The Protective Effect of 1,25(OH)2D3 on Myocardial Function is Mediated via Sirtuin 3-Regulated Fatty Acid Metabolism

Yang, Jinghong; Zhang, Yalin; Pan, Yiming; Sun, Can Lan; Liu, Zuwang; Liu, Ning; Fu, Yu; Li, Xiaofeng; Li, Ye; Kong, Juan

doi:10.3389/fcell.2021.627135

Cited by 11 publications

(18 citation statements)

References 50 publications

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“…In this study, we did not observe changes in the expression of the most important cardiac transporters of FA, CD36 and FATP1. This nding is in line with the study of Yang et al [7], which also showed that the level of CD36 transporters in the heart does not change under the action of vitamin D in hyperlipidemic mice, con rming that it does not affect the transport of FA in the heart. CPT1, a marker of mitochondrial FA uptake, was also unchanged by vitamin D administration.…”

Section: Discussionsupporting

confidence: 91%

“…In addition, literature data have suggested that vitamin D plays a role in regulating energy metabolism [7]. Since maintaining a balance of energy metabolism is necessary to maintain normal heart function, vitamin D/VDR is thought to play a role in protecting cardiomyocytes by regulating the use of FA [7]. Considering all this, vitamin D seems to be a good candidate for additional therapy that would affect pathological changes in the diabetic heart.…”

Section: Introductionmentioning

confidence: 99%

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Cholecalciferol modulates fatty acid metabolism and calcium homeostasis in the heart

Ivković

Tepavčević

Romić

et al. 2022

Preprint

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Cholecalciferol modulates fatty acid metabolism and calcium homeostasis in the heart

Ivković

Tepavčević

Romić

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Another cardioprotective mechanism of vitamin D is the regulation of mitochondrial metabolism and energy supply [ 75 ].…”

Section: Vitamin D and Cardiomyocyte Remodelingmentioning

confidence: 99%

“…However, recent studies on exercise-induced remodeling in males and females show that female cardiac cells likely retain a lesser degree of metabolic flexibility to adaptation in stress or disease conditions [ 129 ]. Noticeably, in cardiac cells vitamin D is reported to impinge on the energy substrate balance, regulating fat uptake/fatty acid β-oxidation via sirtuin 3 [ 75 ].…”

Section: Vitamin D and Cardiomyocyte Remodelingmentioning

confidence: 99%

The Role of Estrogens and Vitamin D in Cardiomyocyte Protection: A Female Perspective

Crescioli

2021

Biomolecules

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Women experience a dramatical raise in cardiovascular events after menopause. The decline in estrogens is pointed to as the major responsible trigger for the increased risk of cardiovascular disease (CVD). Indeed, the menopausal transition associates with heart macro-remodeling, which results from a fine-tuned cell micro-remodeling. The remodeling of cardiomyocytes is a biomolecular response to several physiologic and pathologic stimuli, allowing healthy adaptation in normal conditions or maladaptation in an unfavorable environment, ending in organ architecture disarray. Estrogens largely impinge on cardiomyocyte remodeling, but they cannot fully explain the sex-dimorphism of CVD risk. Albeit cell remodeling and adaptation are under multifactorial regulation, vitamin D emerges to exert significant protective effects, controlling some intracellular paths, often shared with estrogen signaling. In post-menopause, the unfavorable association of hypoestrogenism-D hypovitaminosis may converge towards maladaptive remodeling and contribute to increased CVD risk. The aim of this review is to overview the role of estrogens and vitamin D in female cardiac health, speculating on their potential synergistic effect in cardiomyocyte remodeling, an issue that is not yet fully explored. Further learning the crosstalk between these two steroids in the biomolecular orchestration of cardiac cell fate during adaptation may help the translational approach to future cardioprotective strategies for women health.

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“…This is an unexpected finding that may indicate the presence of other compensatory mechanisms for regulation of metabolic flexibility in the heart. SIRT3 overexpression has been noted to rescue a range of cardiopathology phenotypes by improving the metabolic flexibility of cardiomyocytes (47,76). In this review, we summarize the molecular targets of SIRT3 involved in energy metabolism and elaborate on the underlying regulatory mechanisms observed in physiological and pathological cardiac metabolism.…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of SIRT3 in Cardiac Metabolism

Murugasamy

Munjal

Sundaresan

2022

Front. Cardiovasc. Med.

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The heart is a highly metabolically active organ that predominantly utilizes fatty acids as an energy substrate. The heart also derives some part of its energy by oxidation of other substrates, including glucose, lactose, amino acids and ketones. The critical feature of cardiac pathology is metabolic remodeling and loss of metabolic flexibility. Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins (SIRT1 to SIRT7), with NAD+ dependent deacetylase activity. SIRT3 is expressed in high levels in healthy hearts but downregulated in the aged or diseased hearts. Experimental evidence shows that increasing SIRT3 levels or activity can ameliorate several cardiac pathologies. The primary deacetylation targets of SIRT3 are mitochondrial proteins, most of which are involved in energy metabolism. Thus, SIRT3 improves cardiac health by modulating cardiac energetics. In this review, we discuss the essential role of SIRT3 in regulating cardiac metabolism in the context of physiology and pathology. Specifically, we summarize the recent advancements that emphasize the critical role of SIRT3 as a master regulator of cardiac metabolism. We also present a comprehensive view of all known activators of SIRT3, and elaborate on their therapeutic potential to ameliorate energetic abnormalities in various cardiac pathologies.

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The Protective Effect of 1,25(OH)2D3 on Myocardial Function is Mediated via Sirtuin 3-Regulated Fatty Acid Metabolism

Cited by 11 publications

References 50 publications

Cholecalciferol modulates fatty acid metabolism and calcium homeostasis in the heart

Cholecalciferol modulates fatty acid metabolism and calcium homeostasis in the heart

The Role of Estrogens and Vitamin D in Cardiomyocyte Protection: A Female Perspective

Emerging Roles of SIRT3 in Cardiac Metabolism

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