Obezite Yönetiminde Adipoz Doku Kahverengileşmesi

Öz

Tüm dünya sorunu olan obezitenin tedavisinde güncel olarak terapötik stratejiler geliştirilmektedir. Memelilerde, işlevleri ve morfolojileri bakımından farklılık gösteren farklı iki tip adipoz doku mevcuttur. Bunlar, embriyogenez sırasında ortaya çıkan kahverengi adipoz doku (KAD); ve doğum sonrası gelişen beyaz adipoz dokudur (BAD). KAD’nun hacmi, enerji harcaması ile pozitif ilişkili olduğu ve obez kişilerde zayıf bireylere göre önemli ölçüde düşük olduğu bilinmektedir. KAD indüksiyonunu ve/veya aktivasyonunu hedefleyen stratejiler, obezite tedavisinde potansiyel olarak faydalı olabileceği düşünülmektedir. Son yıllarda yapılan araştırmalar, KAD aktivasyonu ve BAD kahverengileşmesi ile ilgili mekanizmalar üzerine olan ilgiyi önemli ölçüde artırmaktadır. Bu mekanizmaları amaçlayan kimyasal bileşiklerin yanı sıra çeşitli farmakolojik olmayan bazı müdahale yaklaşımları bulunmaktadır. Bu derlemede, KAD aktivasyonu ve BAD kahverengileşmesi sürecindeki potansiyel terapötik hedefler ve bunları amaçlayan mevcut stratejilere ilişkin kavramlar özetlenmiştir

Anahtar Kelimeler

• Kahverengi adipoz doku
• beyaz adipoz doku
• adipoz doku kahverengileşmesi
• termogenez
• obezite

Adipose Tissue Browning in Obesity Management

Öz

Recently, therapeutic strategies have been developed for the treatment of obesity, which is a worldwide problem. There are two different types of adipose tissue in mammals that differ in their function and morphology. These are brown adipose tissue (BAT), which develops during embryogenesis and white adipose tissue (WAT), which develops after postnatal. It is known that the volume of BAT is positively associated with energy discharge and is significantly lower in obese individuals than in slim individuals. Strategies targeting the BAT induction and/or activation are considered potentially useful in the treatment of obesity. Recent research initiatives have significantly attracted the interest in the mechanisms associated with the BAT activation and WAT browning. In addition to the chemical compounds focusing on these mechanisms, there are various non-pharmacological intervention approaches. In this review, potential therapeutic targets in BAT activation and WAT browning process as well as the concepts related to the strategies targeting them are summarized

Anahtar Kelimeler

• Brown adipose tissue
• white adipose tissue
• adipose tissue browning
• thermogenesis
• obesity

Kaynakça

1. 1. Yıldırım M, Akyol A, Ersoy G. Şişmanlik (Obezite) Ve Fiziksel Aktivite, 2008.
2. 2. Catenacci VA, Hill JO, Wyatt HR. The obesity epidemic. Clin Chest Med. 2009;30(3):415-444, vii.
3. 3. Cannon B, Nedergaard J. Brown adipose tissue: Function and physiological significance. Physiol Rev. 2004;84(1):277-359.
4. 4. Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol (Lausanne). 2016;7:30.
5. 5. Contreras C, Nogueiras R, Diéguez C, Medina-Gómez G, López M. Hypothalamus and thermogenesis: Heating the BAT, browning the WAT. Mol Cell Endocrinol. 2016;438:107-115.
6. 6. Kuryłowicz A, Puzianowska-Kuźnicka M. Induction of Adipose Tissue Browning as a Strategy to Combat Obesity. Int J Mol Sci. 2020;21(17):6241.
7. 7. Concha F, Prado G, Quezada J, Ramirez A, Bravo N, Flores C, Herrera JJ, Lopez N, Uribe D, Duarte-Silva L, Lopez-Legarrea P, Garcia-Diaz DF. Nutritional and non-nutritional agents that stimulate white adipose tissue browning. Rev Endocr Metab Disord. 2019;20(2):161-171.
8. 8. Schulz TJ, Tseng YH. Brown adipose tissue: Development, metabolism and beyond. Biochem J. 2013;453(2):167-78.

