Effects of overfeeding on energy balance and brown fat thermogenesis in obese (ob/ob) mice

Abstract

The genetically obese (ob/ob) mouse has been used extensively in experimental studies on obesity and to determine the mechanisms involved in regulating energy balance¹. Excess energy begins to accumulate in the ob/ob mouse from ∼12 days of age², but food intake during the suckling period and up to 4 weeks of age is no greater than in lean siblings^3–5. This indicates that the initial development of obesity in the ob/ob mutant is entirely due to a low energy expenditure, and this has been attributed to a reduction in thermoregulatory non-shivering thermogenesis^6–8, particularly that mediated by brown adipose tissue^9,10. Hyperphagia does, however, play an important part in the later development of obesity in ob/ob mice. Recent studies with young rats of the Sprague–Dawley strain fed a ‘cafeteria diet’ have suggested that an adaptive diet-induced thermogenesis, also mediated by brown adipose tissue, has a major role in minimizing the accumulation of energy during voluntary overfeeding^11–13. We now report the effects of overfeeding young lean and obese mice with a cafeteria-type diet, and show that while the lean animals retain little of their excess energy intake, most of the extra intake of the obese mice is deposited. This suggests that the capacity for diet-induced thermogenesis is reduced in the obese compared with the lean mice. We also show that the energy balance measurements are paralleled by different adaptive changes in brown adipose tissue in the two genotypes.