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

Figures

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  Fig. 1. Effect of phytoformulation on (A) body weight, (B) heart-to-body weight ratio, (C) food intake and adipose tissue development (D) epididymal, (E) subcutaneous, (F) blood glucose level, (G) insulin and (H) IR in HFD-induced OCM rats. Values are expressed as mean ± SD, ∗P˂0.05.

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  Fig. 2. Effect of phytoformulation on serum hyperlipidemia markers (A) total cholesterol (B) triglycerides, (C) LDL, (D) HDL and (E) free fatty acids in obese rats. The phytoformulation suppressed the accumulation of lipids (F) total cholesterol, (G) triglycerides, (H) free fatty acids and increased the content of (I) phospholipids in the heart of obese rats. Values are expressed as mean ± SD, ∗P˂0.05.

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  Fig. 3. Phytoformulation suppressed the production of proinflammatory cytokines (A) C-reactive protein, (B) fibrinogen, and (C) homocysteine in obese rats. Values are expressed as mean ± SD, ∗P˂0.05.

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  Fig. 4. The histopathological findings of the cardiac tissue of the control and experimental groups, (A) the normal control group showed normal structure of cardiomyocytes and muscle fibres, (B) the OCM control showed the remarkable pathological signs induced by HFD supplementation, (C) OCM + phytoformulation and (D) OCM + lorcaserin showed no significant histopathological abnormalities. H&E, scale bar = 40 μm, 40X. The graphs show the (E) the percentage of interstitial fibrosis and (F) the pathology score based on the severity of histopathological changes in the different groups, marked with <0.5 points (no changes), 1 (negligible), 2 (mild), 3 (moderate), >4 (severe). MC: Muscle fibres, S: the intracellular spaces, Yarrow: vesicular nuclei, Arrowhead: damage to cardiac muscle fibers, Curved yarrow: separation of cardiac muscle fibres, Dot Yarrow: inflammatory cells, Dash dot yarrow: fatty degeneration. Values are expressed as mean ± SD, ∗P˂0.05.

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  Fig. 5. Phytoformulation downregulated genes (A) SREBF1, (B) FAS, (C) ACC, responsible for fatty acid synthesis, and gene (D) FABP1, responsible for fatty acid uptake in the heart of HFD-induced OCM rats. The phytoformulation suppressed the cardiac lipid accumulation by upregulating the genes (E) LAL, (F) HSL, and (G) LPL and (H) PPAR-α, which are responsible for fatty acid catabolism in HFD-induced OCM rats. Values are expressed as mean ± SD, ∗P˂0.05.

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  Fig. 6. Phytoformulation inhibits inflammation and apoptosis in the heart of HFD-induced OCM rats by regulating mRNA expressions of (A) NF-kB, (B) TNF-α, (C) IL-6, (D) TLR-4, (E) BaX and (F) caspase-3. Values are expressed as mean ± SD, ∗P˂0.05.

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  Fig. 7. A proposed mechanism for the effect of phytoformulation on HFD-induced OCM. Phytoformulation regulates mRNA expressions of LAL, HSL, PPAR-α and LPL, thereby enhancing fatty acid catabolism. At the same time, the phytoformulation down-regulates mRNA expression of SREBF1, FAS, ACC and FABP1, leading to suppression of fatty acid synthesis and uptake in the heart. Subsequently, the phytoformulation attenuated apoptosis and inflammation by decreasing mRNA expressions of NF-kB, TNF-α, IL-6, TLR-4, BaX and caspase-3 in cardiomyocytes. Therefore, it is hypothesized that the phytoformulation may be able to prevent cardiac lipid deposition by regulating fatty acid metabolism and subsequently controlling NF-kB/TLR4/BaX/caspase-3 signalling and attenuating inflammation and apoptosis in the heart.