Weight loss normalizes plasma and adipose tissue vitamin D metabolism, and gene expression involved in the vitamin D metabolism in male mice with obesity.

Abstract

BACKGROUND: Obesity has consistently been linked to lower circulating total and free 25-hydroxyvitamin D (25(OH)D), and weight loss has been shown to enhance 25(OH)D levels in individuals with obesity. We examined whether weight loss would alter total and free 25(OH)D in a mouse model of diet-induced obesity, with controlled cholecalciferol intake. METHODS: Mice were fed either a low-fat (LF, n = 10) or a high-fat diet (HF, n = 20). After 7 weeks, half of the HF group transitioned to a low-fat diet (HF/LF) for 5 weeks, while the other mice maintained the same diet. RESULTS: The HF diet for 12 weeks increased body weight, adiposity, total 25(OH)D, and PTH plasma concentrations while reducing free 25(OH)D and cholecalciferol plasma levels. The LF-fed switch in mice resulted in a decrease in body weight. By the end of the experiment, HF/LF mice were comparable to LF animals in terms of total body weight, adiposity, and plasma PTH concentration. Interestingly, weight loss normalized most parameters related to vitamin D metabolism, including adipose tissue cholecalciferol and 25(OH)D content, as well as plasma total and free 25(OH)D; however, plasma cholecalciferol levels appeared reduced in the plasma of HF/LF mice compared to LF mice. The expression of genes related to vitamin D metabolism indicated that renal and adipose tissue uptake of protein-bound vitamin D was altered in HF/LF, which may partially explain the decrease in plasma cholecalciferol after weight loss. CONCLUSION: The data demonstrate the overall reversibility of the changes induced by diet-induced obesity in vitamin D metabolism; however, they also highlight that some parameters may be impacted chronically.