9. 9. Saely CH, Geiger K, Drexel H. Brown versus white adipose tissue: A mini-review. Gerontology. 2012;58(1):15-23. 10. Medina-Gómez G. Mitochondria and endocrine function of adipose tissue. Best Pract Res Clin Endocrinol Metab. 2012;26(6):791-804.
10. 11. Mermer M, Nilüfer A. Adipoz doku ve enerji metabolizması üzerine etkileri. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2017;8(3): 40-46.
11. 12. Cheng L, Wang J, Dai H, Duan Y, An Y, Shi L, Lv Y, Li H, Wang C, Ma Q, Li Y, Li P, Du H, Zhao B. Brown and beige adipose tissue: A novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte. 2021;10(1):48-65.
12. 13. Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, Nedergaard J, Cannon B. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci U S A. 2007;104(11):4401-4406.
13. 14. Jiménez G, López-Ruiz E, Griñán-Lisón C, Antich C, Marchal JA. Brown adipose tissue and obesity. Obesity: A Practical Guide, 2016:13-28.
14. 15. Bartelt A, Heeren J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol. 2014;10(1):24-36.
15. 16. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293(2):E444-452.
16. 17. Palou A, Picó C, Bonet ML, Oliver P. The uncoupling protein, thermogenin. Int J Biochem Cell Biol. 1998;30(1):7-11.
17. 18. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121(6):2094-2101.
18. 19. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509- 1517.
19. 20. Wijers SL, Saris WH, van Marken Lichtenbelt WD. Coldinduced adaptive thermogenesis in lean and obese. Obesity (Silver Spring). 2010;18(6):1092-1099.
20. 21. Kiefer FW. Browning and thermogenic programing of adipose tissue. Best Pract Res Clin Endocrinol Metab. 2016;30(4):479- 485.
21. 22. Altuntuzcu Ş. 18-FDG PET/CT ile belirlenen kahverengi yağ dokusu glukoz uptake’i ile açlık kan glukozunun ilişkisi. Turk Diab Obes. 2019;3(3): 145-148.
22. 23. Xue R, Lynes MD, Dreyfuss JM, Shamsi F, Schulz TJ, Zhang H, Huang TL, Townsend KL, Li Y, Takahashi H, Weiner LS, White AP, Lynes MS, Rubin LL, Goodyear LJ, Cypess AM, Tseng YH. Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes. Nat Med. 2015;21(7):760-768.
23. 24. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab. 2006;4(4):263-273.
24. 25. Montanari T, Pošćić N, Colitti M. Factors involved in whiteto- brown adipose tissue conversion and in thermogenesis: A review. Obes Rev. 2017;18(5):495-513.
25. 26. Crichton PG, Lee Y, Kunji ER. The molecular features of uncoupling protein 1 support a conventional mitochondrial carrier-like mechanism. Biochimie. 2017;134:35-50.
26. 27. Rosell M, Kaforou M, Frontini A, Okolo A, Chan YW, Nikolopoulou E, Millership S, Fenech ME, MacIntyre D, Turner JO, Moore JD, Blackburn E, Gullick WJ, Cinti S, Montana G, Parker MG, Christian M. Brown and white adipose tissues: Intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol Endocrinol Metab. 2014;306(8):E945-964.
27. 28. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92(6):829-839.
28. 29. Kern PA, Finlin BS, Zhu B, Rasouli N, McGehee RE Jr, Westgate PM, Dupont-Versteegden EE. The effects of temperature and seasons on subcutaneous white adipose tissue in humans: Evidence for thermogenic gene induction. J Clin Endocrinol Metab. 2014;99(12):E2772-2779.
29. 30. Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, Miyagawa M, Tsujisaki M, Saito M. Agerelated decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring). 2011;19(9):1755-1760.
