A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin
Publication date
2012Keyword
Alzheimer DiseaseDrug therapy
Metabolism
Animals
Behavior
Drug effects
Physiology
Body weight
Brain
Cognition disorders
Conditioning
Operant
Dietary fats
Pharmacology
Disease models
Hormones
Blood
Hypoglycemic agents
Insulin resistance
Leptin
Male
Metformin
Nerve tissue proteins
Rats
Wistar
Signal transduction
Treatment failure
REF 2014
Open Access status
closedAccess
Metadata
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AIMS/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.Version
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McNeilly 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.Link to Version of Record
https://doi.org/10.1007/s00125-012-2686-yType
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1007/s00125-012-2686-y