Adipose depot-specific expression of cIAP2 in human preadipocytes and modulation of expression by serum factors and TNFα

Abstract

BACKGROUND: Visceral obesity is more closely associated with many deleterious metabolic sequelae than obesity per se. The identi®cation of properties that distinguish fat cells of the omentum from adipocytes situated elsewhere in the body may lead to the development of therapeutic strategies targeting visceral obesity. We have previously demonstrated that cIAP2 mRNA is signi®cantly overexpressed in omental (Om) compared with subcutaneous (Sc) adipocytes. This molecule is involved in the TNFa signalling pathway and may inhibit apoptosis. OBJECTIVE: To examine the effect of serum agents and TNFa upon cIAP2 mRNA expression in human primary culture preadipocytes. DESIGN: Paired omental and subcutaneous adipose tissue biopsies were obtained from 11 patients, nine female and two male, with ages ranging from 29 to 82. These were cultured in either serum containing medium or serum-free medium with or without the addition of TNFa for 4 h and mRNA levels analysed by quantitative reverse-transcription polymerase chain reaction. RESULTS: When human preadipocytes were cultured in a de®ned medium containing foetal calf serum the Om cells had a greater level of expression of cIAP2 mRNA than Sc cells from the same individual (mean 3.5-fold higher Sc b Om; P`0.01). However, when serum was removed from this media for a transitory period the level of cIAP2 mRNA decreased in the omental depot such that Sc preadipocytes had greater cIAP2 expression than their Om counterparts. Addition of TNFa induced a large increase in mRNA levels of cIAP2 (mean 20-fold).CONCLUSIONS: These results demonstrate that cIAP2 is expressed in a depot-speci®c manner in human preadipocytes and that levels of expression are regulated by serum factors and TNFa. Thus there may be intrinsic differences between preadipocyte cells from different adipose depots and this may play a role in the regulation of body fat distribution via the modulation of fat cell apoptosis.

Expression of cellular inhibitor of apoptosis protein-2 in human subcutaneous and omental adipose tissue

“…The same authors also showed that cIAP2 mRNA expression is higher in human preadipocytes from OM than that from SC fat. 15 However, their study focused only on mRNA levels. As mRNA expression does not always reflect protein expression or the concentration of the fully processed protein, we extended the observation by certifying that the principal difference between OM and SC adipose tissue occurs also on the protein level.…”

“…When compared with human isolated adipocytes, preadipocytes cultured in serum containing medium have higher cIAP2 mRNA levels and also lower sensitivity to TNFa-induced apoptosis. 14,15,17 Therefore, the expression of cIAP2 in SC and OM adipose tissue may reflect depot-specific susceptibility to apoptosis, and thereby adipose tissue loss or deposition.…”

“…13 Two other studies reported that cIAP2 mRNA is expressed in depotspecific manner in adult human adipose cells. 14,15 So far, research on difference in gene expression has focused on adults. Very little is known about site-related gene expression in adipose tissue of children.…”

Identification of genes expressed differentially in subcutaneous and visceral fat of cattle, pig, and mouse

“…differential display and reverse transcriptase-polymerase chain reaction; fat depot THERE ARE TWO TYPES OF ADIPOSE TISSUE, subcutaneous and visceral. Recent studies indicate that adipocytes in these two fat depots show differences in basal metabolic properties, for example, in regulating volume, lipid composition, and so on (22,24). There is considerable current interest in visceral adipose tissue because of its relationship with various diseases such as cardiovascular disease, type 2 diabetes mellitus, hyperlipidemia, and syndrome X.…”

“…There are a number of potential reasons why visceral adipose tissue may contribute to abnormalities in metabolism; among these are its anatomical site and pattern of venous drainage, and the presence of intrinsic and unique features of visceral adipocytes. The venous drainage of visceral adipose tissue is via the portal system, directly providing free fatty acid as a substrate for hepatic lipoprotein metabolism and glucose production (16,22,24). Additionally, in vitro studies using labeled tracers have demonstrated that visceral adipocytes have higher rates of lipid turnover than subcutaneous adipose tissue (19,20).…”