Abstract
Obesity is a major risk factor for many chronic diseases, including diabetes, fatty livers, and cancer. Expansion of the adipose mass has been shown to be related to adipogenic differentiation of adipose-derived mesenchymal stem cells (ASCs). However, the underlying mechanism of this effect has yet to be elucidated. We found that osteopontin (OPN) is downregulated in ASCs and adipose tissues of obese mice and overweight human beings because of methylation on its promoter, indicating that OPN may affect the development of obesity. Silencing of OPN in wild-type ASCs promotes adipogenic differentiation, while reexpression of OPN reduced adipogenic differentiation in OPN−/− ASCs. The role of extracellular OPN in ASC differentiation was further demonstrated by supplementation and neutralization of OPN. Additionally, OPN suppresses adipogenic differentiation in ASCs through the C/EBP pathways. Consistent with these in vitro results, by intravenous injection of OPN-expressing adenovirus to the mice, we found OPN can delay the development of obesity and improve insulin sensitivity. Therefore, our study demonstrates an important role of OPN in regulating the development of obesity, indicating OPN might be a novel target to attenuate obesity and its complications.
Highlights
Prevalence of obesity and obesity-associated metabolic problems has become a major economic and medical burden worldwide [1, 2]
The results showed that OPN mRNA and secreted OPN protein in adipose-derived mesenchymal stem cells (ASCs) were significantly lower in high-fat diet (HFD) mice than in chow diet (CD) mice (Figures 1(b) and 1(c))
According to the World Health Organization (World Health Organization, 2000), and found similar results with that in mice (Figures 1(d) and 1(e)). These results demonstrated that the expression of OPN was decreased in adipose tissues and ASCs from both HFD mice and overweight people, suggesting an important role of OPN in obesity
Summary
Prevalence of obesity and obesity-associated metabolic problems has become a major economic and medical burden worldwide [1, 2]. Obesity is a key risk factor for the development of type 2 diabetes mellitus (T2DM), cancer, and cardiovascular disease [3]. White adipose tissue (WAT), the major type of adipose tissues, functions as a storage depot of lipids [5, 6]. WAT is an endocrine organ secreting adipokines which plays key roles in the pathogenesis of obesity and its complications [7, 8]. The adipose tissue constitutes almost half the body weight, making it the largest endocrine organ in human beings. Even minor metabolic changes in such a large secretory organ have the potential to affect broadly the entire body [9].
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