Effect of selenium, ATM and DNA‐PKcs on adipocyte differentiation

Obesity and its complications are a worldwide health epidemic. Obesity contributes to and exacerbates many disease states. Although there have been attempts to treat obesity on a molecular level, obesity rates have continued to increase. It has also been shown that insulin‐stimulated glucose uptake by cells involve oxidative stress and ATM kinase activity, a PI(3)K family of serine/threonine kinase. We have found previously that the DNA damage response proteins ATM and DNA‐PK cs , another member of the PI(3)K family, are activated in response to oxidative stress in human normal fibroblasts. In this study, we hypothesize that ATM and DNA‐PK cs are important for adipocyte differentiation and that they could emerge as molecular targets for obesity intervention. We manipulated the standard adipocyte differentiation process of murine 3T3‐L1 preadipocytes and mouse embryonic fibroblasts with chemical inhibitors of ATM and DNA‐PK cs , as well as continuous exposure to pharmacological doses of insulin and selenium, a proposed insulin mimetic. We also tracked the phosphorylation patterns of ATM and DNA‐PK cs after the treatment. We found that selenium enhances differentiation while ATM and DNA‐PK cs inhibit adipocyte differentiation and that ATM and DNA‐PK cs are activated by treatment of differentiated adipocytes with selenium compounds. Take together, selenium interacts with ATM and DNA‐PK cs to modulate adipocyte differentiation. Grant Funding Source : NA