Ilya Vinnikov
University of Heidelberg, Germany
Title: Hypothalamic microRNAs suppress development of obesity
Biography
Biography: Ilya Vinnikov
Abstract
Obesity is a growing epidemic characterized by an excess of fat content in the body. The contribution of neuronal microRNAs in the central control of metabolism is poorly studied. Using either AAV-vector derived or tamoxifen-inducible CamKII dependent Cre recombinases, we show that Dicer-dependent loss of microRNAs in the ARC neurons causes mTOR pathway activation and an imbalance in the levels of neuropeptides, resulting in severe hyperphagic adiposity. Similarly, the activation of mTOR due to Pten deletion in the adult forebrain leads to comparable weight increase. Conversely, delivery of the mTORC1 inhibitor rapamycin or specific microRNA mimics; predicted to target the mTOR pathway components, attenuate adiposity in mice lacking the Dicer1 gene in the forebrain. Our data indicate that non-coding RNAs, expressed in the hypothalamus, might be involved in the body weight control also in humans, which may have implications for treatment of the obesity syndrome. We propose a mechanism, in which microRNAs in the ARC inhibit the excessive activation of the insulin pathway, thus protecting from hyperphagia and obesity.