Vitamin D Deficiency in Rats Causes Cardiac Dysfunction by Inducing Myocardial Insulin Resistance. Issue 17 (5th June 2019) - Nizami, Hina Lateef
Abstract : Scope: Cause‐effect relationship between vitamin D deficiency and cardiometabolic abnormalities remains undefined. The aim is to investigate the role of vitamin D deficiency in cardiac failure, through possible involvement in myocardial insulin signaling. Methods and results: Male SD rats ( n = 6) are fed a normal diet (Con), vitamin D‐deficient diet [Con(‐)], or high‐fat, high fructose diet (HFHFrD) for 20 weeks. Cardiac hypertrophy and fetal gene program are confirmed in Con(‐) group. Cardiac dysfunction is assessed by echocardiography. Elevated renin, TGF‐β and collagen‐1α mRNAs, p‐ERK1/2, and perivascular fibrosis indicate cardiac remodeling in Con(‐) group. Increased serum insulin, triglycerides, and blood pressure, and decreased glucose tolerance and HDL cholesterol are observed in Con(‐) rats. Decreased p‐Akt/Akt, GLUT4, SOD2, and catalase, and increased NF‐κB, TNF‐α, and IL‐6 are observed in Con(‐) hearts. In H9c2 cells, calcitriol attenuates palmitate‐induced insulin resistance. VDR‐silenced H9c2 cells show reduced Akt phosphorylation, GLUT4 translocation, and 2‐NBDG uptake. Findings in Con(‐) and HFHFrD groups are comparable. Conclusion: Vitamin D deficiency in rats mimic high‐fat‐, high‐fructose‐induced metabolic syndrome and cardiac dysfunction. This study demonstrates that vitamin D deficiency is an independent risk factor for heart failure, at least in part, through induction of myocardial insulin resistance. Abstract : Vitamin D deficiency causes adverse cardiac outcomes, such as hypertrophy and fetal gene program. Insulin resistance due to vitamin D deficiency further impairs cardiac function. The hypertrophic adaptive response does not suffice to preserve cardiac function, and the heart progresses to failure. We propose that myocardial insulin resistance is, in part, responsible for cardiac failure caused by vitamin D deficiency.