Abstract
People with upper body or visceral obesity have a much higher risk of morbidity and mortality from obesity-related metabolic disorders than those with lower body obesity. In an attempt to develop therapeutic strategies targeting visceral obesity, depot- specific differences in the expression of genes in omental and subcutaneous adipose tissues were investigated by DNA array technology, and their roles in adipocyte differentiation were further examined. We found that levels of metallothionein-II (MT-II) mRNA and protein expression were higher in omental than in subcutaneous adipose tissues. The study demonstrates that MT-II may play an important role in adipocyte differentiation of 3T3L1 preadipocytes, and that N-acetylcysteine (NAC) inhibits the adipocyte differentiation of 3T3L1 cells by repressing MT-II in a time- and dose-dependent manner. Furthermore, the intraperitoneal administration of NAC to rats and mice resulted in a reduction of body weights, and a marked reduction in visceral fat tissues. These results suggest that MT-II plays important roles in adipogenesis, and that NAC may be useful as an anti-obesity drug or supplement.
Highlights
Obesity is a ubiquitous health hazard in industrialized countries and is closely associated with a number of pathological disorders, e.g., non-insulindependent diabetes, hypertension, cancer, gallbladder disease, and atherosclerosis (Gregoire et al, 1998)
The levels of MT-II expression, induced during adipose differentiation, were found to be downregulated by NAC in a dose- and time-dependent manner (Figure 4). These results suggest that MT-II plays an important role in the adipocyte differentiation of 3T3L1 cells and that NAC is utilized to inhibit adipose differentiation in animal models
This study shows that levels of MT-II mRNA and of MT protein expression are elevated in omental adipose tissues versus subcutaneous adipose tissues
Summary
Obesity is a ubiquitous health hazard in industrialized countries and is closely associated with a number of pathological disorders, e.g., non-insulindependent diabetes, hypertension, cancer, gallbladder disease, and atherosclerosis (Gregoire et al, 1998). Obesity-associated disorders are known to be closely associated with the degree of excess adipose tissue and with the distribution of body fat (Bjorntorp, 1996). Visceral (omental) and subcutaneous adipose tissues are morphologically and functionally different, which may contribute to the increased morbidity associated with visceral obesity. A variety of metabolic differences such as fatty acid turnover, lipolysis (van Harmelen et al, 2002), and the effectiveness of insulin action, in omental and subcutaneous adipose tissues have been reported (Wajchenberg et al, 2002). Roles of MTs during adipocyte differentiation and of their regional preferences for omental and subcutaneous adipose tissues are not understood. We found that N-acetylcysteine (NAC) inhibits the adipocyte differentiation of 3T3L1 cells by repressing MT-II in a dose- and time-dependent manner. Animal studies showed that NAC reduced body weights, especially by decreasing the visceral fat tissue amounts
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