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dc.contributor.authorBaranowski, Bradley J
dc.contributor.authorBott, Kirsten N.
dc.contributor.authorMacPherson, Rebecca E. K.
dc.date.accessioned2019-07-16T17:18:17Z
dc.date.available2019-07-16T17:18:17Z
dc.date.issued2018-05-15
dc.identifier.citationPhysiol Rep, 6 (11), 2018, e13729en_US
dc.identifier.issn2051-817X
dc.identifier.urihttp://hdl.handle.net/10464/14279
dc.description.abstractMetabolic dysfunction related to diet-induced obesity has recently been linked to the pathogenesis of sporadic Alzheimer’s disease (AD). However, the underlying mechanisms linking obesity and AD remain unclear. The purpose of this study was to examine early alterations in brain insulin signaling, inflammatory/stress markers, and energetic stress in a model of diet-induced obesity during middle age. Male C57BL/6J mice were randomized to either a control diet (AGE n = 12) or high-fat and sucrose diet (AGE-HFS n = 12) for 13-weeks from 20-weeks of age. Prefrontal cortex and hippocampal samples were collected at 20-weeks of age (BSL n = 11) and at 33-weeks of age (AGE and AGE-HFS). The HFS diet resulted in increased body weight (30%; P = 0.0001), increased %fat mass (28%; P = 0.0001), and decreased %lean mass (33%; P = 0.0001) compared to aged controls. In the prefrontal cortex, AGE-HFS resulted in increased 50 adenosine monophosphate – activated protein kinase (AMPK) phosphorylation (P = 0.045). In the hippocampus, AGEHFS resulted in increased extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation and protein kinase B (Akt) serine473 and glycogen synthase kinase (GSK) phosphorylation (P < 0.05). Results from this study demonstrate that aging combined with a HFS diet results in increased inflammation (pERK and pJNK) and energetic stress (pAMPK) in the hippocampus and prefrontal cortex, respectively. Together these novel results provide important information for future targets in early AD pathogenesis.en_US
dc.description.sponsorshipBrock University Library Open Access Publishing Funden_US
dc.language.isoenen_US
dc.publisherAmerican Physiological Societyen_US
dc.subjectAgingen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectinflammationen_US
dc.subjectinsulin resistanceen_US
dc.subjectobesityen_US
dc.titleEvaluation of neuropathological effects of a high-fat high-sucrose diet in middle-aged male C57BL6/J miceen_US
dc.typeArticleen_US
dc.identifier.doi10.14814/phy2.13729


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