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慢性冷暴露导致青海高原田鼠(Ochotona curzoniae)皮下脂肪组织褐变和整体代谢改变。

Chronic cold exposure results in subcutaneous adipose tissue browning and altered global metabolism in Qinghai-Tibetan plateau pika (Ochotona curzoniae).

机构信息

Research Center for High Altitude Medicine, Qinghai University Medical College, 810001 Qinghai, Xining, PR China; Key Laboratory for Application of High Altitude Medicine in Qinghai Province, Qinghai University Medical College, 810001 Qinghai, Xining, PR China; Qinghai-Utah Joint Research Key Lab for High Altitude Medicine, Qinghai University Medical College, 810001 Qinghai, Xining, PR China.

Research Center for High Altitude Medicine, Qinghai University Medical College, 810001 Qinghai, Xining, PR China; Key Laboratory for Application of High Altitude Medicine in Qinghai Province, Qinghai University Medical College, 810001 Qinghai, Xining, PR China; Qinghai-Utah Joint Research Key Lab for High Altitude Medicine, Qinghai University Medical College, 810001 Qinghai, Xining, PR China.

出版信息

Biochem Biophys Res Commun. 2018 Jun 2;500(2):117-123. doi: 10.1016/j.bbrc.2018.03.147. Epub 2018 Apr 13.

DOI:10.1016/j.bbrc.2018.03.147
PMID:29626477
Abstract

The plateau pika (Ochotona curzoniae), one of the indigenous animals of the Qinghai-Tibet Plateau, is adapted to life in a cold and hypoxic environment. We conducted a series of genomic, proteomic and morphological studies to investigate whether changes in energy metabolism contribute to adaptation of the plateau pika to cold stress by analyzing summer and winter cohorts. The winter group showed strong morphological and histological features of brown adipose tissue (BAT) in subcutaneous white adipose tissue (sWAT). To obtain molecular evidence of browning of sWAT, we performed reverse transcription and quantitative real-time PCR, which revealed that BAT-specific genes, including uncoupling protein 1 (UCP-1) and PPAR-γ coactivator 1α (PGC-1α), were highly expressed in sWAT from the winter group. Compared with the summer group, Western blot analysis also confirmed that UCP-1, PGC-1α and Cox4 protein levels were significantly increased in sWAT from the winter group. Increased BAT mass in the inter-scapular region of the winter group was also observed. These results suggest that the plateau pika adapts to cold by browning sWAT and increasing BAT in order to increase thermogenesis. These changes are distinct from the previously reported adaptation of highland deer mice. Understanding the regulatory mechanisms underlying this adaptation may lead to novel therapeutic strategies for treating obesity and metabolic disorders.

摘要

高原鼠兔(Ochotona curzoniae)是青藏高原特有的动物之一,适应了高寒缺氧的环境。我们通过对夏季和冬季两个组群进行一系列的基因组、蛋白质组和形态学研究,以探究能量代谢的变化是否有助于高原鼠兔适应寒冷应激。冬季组群在皮下白色脂肪组织(sWAT)中表现出强烈的棕色脂肪组织(BAT)形态和组织学特征。为了获得 sWAT 褐变的分子证据,我们进行了反转录和定量实时 PCR,结果表明 BAT 特异性基因,包括解偶联蛋白 1(UCP-1)和过氧化物酶体增殖物激活受体-γ共激活因子 1α(PGC-1α),在冬季组群的 sWAT 中高度表达。与夏季组群相比,Western blot 分析还证实,冬季组群的 sWAT 中 UCP-1、PGC-1α 和 Cox4 蛋白水平显著增加。冬季组群肩胛间区的 BAT 质量也增加。这些结果表明,高原鼠兔通过 sWAT 的褐变和 BAT 的增加来适应寒冷,以增加产热。这些变化与先前报道的高原鹿鼠的适应不同。了解这种适应的调节机制可能为治疗肥胖症和代谢紊乱提供新的治疗策略。

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