Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis

Autor: Thierry Pineau, Philippe Costet, Jean More, Alan Edgar, Pierre Galtier, Christiane Legendre
Přispěvatelé: Unité de recherche Pharmacologie-Toxicologie (UPT), Institut National de la Recherche Agronomique (INRA), Laboratoires Fournier SCA, Partenaires INRAE
Jazyk: angličtina
Rok vydání: 1998
Předmět:
Male
Adipose tissue
Peroxisome proliferator-activated receptor
Receptors
Cytoplasmic and Nuclear
Fibrate
Biochemistry
PHARMACOLOGIE
HISTOLOGIE
SANTE
ADIPOGENESE
Mice
chemistry.chemical_classification
Mice
Knockout
Sex Characteristics
acide gras
Fatty liver
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biomolecules [q-bio.BM]
obésité
Female
Peroxisome proliferator-activated receptor alpha
transcription
récepteur
medicine.medical_specialty
medicine.drug_class
Hyperlipidemias
Biology
poids corporel
Internal medicine
medicine
Animals
triglyceride
Obesity
Molecular Biology
métabolisme
lipide
Lipid metabolism
Cell Biology
peroxysome
medicine.disease
dimorphisme sexuel
Fatty Liver
Mice
Inbred C57BL
Endocrinology
chemistry
Nuclear receptor
teneur en lipides
technique analytique
Steatosis
Transcription Factors
Zdroj: Journal of Biological Chemistry
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1998, 273 (45), pp.29577-29585. ⟨10.1074/jbc.273.45.29577⟩
Journal of Biological Chemistry 45 (273), 29577-29585. (1998)
ISSN: 0021-9258
1083-351X
DOI: 10.1074/jbc.273.45.29577⟩
Popis: The alpha-isoform of the peroxisome proliferator-activated receptor (PPARalpha) is a nuclear transcription factor activated by structurally diverse chemicals referred to as peroxisome proliferators. Activators can be endogenous molecules (fatty acids/steroids) or xenobiotics (fibrate lipid-lowering drugs). Upon pharmacological activation, PPARalpha modulates target genes encoding lipid metabolism enzymes, lipid transporters, or apolipoproteins, suggesting a role in lipid homeostasis. Transgenic mice deficient in PPARalpha were shown to lack hepatic peroxisomal proliferation and have an impaired expression and induction of several hepatic target genes. Young adult males show hypercholesterolemia but normal triglycerides. Using a long term experimental set up, we identified these mice as a model of monogenic, spontaneous, late onset obesity with stable caloric intake and a marked sexual dimorphism. Serum triglycerides, elevated in aged animals, are higher in females that develop a more pronounced obesity than males. The latter show a marked and original centrilobular-restricted steatosis and a delayed occurrence of obesity. Fat cells from their liver express substantial levels of PPARgamma2 transcripts when compared with lean cells. These studies demonstrate, in rodents, the involvement of PPARalpha nuclear receptor in lipid homeostasis, with a sexually dimorphic control of circulating lipids, fat storage, and obesity. Characterization of this pathological link may help to delineate new molecular targets for therapeutic intervention and could lead to new insights into the etiology and heritability of mammalian obesity.
Databáze: OpenAIRE
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