Leptin Resistance. A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease

Seth S. Martin, Atif Qasim, Muredach P. Reilly

Research output: Contribution to journalReview articlepeer-review

Abstract

Leptin is an adipocyte-derived hormone and cytokine that regulates energy balance through a wide range of functions, including several that are important to cardiovascular health. Increased circulating leptin, a marker of leptin resistance, is common in obesity and independently associated with insulin resistance and cardiovascular disease (CVD) in humans. The mechanisms of leptin resistance include genetic mutation, leptin self-regulation, limited tissue access, and cellular or circulating molecular regulation. Evidence suggests that central leptin resistance causes obesity and that obesity-induced leptin resistance injures numerous peripheral tissues, including liver, pancreas, platelets, vasculature, and myocardium. This metabolic- and inflammatory-mediated injury may result from either resistance to leptin's action in selective tissues, or excess leptin action from adiposity-associated hyperleptinemia. In this sense, the term "leptin resistance" encompasses a complex pathophysiological phenomenon. The leptin axis has functional interactions with elements of metabolism, such as insulin, and inflammation, including mediators of innate immunity, such as interleukin-6. Leptin is even purported to physically interact with C-reactive protein, resulting in leptin resistance, which is particularly intriguing, given C-reactive protein's well-studied relationship to cardiovascular disease. Given that plasma levels of leptin and inflammatory markers are correlated and also predict cardiovascular risk, it is conceivable that part of this risk may be mediated through leptin resistance-related insulin resistance, chronic inflammation, type II diabetes, hypertension, atherothrombosis, and myocardial injury. Leptin resistance and its interactions with metabolic and inflammatory factors, therefore, represent potential novel diagnostic and therapeutic targets in obesity-related cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)1201-1210
Number of pages10
JournalJournal of the American College of Cardiology
Volume52
Issue number15
DOIs
StatePublished - Oct 7 2008
Externally publishedYes

Keywords

  • atherosclerosis
  • cardiovascular disease
  • inflammation
  • leptin resistance
  • obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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