BODY FAT REGULATION: IDENTIFICATION OF HUMORAL FACTORS

In 1953 Kennedy proposed the lipostatic theory for the control of body weight by regulation of total body energy stores. A subsequent parabiosis experiment implicated a blood borne factor in the feedback regulation of energy balance suggested that development of obesity led to the production of a circulating "satiety factor". The factor carried information on the size of body fat stores to the hypothalamus which then controlled food itake to correct energy balance. Recently we have reported a specific loss of fat from parabiotic partners of obese rats, independently of a significant change in food intake. This implies that, in a situation of severe obesity, a humoral factor is released to inhibit further fat deposition. Whether the loss of fat is secondary to development of insulin resistance in adipocytes remains to be determined. However, this data may be evidence for humoral agents that play a role in regulation of body fat independently of long-term control of food intake. A series of experiments has been designed using animal models that are either parabiotic partners of obese rats or are rats that are recovering from food deprivation. In each situation adipocyte lipid metabolism and sensitivity towards lipogenic and lipolytic agents will be examined. We hope to determine whether body fat is regulated, in part, by changes in sensitivity towards humoral factors that would promote either lipid deposition or lipid mobilization. The responses of mature rats, maintaining a stable body weight, will be compared with those of young rats that are in a dynamic phase of growth. In addition we intend to use an in vitro bioassay to partially purify the anti-lipogenic agent that is produced by obese rats. The proposed experiments provide a novel approach for elucidating mechanisms that may contribute towards the regulation of body fat content at a "set-point".