Adipose tissue specific adipose triglyceride lipase influences the development of pressure overload-induced heart failure

Introduction: Cardiac metabolism undergoes changes in response to pathological hypertrophy (PH), characterized by increased reliance on glucose and decreased free fatty acid (FFA) oxidation. Also cardiac metabolism is influenced by other organs such as adipose tissue (AT). We aimed to investigate the effect of Adipose Triglyceride Lipase (ATGL) in AT on the development of PH in a pressure overload-induced cardiac hypertrophy model in mice.

Methods: Adipose tissue specific ATGL-knock out (atATGL-KO) and wild type mice (WT) underwent transverse aortic constriction (TAC) or sham surgery.

We performed echocardiography one week before and 11 weeks after surgery. Left ventricular mass (LVM) and ejection fraction (EF%) were calculated. Insulin sensitivity was assessed by intraperitoneal glucose (ipGTT) and insulin tolerance test (ipITT). FFAs were measured in serum.

Results: LVM in WT was significantly higher compared to atATGL-KO after TAC (LVM/TL [mg/mm] WT: 18,0 ± 2,2; KO: 13,1 ± 2,3; p < 0,01). EF% was significantly more reduced in WT compared to KO ([%] WT: 28,81 ± 6,9 KO: 42,39 ± 4,5; p < 0,01).

IpGTT and ipITT revealed that KO TAC had higher insulin sensitivity compared to WT TAC (AUC; p < 0.001 and p < 0.05 respectively). Serum FFA-levels were higher in WT than in KO (p < 0,001).

Conclusion: In this study, we demonstrate that atATGL is crucial for the development of pressure overload-induced PH. The lack of ATGL in adipose tissue, the associated reduced lipolysis and the subsequent switch in cardiac metabolism from FFA oxidation to glycolysis are potential underlying mechanisms of this process.