Vitamin D Status and Vitamin D-Dependent Apoptosis in Obesity

Abstract

The role of vitamin D in obesity appears to be linked to vitamin D insufficient/deficient status. However, mechanistic understanding of the role of vitamin D in obesity is lacking. We have shown earlier that the vitamin D hormonal form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces cell death by apoptosis in mature adipocytes. This effect of the hormone is mediated by the cellular Ca2+ signaling pathway: a sustained increase of intracellular (cytosolic) Ca2+ concentration followed by activation of Ca2+-dependent initiators and effectors of apoptosis. In recent animal studies, we demonstrated that low vitamin D status is observed in diet-induced obesity (DIO). High intake of vitamin D3 in DIO decreased the weight of white adipose tissue and improved biomarkers related to adiposity and Ca2+ regulation. The anti-obesity effect of vitamin D (1,25(OH)2D3) in DIO was determined by the induction of Ca2+-mediated apoptosis in mature adipocytes executed by Ca2+-dependent apoptotic proteases (calpains and caspases). Thus, a high intake of vitamin D in obesity increases vitamin D nutritional status and normalizes vitamin D hormonal status that is accompanied by the reduction of adiposity. Overall, our findings imply that vitamin D may contribute to the prevention of obesity and obesity-related diseases and that the mechanism of the anti-obesity effect of 1,25(OH)2D3 includes induction of Ca2+-mediated apoptosis in adipocytes.

Potential Effects of a Modified Mediterranean Diet on Body Composition in Lipoedema

“…As fibers are involved in the modulation process of inflammation, immune system and microbiota equilibrium [ 22 ], fiber consumption from fruits and whole grains was significantly increased with respect to the baseline (LIPPY and CTRL: p < 0.0001). The mMeD content of molecules with antioxidant and anti-inflammatory activity [ 32 ] such as vitamins A (LIPPY and CTRL: p < 0.05), C (LIPPY: p < 0.0001, CTRL: p < 0.05), D (LIPPY and CTRL: p < 0.05) and minerals [ 40 , 41 , 42 ] was significant increased with respect to the baseline, with amelioration of the MAI index (LIPPY and CTRL: p < 0.0001).…”

The Molecular Mechanisms by Which Vitamin D Prevents Insulin Resistance and Associated Disorders

“…It is well documented that Ca 2+ is a key player in apoptosis and due to the vitamin D effect on the regulation of intracellular Ca 2+ level, it is suggested that the vitamin is involved in this process [ 206 , 207 , 208 ]. Sergeev et al have proposed a mechanism of intracellular Ca 2+ regulation and apoptosis by calcitriol in obesity.…”

“…Then, the activation of μ-calpain by the sustained cytosolic Ca 2+ signal was followed by the induction of Ca 2+ /calpain-dependent caspase-12. These activated proteases seem to be sufficient for the execution of apoptosis [ 207 ]. By contrast, Sun et al reported that calcitriol inhibited apoptosis and stimulated the expression of genes that promote the proliferation of human subcutaneous adipocytes [ 192 ].…”

Serum 25-hydroxyvitamin D level in relation to weight change and the risk of weight gain in adults of normal weight at baseline: the Norwegian HUNT cohort study

“…Emerging evidence suggests that vitamin D has a potential to improve insulin sensitivity that would reduce food intake. 30 In addition, in vitro and animal studies have shown that the bioactive form of vitamin D, 1,25-dihydroxyvitamin D can induce mature adipocytes death by apoptosis 32 ; in a high-fat diet-induced obesity mouse model, an increased intake of vitamin D is associated with a decreased weight of white adipose tissue due to induction of apoptosis.…”