Locus-specific epigenetic changes associated with peripheral leptin resistance in increased resistance to a high-fat diet in mice born to obese mothers fed a control diet during gestation

Autor: Attig, Linda, Jais, J.P., Vigé, A., Beauger, Aurore, Gross, M.S., Gallou-Kabani, C., Gothié, J.D., Gabory, Anne, Jouneau, Luc, Junien, Claudine
Přispěvatelé: Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], U781, Institut National de la Santé et de la Recherche Médicale, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA) - AgroParisTech, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Société Francophone pour la Recherche et l'Education sur les Origines Développementales, Environnementales et Epigénétiques de la Santé et des Maladies (SF-DOHAD). FRA., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Founding meeting of SF-DOHaD
Colloque SF-DOHaD
Colloque SF-DOHaD, Nov 2012, Paris, France. Cambridge University Press, 4 (Supplement 1), pp.S42, 2013, Journal of Developmental Origins of Health and Disease. 〈10.1017/S2040174412000797〉
Founding meeting of SF-DOHaD. (4 (Supplement 1))2013; Colloque SF-DOHaD, Paris, FRA, 2012-11-08-2012-11-09, S42
Journal of Developmental Origins of Health and Disease
Colloque SF-DOHaD, Société Francophone pour la Recherche et l'Education sur les Origines Développementales, Environnementales et Epigénétiques de la Santé et des Maladies (SF-DOHAD). FRA., Nov 2012, Paris, France. pp.S42, ⟨10.1017/S2040174412000797⟩
Colloque SF-DOHaD, Nov 2012, Paris, France. pp.S42, ⟨10.1017/S2040174412000797⟩
DOI: 10.1017/S2040174412000797〉
Popis: Epigenetic mechanisms are evoked to explain interindividual and across-generation variations in the proneness or resistance to develop diet-induced obesity (DIO) of inbred C57BL/6J mice even under the same high-fat diet.1,2 Feeding obese and diabetic mothers a control diet during the periconceptional/gestation/ lactation period led to a pronounced sex-specific shift from proneness to resistance to DIO in the offspring.3 In this study, Affymetrix microarrays highlighted the prominent role of leptin–leptin receptor cytokine pathways and a cross-talk between muscle and liver. The top-ranking genes were the leptin (Lep) gene upregulated in muscle, and the leptin receptor (Lepr) and suppressor of cytokine signaling 2 (Socs2) genes drastically downregulated in liver only. Weight-gain proneness as opposed to resistance was associated in muscle with an inflammatory process related to altered levels of adipokines, and in liver with an altered lipid processing and increased lipid droplets formation, suggesting a strong connection of Lepr and Socs2 to fat metabolism. Locus-specific epigenetic analyses by bisulfite-pyrosequencing and ChIP PCR of Lep, Lepr and Socs2 revealed a role for specific CpG methylation and histone acetylation and methylation marks in the tissue-specific regulation of these genes with specific profiles associated with the obesity-prone phenotype, whereas resistant mice epigenetic landscapes evoked a strong tendency toward ‘normality’. Emphasizing the hitherto unsuspected role of Lepr gene expression in peripheral leptin resistance4 and its liver specificity, this work is the first to describe epigenetic changes in Lepr associated with its downregulation as potentially useful markers in the follow-up of leptin resistance treatment in obese patients.
Databáze: OpenAIRE
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