Impact of housing conditions on metabolic outcomes in high-fat diet-fed Mice

Spontaneous physical activity (SPA) represents a behavioral component contributing to energy dissipation and metabolic balance. However, it remains untested whether a cage-dimension-induced increase in SPA can mitigate the deleterious effects of high-fat diet-induced obesity in mouse models. This study aimed to evaluate metabolic outcomes in C57BL/6 mice housed in small (SC) or large cages (LC) and fed either AIN-93 M (control diet; CD) or a lard-enriched high-fat diet (HFD). Differential housing and diets began at 40 days of age (adolescent phase) and were maintained for 8 weeks. While animals in the SC groups had a floor space of 49.5 cm² per animal, those in the LC groups were provided with 267.9 cm² per animal, approximately five times larger. As expected, HFD feeding induced multiple detrimental effects compared with CD-fed mice; however, many of these effects were partially attenuated by LC housing. This is supported by the following findings: LCHFD mice, despite consuming a high-fat diet, exhibited increased recorded dark-phase SPA, reduced visceral fat accumulation (epididymal and retroperitoneal), lower fasting glucose levels, and higher muscle glycogen stores compared with SCHFD mice. Lower triglyceride stores in LCHFD mice also suggest that HFD-induced ectopic fat deposition may be attenuated by LC, although this effect appears to be muscle-specific, being evident in the quadriceps femoris but not in other muscles. Our findings provide an interesting translational insight suggesting that creating environments that encourage SPA may help attenuate metabolic impairments caused by a high-fat diet.