol Metab 308: 1043-1055 [CrossRef] [Google Scholar] [PubMed]
  35. Nicolini G, Pitto L, Kusmic C, Balzan S, Sabatino L, et al. (2013) New insights into mechanisms of cardioprotection mediated by thyroid hormones. J Thyroid Res 2013: 264387 [CrossRef] [Google Scholar] [PubMed]
  36. de Jesus LA, Carvalho SD, Ribeiro MO, Schneider M, Kim SW, et al. (2001) The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest 108: 1379-1385 [CrossRef] [Google Scholar] [PubMed]
  37. Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, et al. (2014) The brown fatenriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med 20: 1436-1443 [CrossRef] [Google Scholar] [PubMed]
  38. Liu SQ, Tefft BJ, Roberts DT, Zhang LQ, Ren Y, et al. (2012) Cardioprotective proteins upregulated in the liver in response to experimental myocardial ischemia. Am J Physiol Heart Circ Physiol 303: 1446-1458 [CrossRef] [Google Scholar] [PubMed]
  39. Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, et al. (2013) Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 123: 215-223 [CrossRef] [Google Scholar] [PubMed]
  40. Pal M, Febbraio MA, Whitham M (2014) From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation. Immunol Cell Biol 92: 331-339 [CrossRef] [Google Scholar] [PubMed]
  41. Fontes JA, Rose NR, Cihakova D (2015) The varying faces of IL-6: From cardiac protection to cardiac failure. Cytokine 74: 62-68 [CrossRef] [Google Scholar] [PubMed]
  42. Gimeno RE, Moller DE (2014) FGF21-based pharmacotherapy--potential utility for metabolic disorders. Trends Endocrinol Metab 25: 303-311 [CrossRef] [Google Scholar] [PubMed]
  43. Planavila A, Redondo I, Hondares E, Vinciguerra M, Munts C, et al. (2013) Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat Commun 4: 2019 [CrossRef] [Google Scholar] [PubMed]
  44. Liu SQ, Roberts D, Kharitonenkov A, Zhang B, Hanson SM, et al. (2013) Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue. Sci Rep 3: 2767 [CrossRef] [Google Scholar] [PubMed]
  45. Nishimura T, Nakatake Y, Konishi M, Itoh N (2000) Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta 1492: 203-206 [CrossRef] [Google Scholar] [PubMed]
  46. Pereira RO, Tadinada SM, Zasadny FM, Oliveira KJ, Pires KMP, et al. (2017) OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance. EMBO J 36: 2126-2145 [CrossRef] [Google Scholar] [PubMed]
  47. Flicker D, Sancak Y, Mick E, Goldberger O, Mootha VK (2019) Exploring the In Vivo Role of the Mitochondrial Calcium Uniporter in Brown Fat Bioenergetics. Cell Rep 27: 1364-1375 [CrossRef] [Google Scholar] [PubMed]
  48. Patel S, Alvarez-Guaita A, Melvin A, Rimmington D, Dattilo A, et al. (2019) GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans. Cell Metab 29: 707-718 [CrossRef] [Google Scholar] [PubMed]
  49. Mullican SE, Lin-Schmidt X, Chin CN, Chavez JA, Furman JL, et al. (2017) GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat Med 23: 1150-1157 [CrossRef] [Google Scholar] [PubMed]
  50. Zhang M, Pan K, Liu Q, Zhou X, Jiang T, et al. (2016) Growth differentiation factor 15 may protect the myocardium from noreflow by inhibiting the inflammatorylike response that predominantly involves neutrophil infiltration. Mol Med Rep 13: 623-632 [CrossRef] [Google Scholar] [PubMed]
  51. Zhang Y, Moszczynski LA, Liu Q, Jiang J, Zhao D, et al. (2017) Overexpression of growth differentiation factor 15 (GDF15) preventing cold ischemia reperfusion (I/R) injury in heart transplantation through Foxo3a signaling. Oncotarget 8: 36531-36544 [CrossRef] [Google Scholar] [PubMed]
  52. Preusch MR, Baeuerle M, Albrecht C, Blessing E, Bischof M, et al. (2013) GDF-15 protects from macrophage accumulation in a mousemodel of advanced atherosclerosis. Eur J Med Res 18: 19 [CrossRef] [Google Scholar] [PubMed]
  53. Luan HH, Wang A, Hilliard BK, Carvalho F, Rosen CE, et al. (2019) GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell 178: 1231-1244 [CrossRef] [Google Scholar] [PubMed]
  54. Wollert KC, Kempf T, Wallentin L (2017) Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease. Clin Chem 63: 140-151 [CrossRef] [Google Scholar] [PubMed]
  55. Lynes MD, Leiria LO, Lundh M, Bartelt A, Shamsi F, et al. (2017) The coldinduced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med 23: 631-637 [CrossRef] [Google Scholar] [PubMed]
  56. Stanford KI, Lynes MD, Takahashi H, Baer LA, Arts PJ, et al. (2018) 12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake. Cell Metab 27: 1111-1120 [CrossRef] [Google Scholar] [PubMed]
  57. Bannehr M, Lohr L, Gelep J, Haverkamp W, Schunck WH, et al. (2019) Linoleic Acid Metabolite DiHOME Decreases Post-ischemic Cardiac Recovery in Murine Hearts. Cardiovasc Toxicol 19: 365-371 [CrossRef] [Google Scholar] [PubMed]
  58. Thoonen R, Ernande L, Cheng J, Nagasaka Y, Yao V, et al. (2015) Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy. J Mol Cell Cardiol 84: 202-211 [CrossRef] [Google Scholar] [PubMed]