Brown adipose tissue (BAT) specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation

Abstract

ObjectiveSeveral 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.MethodsWe 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.ResultsOur 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 vaspin mRNA levels, cold exposure tended to increase vaspin 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.ConclusionsOur data demonstrate a novel BAT-specific regulation of vaspin gene expression upon physiological stimuli in vivo 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.

Insulin induces expression of the hepatic <i>vaspin</i> gene

“…The expression pattern of mouse vaspin mRNA was more similar to that of human vaspin mRNA [4,5]. Furthermore, our result supports the earlier result for mouse vaspin [6]. We have demonstrated that the expression of hepatic vaspin was markedly decreased in liverspecific C/EBPα knockout mice.…”

“…In addition, vaspin mRNA level was higher in OLETF rats than in non-diabetic control rats [1]. Further, vaspin expression was observed in humans [4,5] or mice [6] in several tissues such as adipose tissue, liver, skeletal muscle, pancreas, and skin, with the highest production being observed in the liver or skin.…”

Does a high-fat diet-induced obesity model brown adipose tissue thermogenesis? A systematic review

“…Seven studies [8][9][10][11][12][13][14] were selected after all the eligibility criteria were met (Table I). Regarding the location in which the studies were carried out, two were from Japan, and the others were from Spain, the United States of America, Sweden, Germany, and Canada.…”

The role of DNA methylation in thermogenic adipose biology

“…Another study suggests that DNA methylation is involved in the brown adipocyte-specific expression of Vaspin (visceral adipose tissue-derived serine protease inhibitor; SERPINA12). Vaspin is an adipokine suggested to be anti-diabetic and antiobesogenic [48] because it inhibits hepatic gluconeogenesis and improves insulin signal transduction [49][50][51]. A microarray study found that Vaspin level is strongly upregulated in BAT after cold exposure, and another study found that Vaspin promoter regions in BAT are more hypomethylated than white adipose depots in mice fed with normal chow.…”