Choline metabolism is sexual dimorphic in the mouse

Abstract

Premenopausal women are relatively resistant to choline deficiency compared with postmenopausal women and men. Moreover, studies in animals and human hepatocytes suggest that phosphatidylethanolamine N‐methyltransferase (PEMT) is regulated by estrogen. In this study we investigated whether choline metabolism is sexual dimorphic using a choline dehydrogenase (CHDH) knockout mouse model. After weaning, wild‐type (WT) and knockout (KO) mice were fed AIN‐76A diet for 4 weeks, and livers were collected. Hepatic choline and metabolites concentrations were measured using LC/MS. As expected, CHDH KO animals had significantly lower betaine and higher choline and phosphocholine concentrations than did WT animals, p<0.001. WT females had lower hepatic choline and phosphocholine concentrations, but higher glycerophosphocholine concentrations than WT males. When we knocked out CHDH, the gender differences in hepatic choline and phosphocholine concentrations disappeared, suggesting that CHDH activity plays a role in sexual dimorphism in choline metabolism. We also found that males did not differ in hepatic triacylglycerol regardless of genotype, but female KO mice had 2‐fold more liver fat than did males, p<0.05. We are currently studying whether the expression of CHDH is estrogen responsive.Teng and Johnson contributed equally to this work.