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

We investigated the independent and interactive impact of the common genotype and marine n-3 polyunsaturated fatty acids (PUFAs) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human and targeted 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; and and expression in VAT. HFD feeding induced more weight gain and higher plasma lipids in compared to mice ( < 0.05), along with a 2-fold higher insulin and impaired glucose tolerance. Supplementing , but not animals with dietary n-3 PUFAs decreased body-weight gain, plasma lipids, and insulin ( < 0.05) and improved glucose tolerance, which was associated with increased VAT mRNA levels ( < 0.05). Our findings demonstrate that an 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 genotype in humanized targeted replacement mice.