The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice

Slim, Kenna E., Vauzour, David, Tejera, Noemi, Voshol, Peter J., Cassidy, Aedin and Minihane, Anne Marie (2017) The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice. The FASEB Journal, 31 (3). pp. 989-997. ISSN 0892-6638

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Abstract

We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFA) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a high-fat control diet (HFD) or a HFD supplemented with 3% n-3 PUFA from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, bodyweight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; and Glut4 and ApoE expression in VAT. HFD feeding induced more weight gain and higher plasma lipids in APOE3 compared to APOE4 mice (P < 0.05), along with a 2-fold higher insulin and impaired glucose tolerance. Supplementing APOE3, but not APOE4, animals with dietary n-3 PUFA decreased bodyweight gain, plasma lipids, and insulin (P < 0.05) and improved glucose tolerance, which was associated with increased VAT Glut4 mRNA levels (P < 0.05). Our findings demonstrate that an APOE3 genotype predisposes mice to develop obesity and its metabolic complications, which was attenuated by n-3 PUFA supplementation.—Slim, K. E., Vauzour, D., Tejera, N., Voshol, P. J., Cassidy, A., Minihane, A. M. The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice.

Item Type: Article
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) (http://creativecommons.org/licenses/by-nc/4.0/) which permits noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: diabetes,glucose,glut4,il-10,ipgtt
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 01 Dec 2016 00:03
Last Modified: 22 Apr 2020 01:57
URI: https://ueaeprints.uea.ac.uk/id/eprint/61549
DOI: 10.1096/fj.201600921RR

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