| Hypothalamic JNK1 and IKKβ Activation and Impaired Early Postnatal Glucose Metabolism after Maternal Perinatal High-Fat Feeding. | |
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MedLine Citation:
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PMID: 22147015 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Hypothalamic inflammation has been demonstrated to be an important mechanism in the pathogenesis of obesity-induced type 2 diabetes mellitus. Feeding pregnant and lactating rodents a diet rich in saturated fatty acids has consistently been shown to predispose the offspring for the development of obesity and impaired glucose metabolism. However, hypothalamic inflammation in the offspring has not been addressed as a potential underlying mechanism. In this study, virgin female C57BL/6 mice received high-fat feeding starting at conception until weaning of the offspring at postnatal d 21. The offspring developed increased body weight, body fat content, and serum leptin concentrations during the nursing period. Analysis of hypothalamic tissue of the offspring at postnatal d 21 showed up-regulation of several members of the toll-like receptor 4 signaling cascade and subsequent activation of c-Jun N-terminal kinase 1 and IκB kinase-β inflammatory pathways. Interestingly, glucose tolerance testing in the offspring revealed signs of impaired glucose tolerance along with increased hepatic expression of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. In addition, significantly increased hepatic and pancreatic PGC1α expression suggests a role for sympathetic innervation in mediating the effects of hypothalamic inflammation to the periphery. Taken together, our data indicate an important role for hypothalamic inflammation in the early pathogenesis of glucose intolerance after maternal perinatal high-fat feeding. |
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Authors:
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Eva Rother; Ruth Kuschewski; Miguel Angel Alejandre Alcazar; André Oberthuer; Inga Bae-Gartz; Christina Vohlen; Bernhard Roth; Jörg Dötsch |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-6 |
Journal Detail:
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Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pediatrics, University Hospital of Cologne, 50924 Cologne, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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