Expression of lipogenic genes is upregulated in the heart with exercise training-induced but not pressure overload-induced left ventricular hypertrophy

• Published in: American journal of physiology: endocrinology and metabolism 2013-06, Vol.304 (12), p.E1348-E1358
• Main Authors: Dobrzyn, Pawel, Pyrkowska, Aleksandra, Duda, Monika K, Bednarski, Tomasz, Maczewski, Michal, Langfort, Jozef, Dobrzyn, Agnieszka
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Cardiovascular disease; Exercise; Fatty Acids - metabolism; Gene expression; Gene Expression Regulation - physiology; Heart; Heart - physiology; Hypertrophy, Left Ventricular - diagnostic imaging; Hypertrophy, Left Ventricular - genetics; Hypertrophy, Left Ventricular - physiopathology; Lipase - genetics; Lipase - metabolism; Lipids; Lipogenesis - genetics; Lipogenesis - physiology; Male; Physical Conditioning, Animal - physiology; Physical Endurance - physiology; PPAR alpha - genetics; PPAR alpha - metabolism; Random Allocation; Rats; Rats, Wistar; Training; Ultrasonography; Up-Regulation - physiology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00603.2012

Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling. Additionally, FA oxidation pathways regulated by AMP-activated protein kinase (AMPK) and peroxisome proliferator activated receptor-α (PPARα) were induced in trained hearts. Cardiac lipid content was not changed by physiological stimulation, underlining balanced lipid utilization in the trained heart. Moreover, pathological hypertrophy induced the AMPK-regulated oxidative pathway, whereas PPARα and expression of its downstream targets, i.e., acyl-CoA oxidase and carnitine palmitoyltransferase I, were not affected by AAB. In contrast, pathological hypertrophy leads to cardiac triglyceride (TG) and diacylglycerol (DAG) accumulation, although the expression of lipogenic genes and the levels of FA transport proteins (CD36 and FATP) were not changed or reduced compared with the sham group. A possible explanation for this phenomenon is a decrease in lipolysis, as evidenced by the increased content of adipose triglyceride lipase inhibitor G0S2, the increased phosphorylation of hormone-sensitive lipase at Ser(565), and the decreased protein levels of DAG lipase that attenuate TG and DAG contents. The increased TG and DAG accumulation observed in AAB-induced hypertrophy might have lipotoxic effects, thereby predisposing to cardiomyopathy and heart failure in the future.