A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator- activated receptor alpha- deficient mice.
J Clin Invest
; 102(6): 1083-91, 1998 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-9739042
ABSTRACT
The peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor implicated in the control of cellular lipid utilization. To test the hypothesis that PPARalpha is activated as a component of the cellular lipid homeostatic response, the expression of PPARalpha target genes was characterized in response to a perturbation in cellular lipid oxidative flux caused by pharmacologic inhibition of mitochondrial fatty acid import. Inhibition of fatty acid oxidative flux caused a feedback induction of PPARalpha target genes encoding fatty acid oxidation enzymes in liver and heart. In mice lacking PPARalpha (PPARalpha-/-), inhibition of cellular fatty acid flux caused massive hepatic and cardiac lipid accumulation, hypoglycemia, and death in 100% of male, but only 25% of female PPARalpha-/- mice. The metabolic phenotype of male PPARalpha-/- mice was rescued by a 2-wk pretreatment with beta-estradiol. These results demonstrate a pivotal role for PPARalpha in lipid and glucose homeostasis in vivo and implicate estrogen signaling pathways in the regulation of cardiac and hepatic lipid metabolism.
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Transcription Factors
/
Carbohydrate Metabolism, Inborn Errors
/
Sex Factors
/
Receptors, Cytoplasmic and Nuclear
/
Feedback
/
Glucose
/
Lipid Metabolism, Inborn Errors
Aspects:
Determinantes_sociais_saude
Limits:
Animals
Language:
En
Journal:
J Clin Invest
Year:
1998
Document type:
Article