Factors influencing individual variability in high fat diet-induced weight gain in out-bred MF1 mice

Easy access to high-energy palatable foods has been suggested to have contributed to the world-wide obesity epidemic. However, within these ‘obesogenic’ environments many people manage to remain lean. Mice also show variability in their weight gain responses to high-fat diet (HFD) feeding and their weight loss responses to calorically restricted (CR) feeding. In this study we investigated which factors contribute to determining susceptibility to HFD-induced obesity in mice, and whether the responses in weight gain on HFD are correlated with the responses to CR. One-hundred twenty four mice were exposed to 30% CR for 28days followed by a 14day recovery period, and subsequent exposure to 60% HFD for 28days. Responses in various metabolic factors were measured before and after each exposure (body mass; BM, body composition, food intake; FI, resting metabolic rate; RMR, physical activity, body temperature and glucose tolerance; GT).Weight changes on HFD ranged from −1 to 26%, equivalent to −0.2g to 10.5g in absolute mass. Multiple regression models showed that fat free mass (FFM) of the mice before exposure to HFD predicted 12% of the variability in weight gain on HFD (p<0.001). Also, FI during the first week of HFD feeding predicted 20% of the variability in BM and fat mass (FM) gain 4weeks later. These data may point to a role for the reward system in driving individual differences in FI and weight gain. Weight gain on the HFD was significantly negatively correlated to weight loss on CR, indicating that animals that are poor at defending against weight gain on HFD, were also poor at defending against CR-induced weight loss. Changes in FM and FFM in response to HFD or CR were not correlated however.