High‐Fat Induces Cardiac Remodeling via Dysbiosis of the Gut Microbiome

Abstract

Although consumption of a high‐fat diet (HFD) causes metabolic changes, the mechanisms remain unknown. We hypothesize that HFD instigates dysbiosis, and cardiac muscle remodeling by inducing matrix metalloproteinases (MMPs) that lead to an increase in the white fat contents in the body, and an intervention with a probiotic (PB) reverses these phenomena, in part, by increasing lipolysis (PGC‐1α, and UCP1), fat‐browning, and decreasing lipogenesis. To test this hypothesis, we used wild type (WT) mice and fed them with HFD for a period of 16‐weeks with or without a PB in the drinking water. Cardiac injury was measured by estimating the CKMB activity. The results demonstrated that CKMB activity was robust in the HFD mice. Interestingly, CKMB activity was normalized in the PB treated mice group. Free fatty acids (FFAs), and methylation levels were increased but the butyrate entity was decreased in the HFD mice group, suggesting ensuing of the “dysbiotic 1‐carbon metabolism” phenotype. Further, expression levels of PGC‐1α, and UCP1 were measured by Western blottings, and the MMP activity was estimated by zymography. The collagen histology was also performed on tissue samples collected from the mice. Contractions of isolated single myocytes were recorded employing an “Ion‐Optic” system, and the cardiac functions were scored by Echocardiography. The vasculature in the mice‐hearts was analyzed by BaSo4 X‐ray angiography, and the blood flow rate was studied using the Laser Doppler imaging system. Together, our findings suggest that mice fed with HFD gained significant weights, and they showed an increase in the systemic blood pressure, along with alterations of the vascular structures, and blood flow rates. Interestingly, some of the dysregulated effects were normalized by PB treatment. Furthermore, the extent of fibrosis, and MMP‐2 activity were quite robust in the HFD fed mice, and again the treatment with PB was able to mitigate cardiac tissue remodeling. Myocytes’ calcium‐dependent contractions were disrupted by consumption of the HFD, and treatment with PB was again able to mitigate the deleterious effects. We conclude that HFD induces dysbiosis of the “1‐carbon metabolism”, and treatment with PB creates eubiosis, and browning of the body fat.