Identification of Novel Genes Differentially Expressed in Omental Fat of Obese Subjects and Obese Type 2 Diabetic Patients

Abstract

Obesity is associated with an increased risk for developing type 2 diabetes, insulin resistance, hypertension, dyslipidemia, cardiovascular disease, respiratory dysfunction, and certain forms of cancer. Insulin resistance in many type 2 diabetic patients is the result of increased visceral adiposity. To identify novel genes implicated in type 2 diabetes and/or obesity and to elucidate the molecular mechanisms underlying both diseases, we analyzed gene expression in omental fat from lean and obese nondiabetic subjects and obese type 2 diabetic patients using mRNA differential display and subtracted library techniques. After screening over 13,800 subtracted cDNA clones and 6,912 cDNA amplification products, we identified 2,078 cDNAs that showed potential differential expression in the omental fat of lean versus obese nondiabetic subjects versus obese type 2 diabetic patients. Data analysis showed that 70.7% of these clones corresponded to unknown genes (26.7% matched express sequence tags [ESTs]) and 29.3% corresponded to known genes. Reverse Northern and classic Northern analyses further confirmed that the expression of five of these cDNA clones was elevated in obese nondiabetic subjects and obese type 2 diabetic patients. Four candidate genes were further evaluated for tissue distribution, which showed expression primarily in adipose and skeletal muscle tissue, and chromosomal localization. We concluded that both mRNA differential display and subtracted cDNA libraries are powerful tools for identifying novel genes implicated in the pathogenesis of obesity and type 2 diabetes.

RBP‐to‐retinol ratio, but not total RBP, is elevated in patients with type 2 diabetes

“…Yang et al reported that overexpression of RBP or injection of RBP in mice led to insulin resistance and suggested that circulating adipocyte-derived RBP might induce insulin resistance [1]. Upregulated messenger RNA (mRNA) expression of RBP in adipose tissue of patients with T2DM has been reported previously [13,14], although others have found no difference in RBP mRNA expression between insulin-sensitive and insulin-resistant subjects [15] or between obese and non-obese subjects [16]. However, we and others have reported diverging results with lower RBP in type 1 diabetes [17,18] as well as in T2DM [19,20].…”

Two Strategies to Identify Genes Underlying Complex Diseases

“…The differential display was successfully used to identify a novel polypeptide involved in the regulation of energy balance, which was differentially expressed in the hypothalamus of obese/diabetic and lean/nondiabetic Israeli sand rats [36]. In addition, Corominola and his colleagues confirmed that the expression of five cDNA clones was elevated in obese nondiabetic subjects and obese type 2 diabetic patients [37].…”

Epigenomics: Genome-Wide Study of Methylation Phenomena

“…In a mouse model of type-2 diabetes and obesity, progression from a lean state to obesity and overt hyperglycemia was associated with changes in gene expression inverse to those seen in adipocyte differentiation (Nadler et al, 2000). In a similar study in humans, gene expression was analysed in omental fat samples taken from lean and obese nondiabetic subjects and obese type-2 diabetic patients (Corominola et al, 2001). The authors identified some 2000 cDNAs that showed potential differential expression between each of these groups (Corominola et al, 2001).…”

“…In a similar study in humans, gene expression was analysed in omental fat samples taken from lean and obese nondiabetic subjects and obese type-2 diabetic patients (Corominola et al, 2001). The authors identified some 2000 cDNAs that showed potential differential expression between each of these groups (Corominola et al, 2001). Furthermore, the upregulation of several genes, in response to insulin, was completely abrogated in type-2 diabetic patients compared to control subjects, insulinresistant nondiabetic obese patients, and hyperglycemic type-1 diabetic subjects (Ducluzeau et al, 2001).…”