Vitamin C protects against hypoxia, inflammation, and ER stress in primary human preadipocytes and adipocytes

Dysregulation of adipose tissue involves increased cellular hypoxia, ER stress, and inflammation and altered adipokine production, contributing to the aetiology of obesity-related diseases including type 2 diabetes and cardiovascular disease. This study aimed to investigate the effects of Vitamin C supplementation on these pro-cesses in primary human preadipocytes and adipocytes. Treatment of preadipocytes and adipocytes with the proinflammatory cytokine TNF alpha and palmitic acid (PA), to mimic the obesogenic milieu, significantly increased markers of hypoxia, ER stress and inflammation and reduced secretion of high molecular weight (HMW) adiponectin. Importantly, Vitamin C abolished TNF alpha+PA induced hypoxia and significantly reduced the increases in ER stress and inflammation in both cell types. Vitamin C also significantly increased the secretion of HMW adiponectin from adipocytes. These findings indicate that Vitamin C can reduce obesity-associated cellular stress and thus provide a rationale for future investigations.