棕色脂肪形成的内分泌及环境影响因素研究(3)
3.3高原環境 地理学上,海拔在500米以上称为高原,而在医学上,在诊断各类高原疾病时,我们确定了2500米以上为高原。世界高原分布广,面积大,人口多,且亚洲分布高原较多,青藏高原是世界海拔最高的高原,平均海拔4000米以上。高原地区大气中的氧含量和氧分压随海拔增高而递减,气温也随海拔高度的升高而降低。因此,寒冷和缺氧是高原生活的重大挑战。以往研究表明,高原鼠兔已经进化出了适应机制来应对这些挑战,比如高静息代谢率(RMR)和非颤抖的热生成(NST),以及较低的氧气消耗来应对缺氧[27]。通过间歇性冷接触研究啮齿动物的冷适应,我们发现在温暖的温度下,鼠兔几乎没有经典的BAT,但是在寒冷暴露下,白色脂肪组织棕色化会迅速被观察到[28]。低氧通气反应是机体对抗缺氧环境的反射性防御反应,白振忠等的研究发现[29],高原鼠兔的低氧通气反应在表现形式上是稳定且不易受到低氧环境的刺激从而发生急剧的变化,这一特征是高原鼠兔低氧适应的重要分子机制。
4总结
肥胖与心血管疾病、2型糖尿病和某些癌症等均相关,肥胖带来的健康问题已经超乎人类想象,与超重和肥胖有关的死亡,超过2/3的是由心血管疾病(CVD)引起的。现在人们认识到,成年人类中也存在着大量活跃的棕色脂肪库,参与机体能量平衡和脂肪调节,我们可以认为拥有更多BAT的人能够更好地燃烧多余的热量,由此看来,BAT可以成为治疗肥胖的靶器官,这需要未来更多的研究进一步支持。当然,到现在为止,白色脂肪棕色化的作用机制也尚未完全阐明,仍需我们进一步探究。探讨白色脂肪棕色化的内分泌调节及其环境影响因素,深入地了解BAT的潜在能力,将使我们能够更好地控制这些细胞,以改善系统能量代谢和葡萄糖稳态,为对抗人类肥胖和相关代谢紊乱提供新的治疗策略。
, 百拇医药
参考文献:
[1]Gill JA,La Merrill MA.An emerging role for epigenetic regulation of Pgc-1α expression in environmentally stimulated brown adipose thermogenesis[J].Environmental Epigenetics,2017,3(2):dvx009.
[2]Lin JZ,Farmer SR.Morphogenetics in brown,beige and white fat development[J].Adipocyte,2016,5(2):130-135.
[3]Cypess AM,Lehman S,Williams G,et al.Identification and importance of brown adipose tissue in adult humans[J].N Engl J Med,2009,360(15):1509-1517.
, 百拇医药
[4]Betz MJ,Enerback S.Human brown adipose tissue:shat we have learned so far[J].Diabetes,2015,64(7):2352-2360.
[5]Cannon B,Nedergaard J.Brown adipose tissue:functionand physiological significance[J].Physiol Rev,2004(84):277-359.
[6]Cypess AM,White AP,Vernochet C,et al.Anatomical localization,gene expression profiling and functional characterization of adult human neck brown fat[J].Nat Med,2013,19(5):635-639.
, http://www.100md.com
[7]Sanchis-Gomar F,Perez-Quilis C.The p38-PGC-1α-irisinbetatrophin axis:exploring new pathways in insulin resistance[J].Adipocyte,2014(3):67-68.
[8]Kurdiova T,Balaz M,Vician M,et al.Effects of obesity,diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue:In vivo and in vitro studies[J].Physioy,2014(592):1091-1107.
[9]Contreras GA,Lee YH,Mottillo EP,et al.Inducible rrown adipocytes in subcutaneous inguinal white fat:the role of continuous sympathetic stimulation[J].Am J Physiol Endocrinol Metab,2014,307(9):E793-E799.
, http://www.100md.com
[10]Than A,Xu S,Li R,et al.Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis[J].Signal Transduction and Targeted Therapy,2017(2):17022.
[11]Fisher FM,Kleiner S,Douris N,et al.FGF21 regulates PGC-1alpha and browning of whiteadipose tissues in adaptive thermogenesis[J].Genes Dev,2012,26(3):271-281., http://www.100md.com(庄俐 张惠莉 张瑞霞)
4总结
肥胖与心血管疾病、2型糖尿病和某些癌症等均相关,肥胖带来的健康问题已经超乎人类想象,与超重和肥胖有关的死亡,超过2/3的是由心血管疾病(CVD)引起的。现在人们认识到,成年人类中也存在着大量活跃的棕色脂肪库,参与机体能量平衡和脂肪调节,我们可以认为拥有更多BAT的人能够更好地燃烧多余的热量,由此看来,BAT可以成为治疗肥胖的靶器官,这需要未来更多的研究进一步支持。当然,到现在为止,白色脂肪棕色化的作用机制也尚未完全阐明,仍需我们进一步探究。探讨白色脂肪棕色化的内分泌调节及其环境影响因素,深入地了解BAT的潜在能力,将使我们能够更好地控制这些细胞,以改善系统能量代谢和葡萄糖稳态,为对抗人类肥胖和相关代谢紊乱提供新的治疗策略。
, 百拇医药
参考文献:
[1]Gill JA,La Merrill MA.An emerging role for epigenetic regulation of Pgc-1α expression in environmentally stimulated brown adipose thermogenesis[J].Environmental Epigenetics,2017,3(2):dvx009.
[2]Lin JZ,Farmer SR.Morphogenetics in brown,beige and white fat development[J].Adipocyte,2016,5(2):130-135.
[3]Cypess AM,Lehman S,Williams G,et al.Identification and importance of brown adipose tissue in adult humans[J].N Engl J Med,2009,360(15):1509-1517.
, 百拇医药
[4]Betz MJ,Enerback S.Human brown adipose tissue:shat we have learned so far[J].Diabetes,2015,64(7):2352-2360.
[5]Cannon B,Nedergaard J.Brown adipose tissue:functionand physiological significance[J].Physiol Rev,2004(84):277-359.
[6]Cypess AM,White AP,Vernochet C,et al.Anatomical localization,gene expression profiling and functional characterization of adult human neck brown fat[J].Nat Med,2013,19(5):635-639.
, http://www.100md.com
[7]Sanchis-Gomar F,Perez-Quilis C.The p38-PGC-1α-irisinbetatrophin axis:exploring new pathways in insulin resistance[J].Adipocyte,2014(3):67-68.
[8]Kurdiova T,Balaz M,Vician M,et al.Effects of obesity,diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue:In vivo and in vitro studies[J].Physioy,2014(592):1091-1107.
[9]Contreras GA,Lee YH,Mottillo EP,et al.Inducible rrown adipocytes in subcutaneous inguinal white fat:the role of continuous sympathetic stimulation[J].Am J Physiol Endocrinol Metab,2014,307(9):E793-E799.
, http://www.100md.com
[10]Than A,Xu S,Li R,et al.Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis[J].Signal Transduction and Targeted Therapy,2017(2):17022.
[11]Fisher FM,Kleiner S,Douris N,et al.FGF21 regulates PGC-1alpha and browning of whiteadipose tissues in adaptive thermogenesis[J].Genes Dev,2012,26(3):271-281., http://www.100md.com(庄俐 张惠莉 张瑞霞)