Rationale for the existence of additional adipostatic hormones

Parabiosis studies with obese rodents demonstrated that circulating factors are involved in the long-term control of food intake and energy balance. M ore than 40 years ago it was hypothesized that rats made obese by hypothala mic or dietary means, as well as genetically obese fa/fa rats and db/db mic e, produce a circulating factor that either inhibits food intake or acts me tabolically to reduce the fat content of non-obese ad libitum-fed partners. However, none of these obese rodents showed a significant change in weight when parabiosed to a normal animal. It was therefore postulated that these obese rodents produced a circulating lipostatic factor but were unable to respond to it. In contrast, genetically obese ob/ob mice were thought to be deficient in the circulating signal, as they lost weight when parabiosed t o lean or obese db/db mice. The discovery of leptin suggested that the circ ulating lipostatic signal had been identified. However, a closer look at th e outcome of the parabiotic studies reveals that leptin alone does not expl ain all of the findings of the parabiotic experiments. Another (or more tha n one) as yet unidentified factor(s) may be involved in energy balance regu lation. The evidence for the existence of further leptin-like hormones come s from observations in which the direct effect of leptin has been eliminate d or can be excluded.