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SHR Neuro Cancer Cardio Lipid Metab Microb

Kolleritsch, S; Pajed, L; Tilp, A; Hois, V; Pototschnig, I; Kien, B; Diwoky, C; Hoefler, G; Schoiswohl, G; Haemmerle, G.
Adverse cardiac remodeling augments adipose tissue ss-adrenergic signaling and lipolysis counteracting diet-induced obesity
J BIOL CHEM. 2023; 299(6): 104788 Doi: 10.1016/j.jbc.2023.104788 [OPEN ACCESS]
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Leading authors Med Uni Graz: Schoiswohl Gabriele Maria
Co-authors Med Uni Graz: Diwoky Clemens; Höfler Gerald; Hois-Zelinka Victoria; Kien Benedikt
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Abstract:: Cardiac triacylglycerol accumulation is a common charac-teristic of obesity and type 2 diabetes and strongly correlates with heart morbidity and mortality. We have previously shown that cardiomyocyte-specific perilipin 5 overexpression (Plin5-Tg) provokes significant cardiac steatosis via lowering cardiac lipolysis and fatty acid (FA) oxidation. In strong contrast to cardiac steatosis and lethal heart dysfunction in adipose tri-glyceride lipase deficiency, Plin5-Tg mice do not develop heart dysfunction and show a normal life span on chow diet. This finding prompted us to study heart function and energy meta-bolism in Plin5-Tg mice fed high-fat diet (HFD). Plin5-Tg mice showed adverse cardiac remodeling on HFD with heart function only being compromised in one-year-old mice, likely due to reduced cardiac FA uptake, thereby delaying deleterious cardiac lipotoxicity. Notably, Plin5-Tg mice were less obese and pro-tected from glucose intolerance on HFD. Changes in cardiac energy catabolism in Plin5-Tg mice increased ss-adrenergic signaling, lipolytic, and thermogenic protein expression in ad-ipose tissue ultimately counteracting HFD-induced obesity. Acute cold exposure further augmented ss-adrenergic signaling in Plin5-Tg mice, whereas housing at thermoneutrality did not protect Plin5-Tg mice from HFD-induced obesity albeit blood glucose and insulin levels remained low in transgenic mice. Overall, our data suggest that the limited capacity for myocar-dial FA oxidation on HFD increases cardiac stress in Plin5-Tg mice, thereby stimulating adipose tissue ss-adrenergic signaling, triacylglycerol catabolism, and thermogenesis. How-ever, long-term HFD-mediated metabolic stress causes con-tractile dysfunction in Plin5-Tg mice, which emphasizes the importance of a carefully controlled dietary regime in patients with cardiac steatosis and hypertrophy.