Factors influencing individual variability in high fat diet-induced weight gain in out-bred MF1 mice L.M. Vaanholt a, ⁎, R.E. Sinclair a , S.E. Mitchell a , J.R. Speakman a,b a Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK b Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China HIGHLIGHTS • Individual variability in high fat diet-induced weight loss was studied in MF1 mice. • Pre-existing differences and changes in compensation were investigated. • Fat free mass and sex predicted around 12% of the variability in body mass. • Food intake during the 1st week of high fat feeding predicted 20% of the variability. • Mice that gained more weight on high fat diet lost more when dietary restricted. abstract article info Article history: Received 15 December 2014 Received in revised form 13 March 2015 Accepted 22 March 2015 Available online 24 March 2015 Keywords: Obesity Physical Activity Energy expenditure Glucose Food preference Easy access to high-energy palatable foods has been suggested to have contributed to the world-wide obesity ep- idemic. 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 suscep- tibility 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 28 days followed by a 14 day recov- ery period, and subsequent exposure to 60% HFD for 28 days. 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 -0.2 g to 10.5 g in absolute mass. Multiple regres- sion 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 b 0.001). Also, FI during the first week of HFD feeding predicted 20% of the variability in BM and fat mass (FM) gain 4 weeks later. These data may point to a role for the reward system in driving indi- vidual 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. © 2015 Elsevier Inc. All rights reserved. 1. Introduction The ‘obesogenic’ environment of modern society, with its high abun- dance of palatable energy-dense foods, has led to a gradual increase in the number of people that suffer from obesity and related diseases [12,23]. However, the response amongst people exposed to such ‘obesogenic’ environments is highly variable; some people are suscepti- ble to weight gain while others remain lean [3]. Studying this individual variability in responses could reveal processes of individual weight regulation and establish the biological factors that make people either susceptible or resistant to weight gain, which is crucial to increase our understanding of the aetiology of obesity. For example, in male Sprague Dawley rats on pure macronutrient or high fat diets, measures of weight gain, energy intake or fat preference are shown to vary considerably in direct proportion to ultimate body fat gain ([28,39,49], also see [55] in mice). Substantial individual variability in weight loss is also observed in response to caloric restriction (CR) (e.g., humans [1,5], mice [47]). For instance, weight loss ranged from 1 to 36% in mice that had exposed to 30% CR for 4 weeks [47]. In this previous study, ~70% of the variation Physiology & Behavior 144 (2015) 146–155 ⁎ Corresponding author at: Institute of Biological and Environmental Sciences, University of Aberdeen, Zoology Building, Aberdeen AB24 2TZ, UK. E-mail address: l.vaanholt@abdn.ac.uk (L.M. Vaanholt). http://dx.doi.org/10.1016/j.physbeh.2015.03.029 0031-9384/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/phb