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Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha.
Li, Guolin; Brocker, Chad N; Yan, Tingting; Xie, Cen; Krausz, Kristopher W; Xiang, Rong; Gonzalez, Frank J.
Afiliación
  • Li G; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Aging Biochemistry, College of Life Sciences, Hunan Normal University, Changsha 410081, China; The Key Laboratory of Protein Chemistry and Developmen
  • Brocker CN; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yan T; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Xie C; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Krausz KW; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Xiang R; The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha 41001, China.
  • Gonzalez FJ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gonzalef@mail.nih.gov.
Mol Metab ; 7: 80-89, 2018 01.
Article en En | MEDLINE | ID: mdl-29146411
BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. METHODS: Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen prior to acute fasting. Ppara-null mice were used to assess the contribution of PPARA activation during the metabolic response to EODF. Livers were collected for histological, biochemical, qRT-PCR, and Western blot analysis. RESULTS: Acute fasting activated PPARA and led to steatosis, whereas EODF protected against fasting-induced hepatic steatosis without affecting PPARA signaling. In contrast, pretreatment with Wy-14,643 did activate PPARA signaling but did not ameliorate acute fasting-induced steatosis and unexpectedly promoted liver injury. Ppara ablation exacerbated acute fasting-induced hypoglycemia, hepatic steatosis, and liver injury in mice, whereas these detrimental effects were absent in response to EODF, which promoted PPARA-independent fatty acid metabolism and normalized serum lipids. CONCLUSIONS: These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adaptación Fisiológica / Ayuno / PPAR alfa / Hígado Graso Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Mol Metab Año: 2018 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adaptación Fisiológica / Ayuno / PPAR alfa / Hígado Graso Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Mol Metab Año: 2018 Tipo del documento: Article Pais de publicación: Alemania