ALK7 expression is specific for adipose tissue, reduced in obesity and correlates to factors implicated in metabolic disease

Abstract

Human adipose tissue is a major site of expression of inhibin beta B (INHBB) which homodimerizes to form the novel adipokine activin B. Our aim was to determine if molecules needed for a local action of activin B are expressed in adipose tissue. Microarray analysis showed that adipose tissue expressed activin type I and II receptors and that the expression of activin receptor-like kinase 7 (ALK7) was adipose tissue specific. In obesity discordant siblings from the SOS Sib Pair study, adipose tissue ALK7 expression was higher in lean (n=90) compared to obese (n=90) subjects (p=4 x 10(-31)). Adipose tissue ALK7 expression correlated with several measures of body fat, carbohydrate metabolism and lipids. In addition, ALK7 and INHBB expression correlated but only in lean subjects and in subjects with normal glucose tolerance. We conclude that activin B may have local effects in adipose tissue and thereby influence obesity and its comorbidities.

Fig. 1

Expression of activin subunits and activin receptors in human adipose tissue analyzed by microarray (A) and ALK7 expression analyzed by real-time PCR (B). (A) For each gene, the expression in subcutaneous (scAT) and omental adipose tissue (omAT) relative to the mean expression level in 65 reference tissues (dashed line) is shown. (B) ALK7 gene expression in human adipose tissue (mean ± SEM, n = 3) and adipocytes (mean ± SEM, n = 3) compared with other human tissues.

Fig. 2

ALK7 (left) and INHBB (right) expression in lean (n = 90) and obese (n = 90) siblings from the SOS Sib Pair study measured by DNA microarray.

Fig. 3

Spearman rank correlations between ALK7 and INHBB transcript levels and clinical traits in lean (n = 90) and obese (n = 90) subjects. Correlation coefficients (r) and their 95% confidence intervals, as derived from Fisher’s z-transformation, are represented by vertical marks and horizontal lines, respectively. Correlations are statistically significant if their confidence interval does not include zero (vertical axes). Corr. Diff. indicates whether correlations between clinical parameters and ALK7 or INHBB were significantly different between lean and obese subjects. Differences in r between lean and obese are significant if either confidence interval does not include r of the other.

Fig. 4

Correlations between INHBB and ALK7 gene expression. (A) The relation between INHBB and ALK 7 in lean (n = 90) and obese (n = 90) siblings. (B) The relation between INHBB and ALK7 in subjects in the highest quartile (n = 44) with respect to serum insulin levels compared to the rest of the group (n = 134). The slopes for the relation between INHBB and ALK7 expression were significantly different in lean and obese (p < 0.001) as well as between subjects in the highest quartile with respect to serum insulin levels compared to the rest of the group (p < 0.001). Data are standardized to mean = 0 and SD = 1.