Divergent Physical Activity and Novel Alternative Responses to High Fat Feeding in Polygenic Fat and Lean Mice

Abstract

We determined whether altered physical activity levels might underlie the contrasting adiposity of a divergently selected polygenic murine model of metabolic syndrome (Fat; F) and leanness (Lean; L) mice. We measured physical activity with a long term running wheel experiment and performed an additional high fat diet intervention. Further, we measured posture allocation by visual monitoring within the home cage as a non-exercise correlate of 'normal' physical activity. Whilst initially similar, running wheel activity of the F line declined with age, while the activity of the L line increased. Food intake was higher in the L line and increased with wheel exposure. Vertical rearing measured by video quantification in the home cage, without the stimulus of a running wheel was also significantly higher in the L line. The two lines developed novel alternate strategies to defend their body weight when exposed to high fat diets with a running wheel. F mice increased their running wheel activity, and despite unaltered food intake, still gained weight. L mice reduced their food intake and maintained activity levels without a significant change in body weight. Phenotypic selection for divergence in body fat content has co-segregated with a genetic predisposition for divergent physical activity levels and different strategies for coping with exposure to high fat diets that will facilitate the discovery of the genes underlying these important obesity related traits.

The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives

“…6) (Meek et al, 2010); unfortunately, home-cage activity was not measured. So far as we are aware, this stimulation of voluntary exercise by Western diet has not been previously reported in any rodent or human study [but see Simoncic et al (Simoncic et al, 2008) and discussion of that paper (Meek et al, 2010)]. In future studies, it will be important to determine the neural and/or metabolic mechanisms underlying this unique effect, as well as possible effects on NEAT/SPA and sedentary behaviours.…”

“…In mice, it has even been shown that certain diets can increase maximal sprint speed (C. Turbill and T. Ruf, personal communication) or stimulate voluntary exercise (Meek et al, 2010) and possibly SPA (Vaanholt et al, 2008) in a genotype-dependent fashion (Simoncic et al, 2008). Eating and physical activity are related not only through various biochemical and physiological pathways, but also via brain reward pathways and, it would seem, they may respond to environmental stimuli or evolve in non-intuitive ways.…”

“…When housed without wheel access, both the high capacity runner (HCR) and low capacity runner (LCR) lines of endurance-selected rats showed a similar decrease in daily activity levels in response to high-fat feeding for 1month (Novak et al, 2010). In a study of mice bred for low or high percent body fat, low-body-fat mice did not change their total wheel-running distance on being fed a high-fat diet (Simoncic et al, 2008). The high-body-fat mice fed a high-fat diet increased wheel running compared with high-body-fat mice fed regular chow, but running distances did not exceed values of low-body-fat animals on either diet (see fig.…”

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

“…However, studies examining voluntary activity in animals fed high-fat diet show a variety of responses. In a study using mice bred for low (L) or high (F) % body fat, Simoncic et al 28 reported that L% body fat mice did not change their total running distance on being fed high-fat diet. The F% body fat mice increased wheel running compared with F% body fat mice on regular chow, but running distances did not exceed values of L% body fat animals on either diet (Figure 3).…”

“…53,54 Both mice and human beings seem to exhibit 'compensatory mechanisms' to deal with excess caloric intake, including decreased food intake, increased metabolic rate and increased non-exercise activity thermogenesis 28,31,53,55,56 (but see the review by Westerterp 57 ). The increased wheel running by HR mice on WD (Figure 3) may represent an alternative compensatory mechanism.…”