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dc.contributor.authorMcNeilly, A.D.*
dc.contributor.authorWilliamson, Ritchie*
dc.contributor.authorBalfour, D.J.*
dc.contributor.authorStewart, C.A.*
dc.contributor.authorSutherland, C.*
dc.date.accessioned2014-04-28T10:58:34Z
dc.date.available2014-04-28T10:58:34Z
dc.date.issued2012
dc.identifier.citationMcNeilly AD, Williamson R, Balfour DJ, Stewart CA and Sutherland C (2012) A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. Diabetologia. 55(11): 3061-3070.
dc.identifier.urihttp://hdl.handle.net/10454/6095
dc.description.abstractAIMS/HYPOTHESIS: We previously demonstrated that animals fed a high-fat (HF) diet for 10 weeks developed insulin resistance and behavioural inflexibility. We hypothesised that intervention with metformin would diminish the HF-feeding-evoked cognitive deficit by improving insulin sensitivity. METHODS: Rats were trained in an operant-based matching and non-matching to position task (MTP/NMTP). Animals received an HF (45% of kJ as lard; n = 24), standard chow (SC; n = 16), HF + metformin (144 mg/kg in diet; n = 20) or SC + metformin (144 mg/kg in diet; n = 16) diet for 10 weeks before retesting. Body weight and plasma glucose, insulin and leptin were measured. Protein lysates from various brain areas were analysed for alterations in intracellular signalling or production of synaptic proteins. RESULTS: HF-fed animals developed insulin resistance and an impairment in switching task contingency from matching to non-matching paradigm. Metformin attenuated the insulin resistance and weight gain associated with HF feeding, but had no effect on performance in either MTP or NMTP tasks. No major alteration in proteins associated with insulin signalling or synaptic function was detected in response to HF diet in the hypothalamus, hippocampus, striatum or cortex. CONCLUSIONS/INTERPRETATION: Metformin prevented the metabolic but not cognitive alterations associated with HF feeding. The HF diet protocol did not change basal insulin signalling in the brain, suggesting that the brain did not develop insulin resistance. These findings indicate that HF diet has deleterious effects on neuronal function over and above those related to insulin resistance and suggest that weight loss may not be sufficient to reverse some damaging effects of poor diet.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1007/s00125-012-2686-y
dc.subjectAlzheimer Disease; Drug therapy; Metabolism
dc.subjectAnimals
dc.subject; Behavior; Drug effects; Physiology
dc.subject; Body weight
dc.subject; Brain
dc.subject; Cognition disorders
dc.subject; Conditioning; Operant
dc.subject; Dietary fats; Pharmacology
dc.subject; Disease models
dc.subject; Hormones; Blood
dc.subject; Hypoglycemic agents
dc.subject; Insulin resistance
dc.subject; Leptin
dc.subject; Male
dc.subject; Metformin
dc.subject; Nerve tissue proteins
dc.subject; Rats
dc.subject; Wistar
dc.subject; Signal transduction
dc.subject; Treatment failure
dc.subject; REF 2014
dc.titleA high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin
dc.typeArticle


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