30. 31. Shimizu Y, Nikami H, Saito M. Sympathetic activation of glucose utilization in brown adipose tissue in rats. J Biochem. 1991;110(5):688-692.
31. 32. Murano I, Barbatelli G, Giordano A, Cinti S. Noradrenergic parenchymal nerve fiber branching after cold acclimatisation correlates with brown adipocyte density in mouse adipose organ. J Anat. 2009;214(1):171-178.
32. 33. Aldiss P, Betts J, Sale C, Pope M, Budge H, Symonds ME. Exercise-induced ‘browning’ of adipose tissues. Metabolism. 2018;81:63-70.
33. 34. Crujeiras AB, Pardo M, Casanueva FF. Irisin: ‘fat’ or artefact. Clin Endocrinol (Oxf). 2015;82(4):467-474.
34. 35. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-468.
35. 36. Aslıhan İ, Ünübol Aypak S. İrisin ve metabolik etkileri. Turkiye Klinikleri J Endocrin. 2016;11(1):15-21.
36. 37. Aslan NN, Yardımcı H. Obezite üzerine etkili yeni bir hormon: İrisin. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2017;6(3):176-183.
37. 38. Yoneshiro T, Matsushita M, Saito M. Translational aspects of brown fat activation by food-derived stimulants, in Brown Adipose Tissue, Springer, 2018:359-379.
38. 39. Baskaran P, Krishnan V, Ren J, Thyagarajan B. Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms. Br J Pharmacol. 2016;173(15):2369-2389.
39. 40. Ohyama K, Nogusa Y, Shinoda K, Suzuki K, Bannai M, Kajimura S. A synergistic antiobesity effect by a combination of capsinoids and cold temperature through promoting beige adipocyte biogenesis. Diabetes. 2016;65(5):1410-1423.
40. 41. Andrade JM, Frade AC, Guimarães JB, Freitas KM, Lopes MT, Guimarães AL, de Paula AM, Coimbra CC, Santos SH. Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. Eur J Nutr. 2014;53(7):1503-1510.
41. 42. Alberdi G, Rodríguez VM, Miranda J, Macarulla MT, Churruca I, Portillo MP. Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats. Food Chem. 2013;141(2):1530-1535.
42. 43. Wang S, Liang X, Yang Q, Fu X, Rogers CJ, Zhu M, Rodgers BD, Jiang Q, Dodson MV, Du M. Resveratrol induces brownlike adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1. Int J Obes (Lond). 2015;39(6):967-976.
43. 44. Lone J, Choi JH, Kim SW, Yun JW. Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. J Nutr Biochem. 2016;27:193-202.
44. 45. Nomura S, Ichinose T, Jinde M, Kawashima Y, Tachiyashiki K, Imaizumi K. Tea catechins enhance the mRNA expression of uncoupling protein 1 in rat brown adipose tissue. J Nutr Biochem. 2008;19(12):840-847.
45. 46. Nirengi S, Amagasa S, Homma T, Yoneshiro T, Matsumiya S, Kurosawa Y, Sakane N, Ebi K, Saito M, Hamaoka T. Daily ingestion of catechin-rich beverage increases brown adipose tissue density and decreases extramyocellular lipids in healthy young women. Springerplus. 2016;5(1):1363.
46. 47. Zhao M, Chen X. Eicosapentaenoic acid promotes thermogenic and fatty acid storage capacity in mouse subcutaneous adipocytes. Biochem Biophys Res Commun. 2014;450(4):1446- 1451.
47. 48. Laiglesia LM, Lorente-Cebrián S, Prieto-Hontoria PL, Fernández-Galilea M, Ribeiro SM, Sáinz N, Martínez JA, Moreno-Aliaga MJ. Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects. J Nutr Biochem. 2016;37:76-82.
48. 49. Kim M, Goto T, Yu R, Uchida K, Tominaga M, Kano Y, Takahashi N, Kawada T. Fish oil intake induces UCP1 upregulation in brown and white adipose tissue via the sympathetic nervous system. Sci Rep. 2015;5:18013.
