Journal Article

Plin2-deficiency reduces lipophagy and results in increased lipid accumulation in the heart

Redfors, Björn, Andersson, Linda, Tomas Dalen, Knut, Miljanovic, Azra, Borén, Jan, Omerovic, Elmir, Levin, Malin C., Nair, Syam, Ståhlman, Marcus, Klevstig, Martina, Drevinge, Christina, Levin, Max, Ekstrand, Matias, Fogelstrand, Per, Mardani, Ismena, Scharin Täng, Margareta, Kimmel, Alan R.

2019

Overview

Myocardial dysfunction is commonly associated with accumulation of cardiac lipid droplets (LDs). Perilipin 2 (Plin2) is a LD protein that is involved in LD formation, stability and trafficking events within the cell. Even though Plin2 is highly expressed in the heart, little is known about its role in myocardial lipid storage. A recent report shows that cardiac overexpression of Plin2 result in massive myocardial steatosis suggesting that Plin2 stabilizes LDs. In this study, we hypothesized that deficiency in Plin2 would result in reduced myocardial lipid storage. In contrast to our hypothesis, we found increased accumulation of triglycerides in hearts, and specifically in cardiomyocytes, from Plin2 −/− mice. Although Plin2 −/− mice had markedly enhanced lipid levels in the heart, they had normal heart function under baseline conditions and under mild stress. However, after an induced myocardial infarction, stroke volume and cardiac output were reduced in Plin2 −/− mice compared with Plin2 +/+ mice. We further demonstrated that the increased triglyceride accumulation in Plin2-deficient hearts was caused by altered lipophagy. Together, our data show that Plin2 is important for proper hydrolysis of LDs.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/106 / 13/109 / 14 / 14/19 / 631/337 / 64/110 / 692/4017 / 82/80 / Accumulation / Animals / Autophagy / Cardiology and Cardiovascular Disease / Cardiomyocytes / Cell Respiration / Cerebral infarction / Heart / Heart - physiology / Heart diseases / Humanities and Social Sciences / Kardiologi och kardiovaskulära sjukdomar / Lipid Metabolism / Lipids / Male / Mice / Mice, Inbred C57BL / Mitochondria - metabolism / multidisciplinary / Myocardial infarction / Myocardium - cytology / Myocardium - metabolism / Myocytes, Cardiac - cytology / Myocytes, Cardiac - metabolism / Perilipin-2 - deficiency / Science / Science (multidisciplinary) / Steatosis / Triglycerides / Triglycerides - metabolism