Low-vitamin-D diet lowers cerebral serotonin concentration in mature female mice

Low circulating 25-hydroxyvitamin D (25OHD) is commonly found in obese individuals and is often attributed to a volume dilution effect of adipose tissue. However, low vitamin D (LD) intake may contribute to the obesity itself. In this study, we examine whether low vitamin D status contributes to increased food intake and weight gain and can be explained by altered brain serotonin metabolism in 8-month-old female C57BL/6J mice. In a first experiment, mice were fed a 45% high-fat diet (HFD) containing different amounts of vitamin D at low (100 IU/kg), normal (1,000 IU/kg) or high (10,000 IU/kg) intake. After 10 weeks, mice fed LD had greater energy intake, weight gain, total and hepatic fat than the higher vitamin D groups (P < .05). In a second experiment, mice were examined for the central serotonin regulation of food intake after a 10% normal-fat diet (NFD) or 45% HFD containing low (100 IU/kg) or normal (1000 IU/kg) vitamin D. After 10 weeks, both HFD and LD diets attenuated circulating 25OHD concentration. Additionally, LD intake lowered cortical serotonin level, regardless of dietary fat intake (P < .05). In the arcuate and raphe nuclei, gene expression of vitamin D 1α-hydroxylase was lower due to LD during HFD feeding (P < .05). Tryptophan hydroxylase-2 and serotonin reuptake transporter gene expression was not altered due to LD. Overall, these findings suggest that a LD diet alters peripheral 25OHD, reduces central serotonin, and may contribute to weight gain in an obesogenic environment.