Targeting Mitochondrial Pathways in Obesity and Type 2 Diabetes

Download or read book Targeting Mitochondrial Pathways in Obesity and Type 2 Diabetes written by Jessica Erin Sacks and published by . This book was released on 2018 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: Obesity is one of the largest medical epidemics our society faces today. There are over forty obesity-associated diseases that affect nearly every organ system in the body, including Type 2 Diabetes (T2D) and Non-Alcoholic Fatty Liver Disease (NAFLD). Insulin resistance is one of the hallmark characteristics underlying metabolic diseases, and mitochondrial dysfunction is believed to be a central player in this phenomenon, yet our understanding of the specific molecular mechanisms that serve as cause and consequence of defective mitochondria remain complex and elusive despite significant attention. In the studies presented in this dissertation, liver tissue isolated from a rat model of obesity-induced NAFLD and human subject-derived skeletal muscle cells revealed two distinct mechanisms by which mitochondrial dynamics may play a key role in regulating the progression of insulin resistance and cellular bioenergetics in obesity-related metabolic diseases. First, we found that markers of mitochondrial fusion and biogenesis are upregulated in the liver of obese Sprague-Dawley rats following gastric bypass surgery, and expression of a specific fusion marker, namely mitofusin 1, is associated with reductions in body weight and improved insulin sensitivity. Utilizing human primary skeletal muscle cells isolated from percutaneous needle biopsy, we found that metformin treatment in vitro upregulates glycolytic pathways, suppresses mitochondrial respiration, and activates a specific protein of mitochondrial fission. Together, the work presented here describes mitochondrial mechanisms related to insulin resistance in two obesity models and major metabolic tissues.