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Titolo:
Peroxisome proliferator-activated receptor-alpha regulates lipid homeostasis, but is not associated with obesity - Studies with congenic mouse lines
Autore:
Akiyama, TE; Nicol, CJ; Fievet, C; Staels, B; Ward, JM; Auwerx, J; Lee, SST; Gonzalez, FJ; Peters, JM;
Indirizzi:
Penn State Univ, Dept Vet Sci, Ctr Mol Toxicol, University Pk, PA 16802 USA Penn State Univ University Pk PA USA 16802 l, University Pk, PA 16802 USA NCI, Met Lab, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892NCI, Met Lab, NIH, Bethesda, MD 20892 USA Inst Pasteur, INSERM, Dept Atherosclerose, F-59019 Lille, France Inst Pasteur Lille France F-59019 Atherosclerose, F-59019 Lille, France NCI, Vet & Tumour Pathol Sect, Off Lab Anim Resources, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA NCI Ft Detrick MD USA 21702 Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67400 Illkirch Graffenstaden, France Univ Strasbourg 1 Illkirch Graffenstaden France F-67400 enstaden, France Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China Chinese Univ Hong Kong Shatin Hong Kong Peoples R China Peoples R China
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 42, volume: 276, anno: 2001,
pagine: 39088 - 39093
SICI:
0021-9258(20011019)276:42<39088:PPRRLH>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
FATTY-ACID OXIDATION; PPAR-ALPHA; GENE-EXPRESSION; DEFICIENT MICE; TARGETED DISRUPTION; ADAPTIVE RESPONSE; TRANSGENIC MICE; BILE-ACID; NULL MICE; KAPPA-B;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Peters, JM Penn State Univ, Dept Vet Sci, Ctr Mol Toxicol, 226 Fenske Lab,UniversityPk, PA 16802 USA Penn State Univ 226 Fenske Lab University Pk PAUSA 16802 2 USA
Citazione:
T.E. Akiyama et al., "Peroxisome proliferator-activated receptor-alpha regulates lipid homeostasis, but is not associated with obesity - Studies with congenic mouse lines", J BIOL CHEM, 276(42), 2001, pp. 39088-39093

Abstract

Considerable controversy exists in determining the role of peroxisome proliferator-activated receptor-a (PPAR alpha) in obesity. Two purebred congenic strains of PPAR alpha -null mice were developed to study the role of thisreceptor in modulating lipid transport and storage. Weight gain and average body weight in wild-type and PPAR alpha -null mice on either an Sv/129 ora C57BL/6N background were not markedly different between genotypes from 3to 9 months of age. However, gonadal adipose stores were significantly greater in both strains of male and female PPAR alpha -null mice. Hepatic accumulation of lipids was greater in both strains and sexes of PPAR alpha -null mice compared with wild-type controls. Administration of the peroxisome proliferator WY-14643 caused hepatomegaly, alterations in mRNAs encoding proteins that regulate lipid metabolism, and reduced serum triglycerides in a PPAR alpha -dependent mechanism. Constitutive differences in serum cholesterol and triglycerides in PPAR alpha -null mice were found between genetic backgrounds. Results from this work establish that PPAR alpha is a critical modulator of lipid homeostasis in two congenic mouse lines. This study demonstrates that disruption of the murine gene encoding PPAR alpha results in significant alterations in constitutive serum, hepatic, and adipose tissue lipid metabolism. However, an overt, obese phenotype in either of the two congenic strains was not observed. In contrast to earlier published work, this study establishes that PPAR alpha is not associated with obesity in mice.

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Documento generato il 09/07/20 alle ore 01:34:10