Advances in biomedical applications of vitamin D for VDR targeted management of obesity and cancer

Background: 1,25(OH)₂D₃ is a fat-soluble vitamin, involved in regulating Ca²⁺ homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is the result of abnormal lipid deposition due to the prolonged positive energy balance and increases the risk of several cancer types. Furthermore, it has been associated with vitamin D deficiency and defined as a low 25(OH)₂D₃ blood level. In addition, 1,25(OH)₂D₃ plays vital roles in Ca²⁺-P_i and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes. Scope and approach: The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH)₂D₃-deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery. Key findings and conclusions: Several studies have revealed that cancer development in a background of 1,25(OH)₂D₃ deficient obesity involves the VDR gene. Moreover, 1,25(OH)₂D₃ is also known to influence several cellular processes, including differentiation, proliferation, and adhesion. The multifaceted physiology of obesity has improved our understanding of the cancer therapeutic targets. However, currently available anti-cancer drugs are notorious for their side effects, which have raised safety issues. Thus, there is interest in developing 1,25(OH)₂D₃-based therapies without any side effects.