Microvesicle-shuttled miR-130b reduces fat deposition in recipient primary cultured porcine adipocytes by inhibiting PPAR-g expression.

ABSTRACT

Obesity is a worldwide epidemic, and a risk factor for cardiovascular disease and type 2 diabetes. Consequently, the development of safe and effective anti-obesity drugs is an area of ongoing clinical interest. MicroRNAs play a vital role in anti-obesity by inhibiting the expression of genes involved in adipogenesis and lipogenesis. However, the clinical application of miRNAs has been limited by a lack of appropriate delivery systems. The discovery of microvesicles (MVs) has shed new light on the search for more efficient drug transport tools. In a previous study, we demonstrated that miRNA-130b suppressed fat deposition by inhibiting PPAR-g expression. In order to demonstrate whether miRNA-130b can be packaged into MVs and function as an endogenous form of miRNA-130b in recipient cells, we transfected HeLa-229 cells with plasmid to overexpress miRNA-130b. This enabled HeLa-229 cells to selectively package miRNA-130b into MVs and actively secrete the miRNA-130b enriched MVs into the culture media. We further verified that MVs enriched with miRNA-130b contain elevated concentrations of Argonaute 2 and heat shock protein 90a which are known to protect the circulating miRNAs from degradation. Exposure of primary cultured porcine adipocytes to purified, miRNA-130b-enriched MVs resulted in a significant down-regulation of PPAR-g expression which was associated with reduced adipogenesis and lipogenesis. Taken together, our results suggest that MVs may provide an effective transport systems for the deliver of miRNAs for therapeutic use. We also showed that MV-shuttled miRNA-130b inhibited adipogenesis and lipogenesis, and reduced fat deposition in recipient adipocytes by targeting PPAR-g.