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

Seth Martin, Atif Qasim, Muredach P. Reilly

Research output: Contribution to journalArticle

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

Fingerprint

Leptin
Cardiovascular Diseases
Obesity
Inflammation
C-Reactive Protein
Insulin Resistance
Inflammation Mediators
Adiposity
Wounds and Injuries
Adipocytes
Innate Immunity
Type 2 Diabetes Mellitus
Pancreas
Interleukin-6
Myocardium

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Leptin Resistance. A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease. / Martin, Seth; Qasim, Atif; Reilly, Muredach P.

In: Journal of the American College of Cardiology, Vol. 52, No. 15, 07.10.2008, p. 1201-1210.

Research output: Contribution to journalArticle

@article{16f1f92e259447e1a5ec9502bc161e21,
title = "Leptin Resistance. A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease",
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.",
keywords = "atherosclerosis, cardiovascular disease, inflammation, leptin resistance, obesity",
author = "Seth Martin and Atif Qasim and Reilly, {Muredach P.}",
year = "2008",
month = "10",
day = "7",
doi = "10.1016/j.jacc.2008.05.060",
language = "English (US)",
volume = "52",
pages = "1201--1210",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "15",

}

TY - JOUR

T1 - Leptin Resistance. A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease

AU - Martin, Seth

AU - Qasim, Atif

AU - Reilly, Muredach P.

PY - 2008/10/7

Y1 - 2008/10/7

N2 - 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.

AB - 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.

KW - atherosclerosis

KW - cardiovascular disease

KW - inflammation

KW - leptin resistance

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=52949129178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52949129178&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2008.05.060

DO - 10.1016/j.jacc.2008.05.060

M3 - Article

C2 - 18926322

AN - SCOPUS:52949129178

VL - 52

SP - 1201

EP - 1210

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 15

ER -