Advances in biomedical applications of vitamin D for VDR targeted management of obesity and cancer
Vivek Kumar Gupta, Lipina Sahu, Sonam Sonwal, Achanti Suneetha, Dong Hyeon Kim, Jigyeong Kim, Henu Kumar Verma, Eluri Pavitra, Ganji Seeta Rama Raju, L.V.K.S. Bhaskar, Hyun Uk Lee, Yun Suk Huh
Abstract
1,25(OH) 2 D 3 is a fat-soluble vitamin, involved in regulating Ca 2+ 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) 2 D 3 blood level. In addition, 1,25(OH) 2 D 3 plays vital roles in Ca 2+ -P i and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes. The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH) 2 D 3 -deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery. Several studies have revealed that cancer development in a background of 1,25(OH) 2 D 3 deficient obesity involves the VDR gene. Moreover, 1,25(OH) 2 D 3 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) 2 D 3 -based therapies without any side effects. • Deficiencies of vitamin D and the VDR gene have been reported to be associated with obesity and obesity-related cancer. • VDR expression declines as the differentiation of adipose tissue progresses. • The adipogenesis suppressive effect of VDR may be due to its ability to cause competition between RXR and PPARγ. • Cancer can be cured with vitamin D supplementation. • Novel therapeutics may be developed along with the vitamin D supplement by targeting VDR, RXR, PPARγ, MARK and NF-kB signaling pathways.