Differences in triglyceride and cholesterol metabolism and resistance to obesity in male and female vitamin D receptor knockout mice

A lean phenotype has been detected in vitamin D receptor (VDR) knockout mice; however, the gender differences in fat metabolism between male and female mice both with age and in response to a high‐fat diet have not been studied before. The objective of our study was to assess changes in body and fat tissue weight, food intake and serum cholesterol and triglyceride in VDR knockout mice from weaning to adulthood and after a challenge of adult animals with a high‐fat diet. Although VDR knockout mice of both sexes consumed more food than wild‐type and heterozygous littermates, their body weight and the weight of fat depots was lower after 6 months on a diet with 5% crude fat content. When adult animals were challenged with a high‐fat diet containing 21% crude fat content for 8 weeks, VDR knockout mice of both sexes had a significantly higher food intake but gained less weight than their wild‐type littermates. Cholesterol levels were higher after 2 days on the high‐fat diet in both sexes, but in the VDR knockout mice, less cholesterol was detected in the serum after 8 weeks. Wild‐type male mice showed signs of fatty liver disease at the end of the experiment, which was not detected in the other groups. In conclusion, lack of the VDR receptor results in reduced fat accumulation with age and when adult mice are fed a high‐fat diet, despite a higher food intake of VDR knockout mice relative to their wild‐type littermates. These effects can be detected in both sexes. Wild‐type male mice react with the highest weight gain and cholesterol levels of all groups and develop fatty liver disease after 8 weeks on a high‐fat diet, while male VDR knockout mice appear to be protected.