Abstract
Rosiglitazone (RG) is a well-known activator of peroxisome proliferator-activated receptor-gamma (PPARγ) and used to treat hyperglycemia and type 2 diabetes; however, its clinical application has been confounded by adverse side effects. Here, we assessed the roles of chlorogenic acid (CGA), a phenolic secondary metabolite found in many fruits and vegetables, on the differentiation and lipolysis of mouse 3T3-L1 preadipocytes. The results showed that CGA promoted differentiation in vitro according to oil red O staining and quantitative polymerase chain reaction assays. As a potential molecular mechanism, CGA downregulated mRNA levels of the adipocyte differentiation-inhibitor gene Pref1 and upregulated those of major adipogenic transcriptional factors (Cebpb and Srebp1). Additionally, CGA upregulated the expression of the differentiation-related transcriptional factor PPARγ2 at both the mRNA and protein levels. However, following CGA intervention, the accumulation of intracellular triacylglycerides following preadipocyte differentiation was significantly lower than that in the RG group. Consistent with this, our data indicated that CGA treatment significantly upregulated the expression of lipogenic pathway-related genes Plin and Srebp1 during the differentiation stage, although the influence of CGA was weaker than that of RG. Notably, CGA upregulated the expression of the lipolysis-related gene Hsl, whereas it did not increase the expression of the lipid synthesis-related gene Dgat1. These results demonstrated that CGA might function as a potential PPARγ agonist similar to RG; however, the impact of CGA on lipolysis in 3T3-L1 preadipocytes differed from that of RG.
Highlights
Diabetes mellitus is a chronic degenerative metabolic disease that seriously affects human health and has reached epidemic proportions over the last 30 years [1]
RG treatment upregulated Hsl levels by 44.0% to 93.7% and Dgat levels by 12.3% to 57.7% relative to those in control group. These results suggested that the reason chlorogenic acid (CGA) did not promote TAG accumulation might have been its upregulation of Hsl and lack of effect on Dgat expression
We investigated whether CGA could affect preadipocyte differentiation through its lipid-lowering effect, as well as the molecular mechanism associated with CGA-mediated adipogenesis
Summary
Diabetes mellitus is a chronic degenerative metabolic disease that seriously affects human health and has reached epidemic proportions over the last 30 years [1]. Concomitant with the prevalence of obesity and increased lifespan in industrial countries, the incidence of type 2 diabetes has risen rapidly worldwide [2], with the number of people suffering from diabetes globally expected to rise to >600 million within the 25 years [3]. China has the highest number of affected individuals, of whom 90% are afflicted with type 2 diabetes mellitus [4, 5]. RG causes a significant weight increase in overweight subjects with type 1 diabetes [8]. RG is still utilized to treat patients suffering from type 2 diabetes in China [9, 10], it has been withdrawn from
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