Divisions of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany.
Mol Metab. 2017 Mar 28;6(6):482-493. doi: 10.1016/j.molmet.2017.03.004. eCollection 2017 Jun.
Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology.
We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels. Vaspin expression was analyzed in isolated white and brown adipocytes during adipogenesis and in response to adrenergic stimuli. DNA-methylation within the vaspin promoter was analyzed to investigate acute epigenetic changes after cold-exposure in BAT.
Our results demonstrate a strong induction of vaspin mRNA and protein expression specifically in BAT of both cold-exposed and high-fat (HF) or high-sugar (HS) fed mice. While obesogenic diets also upregulated hepatic mRNA levels, cold exposure tended to increase gene expression of inguinal white adipose tissue (iWAT) depots. Concomitantly, vaspin plasma levels were decreased upon obesogenic or thermogenic triggers. Vaspin expression was increased during adipogenesis but unaffected by sympathetic activation in brown adipocytes. Analysis of vaspin promoter methylation in AT revealed lowest methylation levels in BAT, which were acutely reduced after cold exposure.
Our data demonstrate a novel BAT-specific regulation of gene expression upon physiological stimuli with acute epigenetic changes that may contribute to cold-induced expression in BAT. We conclude that these findings indicate functional relevance and potentially beneficial effects of vaspin in BAT function.
多项研究表明内脏脂肪组织来源的丝氨酸蛋白酶抑制剂(vaspin)具有抗糖尿病和抗肥胖作用,因此激发了其在治疗肥胖相关疾病中的潜在用途。本研究旨在揭示 vaspin 表达和分泌的生理调节因子,特别关注其在棕色脂肪组织(BAT)生物学中的作用。
我们分析了肥胖饮食和冷暴露对肝脏和白色及棕色脂肪组织(AT)中 vaspin 表达和血浆水平的影响。在脂肪生成过程中以及对肾上腺素能刺激的反应中,分析了分离的白色和棕色脂肪细胞中 vaspin 的表达。分析 vaspin 启动子内的 DNA 甲基化,以研究冷暴露后 BAT 中的急性表观遗传变化。
我们的结果表明,冷暴露和高脂肪(HF)或高糖(HS)喂养的小鼠的 BAT 中,vaspin mRNA 和蛋白表达均得到强烈诱导。虽然肥胖饮食也上调了肝脏 mRNA 水平,但冷暴露往往会增加腹股沟白色脂肪组织(iWAT)的基因表达。同时,肥胖或产热触发会降低 vaspin 的血浆水平。vaspin 在脂肪生成过程中表达增加,但在棕色脂肪细胞中不受交感神经激活的影响。AT 中 vaspin 启动子甲基化分析显示,BAT 中的甲基化水平最低,冷暴露后急性降低。
我们的数据表明,生理刺激下 BAT 中存在新型的基因表达特异性调节,伴有急性表观遗传变化,这可能有助于 BAT 中冷诱导的表达。我们得出结论,这些发现表明 vaspin 在 BAT 功能中具有功能相关性和潜在的有益作用。