Diet-induced miRNAs regulate adult neurogenesis and functional activity of nascent neurons in the hypothalamus

Abstract

AbstractNeurogenesis in the hypothalamus upon high fat diet (HFD) feeding regulates the feeding circuit. HFD induces the neurogenesis of β2 tanycytes in young-adult mice. However molecular mechanisms of tanycytic neurogenesis; and their functional integration into the feeding circuitry are poorly understood. We investigated the role of miRNAs in the regulation of HFD-induced tanycytic neurogenesis. miRNA arrays identified a cohort of HFD-induced, differentially-regulated miRNAs in BrdU+β2-tanycytes. These miRNAs arise from different chromosomes, rather than a single cluster.In siliconetwork analysis on the predicted targets of all five HFD-induced miRNAs and reporter assays identified a subset of targets that influence neurogenesis and neuronal differentiation. HFD-induced miRNAs drive a molecular program leading to the functional integration of nascent neurons; introduction of a miRNA sponge sequestering all five miRNAs abolishes it. Diet-regulated newborn neurons preferentially differentiate into AgRP+ neurons that functionally integrate into the feeding circuit.