Factors Predicting Nongenetic Variability in Body Weight Gain Induced by a High‐Fat Diet in Inbred C57BL/6J Mice

Abstract

Inbred C57BL/6J mice displayed large individual variations in weight gain when fed a high‐fat diet (HFD). The objective of this study was to examine whether this predominantly nongenetic variability could be predicted by relevant baseline features and to explore whether variations in these significant features were influenced during pregnancy and/or lactation. Fat mass (FM), fat‐free mass (FFM), food intake (FI), resting metabolic rate (RMR), physical activity (PA), and body temperature (Tb) were all evaluated at baseline in 60 mice (aged 10–12 weeks) before HFD feeding. Regression analyses showed that baseline FM was a strong positive predictor of weight gain between 4 and 16 weeks of HFD. Baseline PA was negatively associated with weight gain at week 8, 12, and 16, and baseline FFM had a positive effect at week 12 and 16. In a second experiment, 40 female mice were mated and litter sizes (LS) were manipulated on day 3 of lactation. Weaning weight and postweaning growth rate (GR) had positive impacts on FM and FFM at age 9 weeks (FM, P = 0.001; FFM, P < 0.001: n = 97). Lactation LS had a negative effect on weaning weight and a positive effect on postweaning GR. In conclusion, our results show that obesity induced by HFD was associated with a higher baseline FM, a higher baseline FFM and a lower baseline PA level before the exposure of HFD. Two of these traits (FM and FFM) were influenced by lactation LS via weaning weight and postweaning GR.

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

“…Approximately 12% of the variation in BM and 11% of the variation in FM could be predicted by sex and FFM; animals that had a higher FFM before the diet intervention showed greater HFD-induced weight gain. These results agree with a previous study in inbred male C57BL/6 mice that found FFM to be a significant predictor of HFD-induced weight gain [55]. In that study, FM and physical activity were also shown to significantly contribute to the models, which is in agreement with a study using genetically obese ob/ob mice, which displayed reduced activity levels before the onset of obesity at the time when they were the same BM as their lean littermates [7].…”

“…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).…”

“…Baseline FI, fat mass (FM), fat free mass (FFM), RMR, general physical activity, Tb and GT were selected as potential predictors. These predictors were selected because previous studies have suggested that individual variability in the tendency to gain weight is associated with high FI, low RMR and low activity [36,44,54,55] and that there is an inverse relationship between Tb and obesity [29,38,45]. In addition to pre-existing variation in these traits, changes that occur in traits in response to high fat feeding may also contribute to the variability in HF diet-induced weight gain.…”

“…In addition, within these groups of animals (obesity resistant vs. obesity prone) individual variability in responses to HFD remains. Whether the extent to which individual variability prior to exposure of animals to HFD predisposes or protects individuals from weight gain has not been extensively studied in animal models (e.g., [3,28,55]). Zhang et al [55] showed that pre-existing differences in baseline physical activity levels, lean BM and body fatness were all predictors of weight gain in C57Bl/6 mice when exposed to a HFD, but that baseline FI, body temperature (Tb) and lean BM were not.…”

The evolution of body fatness: trading off disease and predation risk

“…As with studies on birds, the evidence with respect to stochastic variations in food supply are less clear cut compared with the impacts of modified predation risk. There is some limited support for the idea that increased stochasticity drives elevated fat storage Cao et al, 2009;Zhang et al, 2012;Zhu et al, 2014); however, other studies suggest the reverse (Monarca et al, 2015b). In humans, this idea is generally called the 'food insecurity' hypothesis, or the 'hunger-obesity' paradigm (Nettle et al, 2017;Dhurandhar, 2016), i.e.…”