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


RESULTS
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).


CONCLUSIONS
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).
Sanguino
E
E
Unidad de Farmacología y Farmacognosia, Facultad de Farmacia, Universidad de Barcelona. Avda Diagonal 643, 08028 Barcelona, Spain.
Bejarano
R
R
Alegret
M
M
Sánchez
R M
RM
Vázquez-Carrera
M
M
Laguna
J C
JC
D000217:Acyltransferases / Q000096:biosynthesis / Q000235:genetics; D000375:Aging / Q000378:metabolism*; D000818:Animals; D051048:Diacylglycerol O-Acyltransferase; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006728:Hormones / Q000097:blood; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D006728:Hormones; D047493:PPAR alpha; D000217:Acyltransferases; C494883:Dgat1 protein, rat; D051048:Diacylglycerol O-Acyltransferase