Brown fat thermogenesis and body weight regulation in mice: relevance to humans.

Physiological, pharmacological and genetic studies in dogs, mice and rats have established that the uncoupling protein-1 (UCP1)-based brown adipose tissue system has an important role in the regulation of body temperature. Although it may be possible to create laboratory conditions in which mice with inactivated Ucp1 can survive in a modestly cooled environment, data overwhelmingly support the conclusion that the UCP1/BAT system has evolved to maintain body temperature at 37 °C. The corollary to this conclusion is that any influence UCP1/BAT might have on body weight regulation is a secondary function. The idea that BAT prevents obesity by burning off excess energy to maintain energy balance seems incompatible with evolutionary biology. Premodern humans spent an enormous amount of energy either running to catch their meal or avoiding becoming a meal themselves; consequently, there was no obesity. Nevertheless, although secondary to body temperature regulation, UCP1/BAT is extraordinarily effective at reducing adiposity and insulin resistance in mice and rats. Variation among mice in susceptibility to diet-induced obesity is correlated with the induction of brown adipocytes in traditional white fat depots (wBAT). Both genetic and cell biology-based experimentation have shown that the cellular origins of wBAT are different from those of interscapular-like brown adipocytes (iBAT). Do they have different functions? We have analyzed the effects of the early nutritional environment on the induction of brown adipocytes in inguinal fat to test the hypothesis that wBAT is primarily involved in body weight regulation. Although undernutrition during lactation severely suppresses wBAT at 21 days of age, undernourished mice fed a normal chow diet ad libitum at weaning recovered their normal wBAT and iBAT systems as young adults. The function of wBAT does not seem to be uniquely devoted to body weight regulation.