Discovery - University of Dundee - Online Publications

Library & Learning Centre

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

Standard

A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. / McNeilly, A D; Williamson, R; Balfour, D J K; Stewart, C A; Sutherland, C (Lead / Corresponding author).

In: Diabetologia, Vol. 55, No. 11, 11.2012, p. 3061-3070.

Research output: Contribution to journalArticle

Harvard

McNeilly, AD, Williamson, R, Balfour, DJK, Stewart, CA & Sutherland, C 2012, 'A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin' Diabetologia, vol 55, no. 11, pp. 3061-3070.

APA

McNeilly, A. D., Williamson, R., Balfour, D. J. K., Stewart, C. A., & 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), 3061-3070doi: 10.1007/s00125-012-2686-y

Vancouver

McNeilly AD, Williamson R, Balfour DJK, Stewart CA, Sutherland C. A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. Diabetologia. 2012 Nov;55(11):3061-3070.

Author

McNeilly, A D; Williamson, R; Balfour, D J K; Stewart, C A; Sutherland, C (Lead / Corresponding author) / A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin.

In: Diabetologia, Vol. 55, No. 11, 11.2012, p. 3061-3070.

Research output: Contribution to journalArticle

Bibtex - Download

@article{2d4c10397b244934aafc7ae75506d401,
title = "A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin",
author = "McNeilly, {A D} and R Williamson and Balfour, {D J K} and Stewart, {C A} and C Sutherland",
year = "2012",
volume = "55",
number = "11",
pages = "3061--3070",
journal = "Diabetologia",
issn = "0012-186X",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin

A1 - McNeilly,A D

A1 - Williamson,R

A1 - Balfour,D J K

A1 - Stewart,C A

A1 - Sutherland,C

AU - McNeilly,A D

AU - Williamson,R

AU - Balfour,D J K

AU - Stewart,C A

AU - Sutherland,C

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

U2 - 10.1007/s00125-012-2686-y

DO - 10.1007/s00125-012-2686-y

M1 - Article

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 11

VL - 55

SP - 3061

EP - 3070

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy