Cholecalciferol modulates fatty acid metabolism and calcium homeostasis in the heart

Abstract

Purpose Besides the traditional role in regulating calcium metabolism, vitamin D regulates energy metabolism and heart function. Based on the data that cholecalciferol improved insulin signaling and glucose metabolism in the heart and reduced circulating non-esterified fatty acids, we examined the effect of this vitamin on the metabolism of fatty acids in the heart and the consequences on calcium handling responsible for regulating myocardial contraction-relaxation. Methods Twelve-week-old rats (n = 10 per group) were treated with cholecalciferol for six weeks. Blood lipid profile was determined. Western blot and qRT-PCR were used to examine protein and mRNA expression. Results Cholecalciferol did not affect the expression of proteins involved in the transport of fatty acids in plasma membranes and mitochondria of heart cells, the expression of the β-oxidation enzyme, acyl-CoA dehydrogenase long chain, and the level of peroxisome proliferator-activated receptor alfa and Lipin1 in nuclear extract of heart cells. However, cholecalciferol-treated rats had increased acetyl CoA carboxylase 2 protein expression and decreased expression of malonyl CoA decarboxylase that regulates carnitine palmitoyltransferase–1 function via malonyl-coenzyme A. In addition, the expression of uncoupling protein 3 was elevated. Also, the level of peroxisome proliferator-activated receptor-gamma coactivator in the nucleus of heart cells was increased along with the level of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase in microsomal fraction. In parallel, the expression of L-type calcium channel and ryanodine receptor was reduced. Conclusion In the heart of healthy rats, cholecalciferol moderately attenuates fatty acid metabolism and fine-tunes calcium handling in terms of reducing calcium levels in the cytosol.

Cholecalciferol Effects on Lipid Profile of Experimental Animals: A Scoping Review

“…Similarly, Abeer and Suzan (2019), vitamin D3, also known as significantly improved plasma HDL-c in the gestational diabetes mellitus-induced rat group that injected IM with 20.000 IU/kg of vitamin D3. The mechanism of these actions is also observed in another study (Ivkovic et al, 2022). They found that cholecalciferol did not directly modify the nuclear content of βoxidation but improved β-oxidation by affecting the ACC/MCD expressions in malonyl-CoAmediated regulation of β-oxidation (Wang et al 2019).…”