Investigations into the induction and effects of obesity in various murine models
There is at present much concern over the increased incidence of obesity in modern society. An increased energy intake and/or a decreased energy expenditure will lead to obesity. Murine models have been used to study the normal fat deposition during growth and excess fat deposition of obesity. Investigation of adipose depots during growth suggested that for the two strains of mice and the C57B1/6 ob/ob mice studied, the subcutaneous depot was the prominent fat store at weaning and that the proportion of fat in this depot decreased whilst that in the gonadal depot increased with age. Adult ob/ob mice had a large proportion of their fat stored subcutaneously although weight-reduction of male ob/ob mice resulted in a decrease in this depot size. Goldthioglucose and Bipiperidyl mustard have been used to induce obesity in mice. The results suggest this syndrome to be due to a metabolic defect since hyperphagia, hyperinsulinaemia and weight gains, the characteristic features of a regulatory defect were found to be diet-dependent and not essential for obesity-induction. It was demonstrated that the ventromedial hypothalamus regulated the total fat stores but not the fat content of each depot. The genetically-obese(ob/ob) syndrome was confirmed to be due to both hyperphagia and a reduced energy expenditure. These mice had a reduced feeding drive on fasting and they protected their excess fat stores(on fasting) by proteinolysis. Weight-reduction by meal-feeding did not decrease the proportion of fat as markedly in ob/ob mice as in chemically-obese mice. The weight-reduced ob/ob mice displayed a better cold tolerance(3°) than control ob/obs. The ob/ob mice had lower rectal temperatures at ambient temperature and, on fasting displayed a greater incidence of torpor and a slower rate of arousal than their lean littermates. Further, ob/ob mice exhibited torpor even when fed ad libitum. The experiments suggest that energy expenditure and control of lipid deposition is at least as important in the aetiology of obesity as regulation of energy intake.