Vitamin D Deficiency in Rats Causes Cardiac Dysfunction by Inducing Myocardial Insulin Resistance

• Published in: Molecular nutrition & food research Vol. 63; no. 17; pp. e1900109 - n/a
• Main Authors: Nizami, Hina Lateef, Katare, Parmeshwar, Prabhakar, Pankaj, Kumar, Yashwant, Arava, Sudheer Kumar, Chakraborty, Praloy, Maulik, Subir Kumar, Banerjee, Sanjay Kumar
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.09.2019
• Subjects: 25-Hydroxyvitamin D; Abnormalities; AKT protein; Animals; Blood pressure; blood serum; Calciferol; Calcitriol; cardiac remodeling; Cardiomegaly; Catalase; Cholesterol; Collagen; Congestive heart failure; Diet; Dyslipidemias - etiology; Echocardiography; Fetuses; Fibrosis; Fructose; Gene Expression Regulation; genes; Glucose; Glucose - metabolism; Glucose tolerance; glucose transporters; Heart; Heart - physiopathology; heart failure; High density lipoprotein; high density lipoprotein cholesterol; High fat diet; high fructose diet; Hyperinsulinism - etiology; Hypertension - etiology; Hypertrophy; Hypertrophy, Left Ventricular - etiology; Insulin; Insulin Resistance; interleukin-6; Male; males; messenger RNA; Metabolic disorders; Metabolic syndrome; Myocardium - metabolism; Nutrient deficiency; Palmitic acid; Phosphorylation; rats; Rats, Sprague-Dawley; Receptors, Calcitriol - genetics; Renin; Renin - genetics; Risk analysis; Risk factors; Superoxide dismutase; transcription factor NF-kappa B; transforming growth factor beta; Translocation; triacylglycerols; Triglycerides; tumor necrosis factor-alpha; Ventricular Remodeling; Vitamin D; vitamin D deficiency; Vitamin D Deficiency - complications; Vitamin D Deficiency - genetics; Vitamin D Deficiency - physiopathology; Vitamin deficiency; metabolic syndrome; heart failure; insulin resistance; vitamin D deficiency; cardiac remodeling
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201900109

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. 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.