Nanlan Luo, W. Timothy Garvey, Da-Zhi Wang and Yuchang Fu
Background: MicroRNAs (miRNAs) have emerged as an important class of small molecules that regulate a spectrum of biological processes. However, their roles in the regulation of lipid metabolism and inflammatory response in metabolic syndrome are not completely known. To identify miRNAs and investigate how they are involved in lipid metabolism and inflammatory response in cells and animals and define the function and regulatory mechanism of these microRNAs.
Methods and results: We stimulated human THP-1 macrophages with oxLDL and found that one of the miRNAs, miR-150, strongly responded to the lipid accumulation and inflammatory response in these cells. Overexpression of miR-150 in macrophage cells resulted in an increase in lipid accumulation, accompanying with a high expression of several pro-inflammatory cytokines. Conversely, when miR-150 knockout mice were challenged with a high fat diet, these mice presented reduced whole body weight with less fat accumulation, improved systemic glucose tolerance and insulin sensitivity. The expression of pro-inflammatory cytokines in the insulin target adipose tissues was reduced in miR-150 null mice. We identified Adiponectin receptor 2 (AdipoR2) as a potential miR-150 target gene and suggested it may play an important role in miR-150-mediated lipid metabolism and inflammatory response.
Conclusions: These results uncovered novel functions for miR-150 in modulating lipid metabolism and inflammatory response by regulating genes linked to lipid accumulation and related inflammation and provided a firm mechanistic explanation with characterization and determination of critical miR-150 for its associations with the metabolic diseases. These studies will highly impact and benefit metabolic disease research both in vitro and in vivoPDF
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