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

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. 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. 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. 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.