Fit despite fat: Researchers at the University of Graz have shown that inhibiting fat reduction protects the heart

In the latest study, Stephanie Kolleritsch from Guenter Haemmerle’s research group investigated mice that produced too much of Perilipin 5 (PLIN5) in the heart due to a genetic alteration. „Overexpression of PLIN5 in the heart muscle inhibits fat catabolism, which led to massive fatty deposition in the heart of our mice“, reports Haemmerle. What surprised the researchers: the organ continued to function normally anyway. “Although the heart muscle became thicker, the volume of the heart chamber increased at the same time. The mice suffered no functional restriction, nor was their lifespan shortened. This suggests that cardiac insufficiency resulting from obesity and type II diabetes is not caused by fat stored in the form of triglycerides, but rather by toxic products from increased fat catabolism”, says the molecular biologist. These new findings confirm those of previous studies.

When too many fatty acids enter the heart through the intake of food, the metabolic system reaches its limits and starts to make mistakes. Some of the fatty acids are not completely oxidised and have to be deposited within lipids such as triglycerides and ceramides. “Ceramides and a surplus of free fatty acids can be toxic and damage mitochondria, which are responsible for energy production”, explains Haemmerle. Inhibiting fat catabolism saved the mice in the Graz study from these negative effects.
Yet another connection could be relevant for the heart’s functioning: “By limiting the reduction of fat, the organ has to switch to glucose utilization for energy production. This is more energy-efficient – and better for the heart”, adds the bioscientist.
The new findings contribute significantly to our understanding of fat and energy metabolism in the heart and can therefore also be of interest for new therapy options.

contact for scientific information:
Assoc. Univ.-Prof. Dr. Günter Haemmerle
Institute of Molecular Biosciences, University of Graz, Austria
Tel.: 0043 316/380-8609
e-mail: guenter.haemmerle@uni-graz.at

original publication:
Low cardiac lipolysis reduces mitochondrial fission and prevents lipotoxic heart dysfunction in Perilipin 5 mutant mice
Stephanie Kolleritsch, Benedikt Kien, Gabriele Schoiswohl, Clemens Diwoky, Renate Schreiber, Christoph Heier, Lisa Katharina Maresch, Martina Schweiger, Thomas O. Eichmann, Sarah Stryeck, Petra Krenn, Tamara Tomin, Dagmar Kolb, Thomas Rülicke, Gerald Hoefler, Heimo Wolinski, Tobias Madl, Ruth Birner-Gruenberger, Guenter Haemmerle
Cardiovasc Res. 2019 May 6
DOI: 10.1093/cvr/cvz119

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