Islet-1: A Potentially Important Role for an Islet Cell Gene in Visceral Fat

Abstract

To examine differences in gene expression between visceral (VF) and subcutaneous fat (SF) to identity genes of potential importance in regulation of VF. We compared gene expression (by DNA array and quantitative PCR (qPCR)) in paired VF and SF adipose biopsies from 36 subjects (age 54 +/- 15 years, 15 men/21 women) with varying degrees of adiposity and insulin resistance, in chow and fat fed mice (+/- rosiglitazone treatment) and in c-Cbl(-/-) mice. Gene expression was also examined in 3T3-L1 preadipocytes during differentiation. A twofold difference or more was found between VF and SF in 1,343 probe sets, especially for genes related to development, cell differentiation, signal transduction, and receptor activity. Islet-1 (ISL1), a LIM-homeobox gene with important developmental and regulatory function in islet, neural, and cardiac tissue, not previously recognized in adipose tissue was virtually absent in SF but substantially expressed in VF. ISL1 expression correlated negatively with BMI (r = -0.37, P = 0.03), abdominal fat (by dual energy X-ray absorptiometry, r = -0.44, P = 0.02), and positively with circulating adiponectin (r = 0.33, P = 0.04). In diet-induced obese mice, expression was reduced in the presence or absence of rosiglitazone. Correspondingly, expression was increased in the c-Cbl(-/-) mouse, which is lean and insulin sensitive (IS). ISL1 expression was increased sevenfold in 3T3-L1 preadipocytes during early (day 1) differentiation and was reduced by day 2 differentiation. An important developmental and regulatory gene ISL1 is uniquely expressed in VF, probably in the preadipocyte. Our data suggest that ISL1 may be regulated by adiposity and its role in metabolic regulation merits further study.