Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart

Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.