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Leptin: 30 Years Later.

Rexford S Ahima1, Jeffrey S Flier2

  • 1Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Annual Review of Physiology
|October 3, 2025
PubMed
Summary
This summary is machine-generated.

Leptin, a hormone regulating energy balance, was discovered in 1994. While effective for rare deficiencies, leptin therapy fails in common obesity due to resistance, suggesting new treatment avenues.

Keywords:
adipose tissueimmunityleptinmetabolismneuroendocrineobesity

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Area of Science:

  • Metabolic Science
  • Endocrinology
  • Neuroscience

Background:

  • Leptin, encoded by the ob gene, is an adipocyte-secreted hormone crucial for regulating energy balance.
  • Its discovery revolutionized understanding of metabolic regulation, identifying central circuitry responsive to peripheral signals.
  • Initially seen as preventing obesity, falling leptin levels are now recognized as signaling starvation.

Purpose of the Study:

  • To review the discovery and physiological roles of leptin.
  • To discuss the mechanisms and implications of leptin resistance in common obesity.
  • To evaluate the therapeutic potential of leptin and related strategies.

Main Methods:

  • Literature review of leptin research since its discovery.
  • Analysis of studies on leptin signal transduction and resistance.
  • Evaluation of clinical outcomes for leptin therapy in various conditions.

Main Results:

  • Leptin discovery transformed metabolic science, revealing key regulatory pathways.
  • Leptin resistance, partially characterizing common obesity, hinders therapeutic efficacy.
  • Leptin therapy is effective in congenital leptin deficiency but not common obesity.

Conclusions:

  • Understanding leptin's dual role in energy balance and starvation signaling is critical.
  • Molecular mechanisms of leptin resistance in common obesity require further elucidation.
  • Reducing hyperleptinemia may offer a promising therapeutic strategy for common obesity.