Obezite Yönetiminde Adipoz Doku Kahverengileşmesi
Yıl 2023,
Cilt: 7 Sayı: 1, 81 - 91, 28.04.2023
Hümeyra Başkent
,
Nazlı Nur Aslan Çin
,
Taner Bayraktaroğlu
,
Figen Barut
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
Kaynakça
- 1. Yıldırım M, Akyol A, Ersoy G. Şişmanlik (Obezite) Ve Fiziksel
Aktivite, 2008.
- 2. Catenacci VA, Hill JO, Wyatt HR. The obesity epidemic. Clin
Chest Med. 2009;30(3):415-444, vii.
- 3. Cannon B, Nedergaard J. Brown adipose tissue: Function and
physiological significance. Physiol Rev. 2004;84(1):277-359.
- 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. 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. 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. 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. Schulz TJ, Tseng YH. Brown adipose tissue: Development,
metabolism and beyond. Biochem J. 2013;453(2):167-78.
- 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.
- 11. Mermer M, Nilüfer A. Adipoz doku ve enerji metabolizması
üzerine etkileri. Süleyman Demirel Üniversitesi Sağlık
Bilimleri Dergisi. 2017;8(3): 40-46.
- 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.
- 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.
- 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.
- 15. Bartelt A, Heeren J. Adipose tissue browning and metabolic
health. Nat Rev Endocrinol. 2014;10(1):24-36.
- 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.
- 17. Palou A, Picó C, Bonet ML, Oliver P. The uncoupling protein,
thermogenin. Int J Biochem Cell Biol. 1998;30(1):7-11.
- 18. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling
and obesity. J Clin Invest. 2011;121(6):2094-2101.
- 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.
- 20. Wijers SL, Saris WH, van Marken Lichtenbelt WD. Coldinduced
adaptive thermogenesis in lean and obese. Obesity
(Silver Spring). 2010;18(6):1092-1099.
- 21. Kiefer FW. Browning and thermogenic programing of adipose
tissue. Best Pract Res Clin Endocrinol Metab. 2016;30(4):479-
485.
- 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.
- 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.
- 24. Farmer SR. Transcriptional control of adipocyte formation.
Cell Metab. 2006;4(4):263-273.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 33. Aldiss P, Betts J, Sale C, Pope M, Budge H, Symonds ME.
Exercise-induced ‘browning’ of adipose tissues. Metabolism.
2018;81:63-70.
- 34. Crujeiras AB, Pardo M, Casanueva FF. Irisin: ‘fat’ or artefact.
Clin Endocrinol (Oxf). 2015;82(4):467-474.
- 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.
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Klinikleri J Endocrin. 2016;11(1):15-21.
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Adipose Tissue Browning in Obesity Management
Yıl 2023,
Cilt: 7 Sayı: 1, 81 - 91, 28.04.2023
Hümeyra Başkent
,
Nazlı Nur Aslan Çin
,
Taner Bayraktaroğlu
,
Figen Barut
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
Kaynakça
- 1. Yıldırım M, Akyol A, Ersoy G. Şişmanlik (Obezite) Ve Fiziksel
Aktivite, 2008.
- 2. Catenacci VA, Hill JO, Wyatt HR. The obesity epidemic. Clin
Chest Med. 2009;30(3):415-444, vii.
- 3. Cannon B, Nedergaard J. Brown adipose tissue: Function and
physiological significance. Physiol Rev. 2004;84(1):277-359.
- 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. 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. 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. 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. Schulz TJ, Tseng YH. Brown adipose tissue: Development,
metabolism and beyond. Biochem J. 2013;453(2):167-78.
- 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.
- 11. Mermer M, Nilüfer A. Adipoz doku ve enerji metabolizması
üzerine etkileri. Süleyman Demirel Üniversitesi Sağlık
Bilimleri Dergisi. 2017;8(3): 40-46.
- 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.
- 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.
- 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.
- 15. Bartelt A, Heeren J. Adipose tissue browning and metabolic
health. Nat Rev Endocrinol. 2014;10(1):24-36.
- 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.
- 17. Palou A, Picó C, Bonet ML, Oliver P. The uncoupling protein,
thermogenin. Int J Biochem Cell Biol. 1998;30(1):7-11.
- 18. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling
and obesity. J Clin Invest. 2011;121(6):2094-2101.
- 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.
- 20. Wijers SL, Saris WH, van Marken Lichtenbelt WD. Coldinduced
adaptive thermogenesis in lean and obese. Obesity
(Silver Spring). 2010;18(6):1092-1099.
- 21. Kiefer FW. Browning and thermogenic programing of adipose
tissue. Best Pract Res Clin Endocrinol Metab. 2016;30(4):479-
485.
- 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.
- 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.
- 24. Farmer SR. Transcriptional control of adipocyte formation.
Cell Metab. 2006;4(4):263-273.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 33. Aldiss P, Betts J, Sale C, Pope M, Budge H, Symonds ME.
Exercise-induced ‘browning’ of adipose tissues. Metabolism.
2018;81:63-70.
- 34. Crujeiras AB, Pardo M, Casanueva FF. Irisin: ‘fat’ or artefact.
Clin Endocrinol (Oxf). 2015;82(4):467-474.
- 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.
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