How adipocytes integrate surplus caloric intake with caloric storage: Lessons from Morgan Spurlock and some French geese

Purpose of review: In this review, the physiologic roles of the hyperleptinemia induced by expansion of the adipose tissue mass is analyzed. Endogenous hyperleptinemia is an immediate response to overnutrition, and it increases progressively in proportion to the expansion of the fat mass, suggesting that it is fulfilling some physiologic role related to this expansion. The co-existence of diet-induced obesity (DIO) and hyperleptinemia has been considered paradoxical because of the fact that exogenously-induced hyperleptinemia dramatically reduces food intake and body fat. While the discrepancy between the effects of exogenous and endogenous hyperleptinemia has been ascribed to a leptin resistance factor generated by DIO, the more plausible explanation is that the effects of a hormone administered for experimental purposes in the absence of a physiologic need do not duplicate the effects of endogenous hypersecretion of the hormone in response to such a need. Just as exogenous insulin causes hypoglycemia in a normal fasting individual, whereas endogenous hyperglycemia induced by a meal corrects hyperglycemia without causing hypoglycemia, so the anorexia and weight loss induced by exogenous leptin does not duplicate the effects of endogenous hyperleptinemia responding to DIO. Recent findings: The review analyzes a possible role of DIO-induced hyperleptinemia, the only known cause of hypersecretion of this adipocyte hormone. The evidence points to a sophisticated regulatory system which permits the ingestion of surplus calories in an effort to prolong survival in famine without exceeding the storage capacity of the adipocytes and inflicting metabolic trauma to the nonadipose tissues of the body by maldistribution of the caloric excess. At the hypothalamic level, it is proposed that leptin restrains the level of overnutrition, ie, it prevents the "supersizing" exemplified by the recent Morgan Spurlock film, "Supersize Me" and by force-fed geese used for the production of paté de fois gras. At the same time, hyperleptinemia increases fatty acid oxidation in nonadipose tissues, thereby reducing the risk of fatty acid overload with lipotoxicity and lipoapoptosis. Summary: As a result of hyperleptinemia, obesity can be tolerated for extended periods of time without damage to the nonadipose tissues of the body, embodied in the metabolic syndrome. In addition, leptin may be involved in determining when the positive caloric balance and body weight wanes, replaced by caloric equilibrium and the body weight plateau.