Leptin's Physiologic Role: Does the Emperor of Energy Balance Have No Clothes?

Publication date: Available online 22 June 2017
Source:Cell Metabolism
Author(s): Jeffrey S. Flier, Eleftheria Maratos-Flier
The discovery of the obese gene and the demonstration that its encoded protein leptin can reverse obesity due to genetic deficiency of the hormone were landmark discoveries in endocrinology and metabolism. Regarding leptin's role in physiology, it is now established that falling leptin levels are a key signal of the starved state in mice and humans. Repleting leptin reverses the starvation signal both in physiologic starvation and in obesity resulting from genetic leptin deficiency. Since its discovery, it has also been hypothesized that rising leptin levels caused by overfeeding provide a physiologic signal that orchestrates resistance to obesity. Although still widely believed, and possibly true in some circumstances, this aspect of leptin physiology has not been experimentally demonstrated. It will be important to determine whether leptin or as yet undiscovered factors are responsible for the well-documented capacity for physiologic resistance to overfeeding.

Teaser

Leptin, the product of the ob gene, effectively treats leptin-deficient obesity. Flier et al. discuss two distinct aspects of leptin physiology. Whereas reduced levels with starvation evoke key adaptations to starvation, a role for rising leptin with overfeeding in resistance to obesity has not been experimentally demonstrated.


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