Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice

Abstract

Background Obesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart. Methods Seven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11 months after they had been on these diet regimens. Results HFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3 I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I. Conclusions These results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition.

Exercise Training Restores the Cardiac Microrna-16 Levels Preventing Microvascular Rarefaction in Obese Zucker Rats

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“…Pathological cardiac hypertrophy and dysfunction associated with metabolic disorders have been reported in obesity [4,5,6]. The obese Zucker rat (OZR), a genetic model of morbid obesity, presents many of the same cardiovascular deficits noted in obese humans including myocardial hypertrophy [5,7], cardiac microvascular rarefaction [8], and exercise intolerance [5,9].…”

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“…41,42 While Masson's trichrome staining of tissue sections from WT and KO mice showed increased collagen depositions in the hearts of all HFD-fed animals, male and female KO HFD mice showed a much greater area of fibrosis compared to WT HFD mice. In addition, male WT HFD and KO HFD mice had larger accumulation of fibrotic tissue compared to females within the same experimental group (Fig.…”

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“…Obesity is a prevalent risk factor for multiple disorders including insulin resistance, diabetes mellitus, some cancers (endometrial, breast and colon), and cardiovascular diseases (Cannon et al, 2016). Among the cardiovascular diseases, obesity-related cardiac hypertrophy (ORCH), cardiomyopathy, and even heart failure, were often reported (Wang et al, 2015, Zhang et al, 2015b. Previously, the majority of the research has focused on the effects of obesity on the adulthood's health, morbidity and mortality (Abdurrachim et al, 2014, Leopold, 2015 however, in recent years, childhood obesity has been demonstrated as a significant health issue.…”