Obesity is a worldwide growing epidemic. The arcuate nucleus of the hypothalamus (ARC) comprises the first order neurons such as proopiomelanocortin (POMC)- and agouti-related protein-expressing neurons signaling to various extra-hypothalamic and hypothalamic cells, such as oxytocin neurons within the paraventricular nucleus (PVH). In this presentation, I aim to demonstrate how pharmacological in vivo reductionist approach led us to identification of microRNAs such as miR-29 critical for a proper metabolic balance. Moreover, in situ CRISPR-Cas9-dependent inactivation of this microRNA in POMC neurons or glucocorticoid receptor in oxytocin neurons resulted in hyperphagia and obesity accompanied by insulin resistance, imbalanced fat/lean distribution as well as other metabolic changes. Importantly, identification and validation of the downstream targets allowed us to develop approaches to rescue these metabolic phenotypes.

SPEAKER BIOGRAPHY

After graduation from the Medical faculty of the Moscow State University in 2003, Ilya A. Vinnikov has earned his doctoral degree in 2008 at the University of Heidelberg. The following postdoc training was obtained at the German Cancer Research Center (DKFZ) Heidelberg. Since 2016, he is a tenure track associate professor of the School of Life Sciences and Biotechnology at the Shanghai Jiao Tong University. The main research interests of Prof. Vinnikov’s Laboratory of Molecular Neurobiology comprise deciphering the mechanisms of genetic, epigenetic, transcriptional and post-transcriptional regulation of biological systems and understanding their physiological relevance in the evolutionary context. His studies on diabetes mellitus, obesity and neurodegeneration were published in Nature Medicine, Journal of Neuroscience, Cell Death and Disease, Molecular Metabolism and other journals. The lab uses in situ Cre-dependent CRISPR-Cas9-based genetic approaches and other genetic, epigenetic and pharmacological tools with high cellular and molecular resolution to manipulate the genes of interest in specific cell populations of mice and nematodes. Vinnikov’s research group was the first to demonstrate an age-related decline of microRNAs and their critical physiological role in dopamine neurons. Moreover, in their recent works, they used an originally developed stabilized microRNA mimics delivery reductionist approach to identify hypothalamic microRNAs protecting mice from obesity. The integrated solutions developed by Vinnikov lab to monitor and analyze metabolic and age-related parameters by implantable sensors will help translate these research findings to patients.