MicroRNA miR-7 and miR-17-92 in the Arcuate Nucleus of Mouse Hypothalamus Regulate Sex-Specific Diet-Induced Obesity.

Proper appetite, energy expenditure, and glucose and fat metabolisms are regulated by neurons in the arcuate nucleus (ARC) of mammalian hypothalamus. Studies have shown sex-specific difference in diet-induced obesity, but the underlying mechanisms remain unclear. Here, we show that microRNA (miRNA) miR-7 and miR-17-92 are expressed in proopiomelanocortin (POMC)-expressing neurons in the mouse ARC. Specific knockdown of miR-7 and knockout of miR-17-92 in POMC-expressing neurons aggravate diet-induced obesity only in females and males, respectively. Sex-differentially expressed genes are identified in the male and female ARC of wild-type adult mice using RNA sequencing. Interestingly, some target genes for miR-7 and miR-17-92 not only display sex-differential expression in the male and female ARC but also respond to high-fat diet treatment in miR-7 knockdown and miR-17-92 knockout mice. Our results demonstrate an important role of miRNAs in regulating sex-specific diet-induced obesity, likely through modulating expression of target genes that show sex-differential expression in the ARC of the hypothalamus.