Sexual dimorphism in lipid metabolic phenotype associated with old age in Sprague-Dawley rats

Aged male rats show a decrease in liver PPARalpha. We aimed to determine if the sexual dimorphism in lipid metabolism observed in the PPARalpha-/- mouse is also present in senescent rats.

Eighteen-month old rats were obese and presented high plasma NEFA concentrations. Old male rats were more hypercholesterolemic and hyperleptinemic than females, presenting a higher content in hepatic triglycerides and cholesteryl esters, while 18-month old females were more hypertriglyceridemic than males. Although PPARalpha expression and binding activity was reduced in liver from old male and female rats, the mRNA for a PPARalpha target gene, such as CPT-I, was reduced in old males (-56%), while increased by 286% in old females. LXRalpha protein was increased, and its binding activity was decreased in livers of old males, while livers of old females showed an increase in DGAT1 (2.6-fold) and DGAT2 (4.9-fold) mRNA, with respect to 3-month old animals. The increases in DGAT1 and DGAT2 mRNAs matched in old females those of plasma (3.1-fold) and liver triglycerides (5.0-fold).

These features disclose a marked sexual dimorphism in lipid metabolism associated to old age in rats that can be partially attributed not only to an age-related decrease in liver PPARalpha expression, but also to changes in other hepatic transcription factors and enzymes, such as liver X receptor alpha (LXRalpha) and diacylglycerol acyltransferases (DGAT).