The development of obesity in animals: the role of genetic susceptibility

Abstract

There are a number of animals in which obesity is genetically determined. In some the inheritance is polygenic while in others it is by a single-gene mutation. In the most widely studied single-gene mutants--the obese (ob/ob) mouse, the diabetic-obese (db/db) mouse and the Zucker (fa/fa) rat-obesity is very substantial and is initiated before the animals are weaned. Although hyperphagia is a feature of all the major obese mutants, it is not a prerequisite for the development of obesity. The initiation of the disorder during the suckling period takes place on a normal energy intake, and excess rates of energy deposition will still continue after weaning if the obese mutants are pair-fed to the ad libitum energy intake of lean siblings. The ability to become obese without hyperphagia indicates that one or more components of energy expenditure must be reduced in the obese mutants. Studies on the ob/ob mouse have demonstrated that a reduction in thermogenesis in BAT is the main way by which this is achieved. The reduction in energy expenditure in BAT is due primarily to a low activity of the sympathetic innervation to the tissue. Once hyperphagia is established, apparently as a secondary feature of the obese syndrome, the development of obesity is accelerated, the obese mutants having an impairment in the dietary stimulation of BAT thermogenesis. Studies on different types of obese animal suggest that an inability to respond to dietary stimuli is a general feature of obesity. The final syndrome presented by genetically obese animals is of considerable metabolic and endocrinological complexity. However, it is now possible to begin to integrate some of the endocrinological abnormalities within the energy balance framework, centred on BAT, that has been developed over the past few years. This is particularly evident in the case of adrenal function in the Zucker rat; adrenalectomy of this mutant has important effects on energy balance and in the normalization of the thermogenic activity of BAT. The sensitivity of BAT to insulin is also emerging as a possible factor of importance in the modulation of thermogenesis in obese animals.(ABSTRACT TRUNCATED AT 400 WORDS)