A-FABP potentiates obesity-related cardiac dysfunction and cardiomyopathy

Abstract

Background and objectives: Obesity cardiomyopathy is growing to be a key obesity implication as the obesity has become a great health problem. However, the primary cause to contribute to the development of cardiomyopathy of obesity has yet to be identified. It has been discovered by our groups that adipocyte fatty acid binding protein (A-FABP) is associated with obesity-related heart failure and the association between A-FABP and inflammatory cytokines. In this study, we investigated the role of A-FABP in obesity cardiomyopathy. Male A-FABP knockout (KO) mice and wild type (WT) littermates fed with either high fat high cholesterol (HFHC) or standard chow (STC) diet for 24 weeks were employed to explore the role of A-FABP in obesity cardiomyopathy. Key findings: 1. The circulating A-FABP level and its cardiac expression in the C57BL/6N mice were significantly elevated after 24 weeks of HFHC diet feeding comparing to the mice fed with STC diet. 2. A-FABP deficiency could ameliorate the HFHC diet-induced cardiac hypertrophy and cardiac fibrosis. 3. A-FABP deficiency alleviates HFHC diet-induced cardiac inflammation and ER stress by measuring the quantity of inflammatory markers (TNF-, MCP-1, IL6, IL-1) and ER stress (GRP78, CHOP) in KO-HFHC mice as compared to WT-HFHC mice. 4. The protective effect of A-FABP deficiency in diet-induced cardiomyopathy may be not related to the reduced cardiac TG accumulation.

Conclusion: A-FABP has an important role in regulating obesity-related cardiac dysfunction and cardiomyopathy by free fatty acids which could activate an inflammatory response in NF-B dependent signaling pathway, which further activates oxidative stress and ER stress.