49. 50. You Y, Yuan X, Lee HJ, Huang W, Jin W, Zhan J. Mulberry and mulberry wine extract increase the number of mitochondria during brown adipogenesis. Food Funct. 2015;6(2):401-408.
50. 51. Pajuelo D, Quesada H, Díaz S, Fernández-Iglesias A, Arola- Arnal A, Bladé C, Salvadó J, Arola L. Chronic dietary supplementation of proanthocyanidins corrects the mitochondrial dysfunction of brown adipose tissue caused by diet-induced obesity in Wistar rats. Br J Nutr. 2012;107(2):170- 178.
51. 52. Thiele R, Mueller-Seitz E, Petz M. Chili pepper fruits: presumed precursors of fatty acids characteristic for capsaicinoids. J Agric Food Chem. 2008;56(11):4219-4224.
52. 53. Kawada T, Watanabe T, Takaishi T, Tanaka T, Iwai K. Capsaicininduced beta-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. Proc Soc Exp Biol Med. 1986;183(2):250-256.
53. 54. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature. 1997;389(6653):816-824.
54. 55. Ludy MJ, Moore GE, Mattes RD. The effects of capsaicin and capsiate on energy balance: Critical review and meta-analyses of studies in humans. Chem Senses. 2012;37(2):103-121.
55. 56. Burns J, Yokota T, Ashihara H, Lean ME, Crozier A. Plant foods and herbal sources of resveratrol. J Agric Food Chem. 2002;50(11):3337-3340.
56. 57. Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH. AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes. 2010;59(3):554-563.
57. 58. Hui S, Liu Y, Huang L, Zheng L, Zhou M, Lang H, Wang X, Yi L, Mi M. Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling. Int J Obes (Lond). 2020;44(8):1678-1690.
58. 59. Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, Lu H, Fantus IG, Jin T. Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS One. 2012;7(1):e28784.
59. 60. Di Pierro F, Bressan A, Ranaldi D, Rapacioli G, Giacomelli L, Bertuccioli A. Potential role of bioavailable curcumin in weight loss and omental adipose tissue decrease: preliminary data of a randomized, controlled trial in overweight people with metabolic syndrome. Preliminary study. Eur Rev Med Pharmacol Sci. 2015;19(21):4195-4202.
60. 61. Westerterp-Plantenga M, Diepvens K, Joosen AM, Bérubé- Parent S, Tremblay A. Metabolic effects of spices, teas, and caffeine. Physiol Behav. 2006;89(1):85-91.
61. 62. Rains TM, Agarwal S, Maki KC. Antiobesity effects of green tea catechins: A mechanistic review. J Nutr Biochem. 2011;22(1):1- 7.
62. 63. Basu A, Lucas EA. Mechanisms and effects of green tea on cardiovascular health. Nutr Rev. 2007;65(8 Pt 1):361-375.
63. 64. Anderson BM, Ma DW. Are all n-3 polyunsaturated fatty acids created equal? Lipids Health Dis. 2009;8:33.
64. 65. Lorente-Cebrián S, Costa AG, Navas-Carretero S, Zabala M, Martínez JA, Moreno-Aliaga MJ. Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: A review of the evidence. J Physiol Biochem. 2013;69(3):633-651.
65. 66. Kim J, Okla M, Erickson A, Carr T, Natarajan SK, Chung S. Eicosapentaenoic acid potentiates brown thermogenesis through FFAR4-dependent up-regulation of miR-30b and miR-378. J Biol Chem. 2016;291(39):20551-20562.
66. 67. Anhê FF, Roy D, Pilon G, Dudonné S, Matamoros S, Varin TV, Garofalo C, Moine Q, Desjardins Y, Levy E, Marette A. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015;64(6):872-883.