title: The effect of dietary fish oil on weight gain and insulin sensitivity is dependent onAPOEgenotype in humanized targeted replacement mice.
abstract: We investigated the independent and interactive impact of the commonAPOEgenotype and marine n-3 polyunsaturated fatty acids (PUFAs) on the development of obesity and associated cardiometabolic dysfunction in a murine model. HumanAPOE3andAPOE4targeted replacement mice were fed either a control high-fat diet (HFD) or an HFD supplemented with 3% n-3 PUFAs from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, body weight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; andGlut4andApoEexpression in VAT. HFD feeding induced more weight gain and higher plasma lipids inAPOE3compared toAPOE4mice (P< 0.05), along with a 2-fold higher insulin and impaired glucose tolerance. SupplementingAPOE3, but notAPOE4,animals with dietary n-3 PUFAs decreased body-weight gain, plasma lipids, and insulin (P< 0.05) and improved glucose tolerance, which was associated with increased VATGlut4mRNA levels (P< 0.05). Our findings demonstrate that anAPOE3genotype 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 onAPOEgenotype in humanized targeted replacement mice.
authors.affiliation: Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Kenna E
authors.initials: KE
authors.lastname: Slim
authors.affiliation: Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Vauzour
authors.affiliation: Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Noemi
authors.initials: N
authors.lastname: Tejera
authors.affiliation: Department of Nutrition and Health, Louis Bolk Institute, Driebergen, The Netherlands; and.|Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.affiliation: Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Aedin
authors.initials: A
authors.lastname: Cassidy
authors.affiliation: Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; a.minihane@uea.ac.uk.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Minihane
mesh_terms: D000483:Alleles; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005395:Fish Oils / Q000494:pharmacology* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects; D008297:Male; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; D005395:Fish Oils
keywords: Glut4; IL-10; IPGTT; diabetes; glucose