Vitamin D Status and Vitamin D-Dependent Apoptosis in Obesity

• Main Author: Igor N. Sergeev
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Nutrients
• Subjects: 1,25-dihydroxyvitamin D₃; apoptosis; adipocytes; intracellular Ca²⁺; obesity; vitamin D status
• Online Access: https://www.mdpi.com/2072-6643/12/5/1392

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.