The influence of vitamin D on metabolic disease and adipose tissue metabolism

Abstract

Obesity is characterised as a chronic inflammatory state in which adipose tissue acts as a mediator of metabolic dysfunction leading to type 2 Diabetes Mellitus (T2DM). Several factors may influence this inflammatory state, with a considered influence due to arise through altered circulating levels of vitamin D (25(OH)D) which is known to be a common nutrient deficiency in obesity. Several studies to date have implicated low vitamin D (VitD) levels in association with the increased insulin resistance and T2DM, though the role of adipose tissue and its metabolism within adipose tissue remains unclear. As such, this thesis sought to investigate, (1) baseline VitD levels as a potential predictor of beneficial metabolic outcomes in participants undergoing bariatric surgery; (2) the in vitro association of VitD in different metabolic states and its influence on human adipocyte metabolism; (3) the influence of adiposity on VitD levels and metabolism. These investigations revealed several findings, specifically that (1) baseline VitD predicted 27% (p<0.001) of the presence of T2DM post-bariatric surgery and predicted 10% of weight regained at 18 months post-operatively (p=0.029); (2) the in vitro treatment with 10nM and 100nM VitD significantly downregulated inflammatory markers (P<0.05) and improved/restored glucose uptake in insulin resistant SGBS human adipocytes (21-37% rise respectively; P<0.05) through inhibition of mitogen-activated protein kinase (MAPK) and NFκβ pathways and stimulating GLUT4 translocation; and (3) VitD metabolic components (metabolizing enzymes and VDR) within AT are affected by adiposity and their expression levels are inversely associated with circulating VitD (p<0.05). In summary, these findings identify that VitD appears to reduce inflammation and restores glucose uptake in SGBS human adipocytes, and highlights the importance of VitD levels as an independent indicator for successful T2DM remission and weight loss, 12 months following sleeve gastrectomy (SG). Therefore, the use of baseline VitD levels may help us predict those more likely to achieve better health outcomes, as well as prioritize post-surgery support to achieve success for all participant groups. In addition, since VitD levels are associated with AT content of VitD hydroxylases, that are associated with body weight and fat mass, individuals with greater weight or fat mass may require higher doses of VitD to reach acceptable circulating levels