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

Abstract

Visceral obesity is more closely associated with many deleterious metabolic sequelae than obesity per se. The identification 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 significantly overexpressed in omental (Om) compared with subcutaneous (Sc) adipocytes. This molecule is involved in the TNFalpha signalling pathway and may inhibit apoptosis. To examine the effect of serum agents and TNFalpha upon cIAP2 mRNA expression in human primary culture preadipocytes. 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 TNFalpha for 4 h and mRNA levels analysed by quantitative reverse-transcription polymerase chain reaction. When human preadipocytes were cultured in a defined 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>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 TNFalpha induced a large increase in mRNA levels of cIAP2 (mean 20-fold). These results demonstrate that cIAP2 is expressed in a depot-specific manner in human preadipocytes and that levels of expression are regulated by serum factors and TNFalpha. 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.