Insulin Resistance and Vulnerability to Cardiac Ischemia

• DOI: 10.2337/db18-0449
• Publication Date: 2018-09-26T15:22:03Z
• Authors: Tomas Jelenik; Ulrich Flögel; Elisa Álvarez-Her...; Daniel Scheiber; Elric Zweck; Zhaoping Ding; Maik Rothe; Lucia Mastrototaro; Vivien Kohlhaas; Jörg Kotzka; Birgit Knebel; Dirk Müller-Wieland; Sarah Moellendorf; Axel Gödecke; Malte Kelm; Ralf Westenfeld; Michael Roden; Julia Szendroedi
• Keywords: Steatosis; Lipotoxicity

Hepatic and myocardial ectopic lipid deposition has been associated with insulin resistance (IR) cardiovascular risk. Lipid overload promotes increased hepatic oxidative capacity, stress, impaired mitochondrial efficiency, driving the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that higher availability ischemia-induced cardiac dysfunction decreases efficiency. Mice adipose tissue–specific overexpression sterol element–binding protein 1c as model combined NAFLD-IR controls underwent reperfused acute infarcts (AMIs). Whereas indexes left ventricle (LV) contraction were similar in both groups at baseline, showed severe post-AMI, prominent LV reshaping end-diastolic end-systolic volumes. Hearts displayed hypertrophy, steatosis, IR due to 18:1/18:1-diacylglycerol–mediated kinase Cε (PKCε) activation. Myocardial acid–linked respiration stress increased, whereas efficiency was decreased. In humans, decreased biopsies related troponin levels, a marker integrity. Taken together, favor susceptibility dysfunction. The diacylglycerol-PKCε pathway reduced caused by lipotoxicity may contribute compensation noninfarcted region myocardium.