Metabolic defense of the body weight set-point.

The energy needs of an organism are a function of the tissue mass it maintains. Interspecific comparisons indicate that energy needs are a power function of body weight (12). Much of the work described here represents an effort to ascertain whether the function relating intraspecific energy expenditure to maintained body weight takes a similar form. The evidence to date from various rat preparations suggests that although some differences may exist, the form of the function for rats is not likely to differ substantially from the interspecific function derived by Kleiber (12). What has also emerged from this work, however is evidence that both the inter- and intraspecific functions accurately predict energy needs only when the organism is at the particular body weight it normally maintains and defends. This is because a rise in weight from the normal level causes energy needs to increase at a faster rate than the relationship would predict, whereas declines in weight from this level produce greater than predicted decreases in energy expenditure. We thus propose that an animal's body weight set-point be taken as the weight at which its daily energy needs can be accurately predicted from its metabolic body size. It is only at this one body weight that the animal is normometabolic. It can then be asked whether organisms maintaining abnormally high or low body weights are suffering from regulatory dysfunctions or regulating normally but at elevated or depressed set-points. We have seen that obese Zucker rats display the same adaptive metabolic adjustments to weight loss as normal weight rats. Since the exact form of the intraspecific body weight-metabolic needs relationship has not yet been determined, we must withhold judgment as to whether Zucker fatty rats are normometabolic at their elevated body weights. Since they display an effective metabolic defense of their obesity, however, an elevated set-point, rather than regulatory failure, seems to be the more probable cause of the Zucker fatty's condition. More compelling evidence of regulation at an altered body weight set-point is provided by the LH-lesioned rat. This preparation is normometabolic at the reduced body weight it maintains, and it becomes hypermetabolic when its weight is elevated to the level of nonlesioned littermates. The obesity of the VMH-lesioned rat, on the other hand, may well stem from primary regulatory impairments.(ABSTRACT TRUNCATED AT 400 WORDS)