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

Nutr Res. 2020 Sep;81:71-80. doi: 10.1016/j.nutres.2020.07.006. Epub 2020 Jul 24.


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.

Keywords: high-fat diet; serotonin; tryptophan hydroxylase 2; vitamin D deficiency; vitamin D hydroxylase.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Body Composition
  • Brain / metabolism*
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cholestanetriol 26-Monooxygenase / metabolism
  • Diet, High-Fat
  • Dietary Fats / administration & dosage
  • Dorsal Raphe Nucleus / metabolism
  • Energy Intake
  • Female
  • Frontal Lobe / metabolism
  • Gene Expression
  • Gene Expression Regulation
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Serotonin / metabolism*
  • Vitamin D / administration & dosage*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamin D3 24-Hydroxylase / metabolism
  • Vitamins / administration & dosage*
  • Weight Gain


  • Dietary Fats
  • Vitamins
  • Vitamin D
  • Serotonin
  • 25-hydroxyvitamin D
  • Cholestanetriol 26-Monooxygenase
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase