Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction

Geeta D. Thakker, Nikolaos G. Frangogiannis, Marcin Bujak, Paul Zymek, John W. Gaubatz, Anilkumar K. Reddy, George Taffet, Lloyd H. Michael, Mark L. Entman, Christie M. Ballantyne

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Epidemiological studies indicate that obesity, insulin resistance, and diabetes are important comorbidities of patients with ischemic heart disease and increase mortality and development of congestive heart failure after myocardial infarction. Although ob/ob and db/db mice are commonly used to study obesity with insulin resistance or diabetes, mutations in the leptin gene or its receptor are rarely the cause of obesity in humans, which is, instead, primarily a consequence of dietary and lifestyle factors. Therefore, we used a murine model of diet-induced obesity to examine the physiological effects of obesity and the inflammatory and healing response of diet-induced obese (DIO) mice after myocardial ischemia-reperfusion injury. DIO mice developed hyperinsulinemia and insulin resistance and hepatic steatosis, with significant ectopic lipid deposition in the heart and cardiac hypertrophy in the absence of significant changes in blood pressure. The mRNA levels of chemokines at 24 h and cytokines at 24 and 72 h of reperfusion were higher in DIO than in lean mice. In granulation tissue at 72 h of reperfusion, macrophage density was significantly increased, whereas neutrophil density was reduced, in DIO mice compared with lean mice. At 7 days of reperfusion, collagen deposition in the scar was significantly reduced and left ventricular (LV) dilation and cardiac hypertrophy were increased, indicative of adverse LV remodeling, in infarcted DIO mice. Characterization of a murine diet-induced model of obesity and insulin resistance that satisfies many aspects commonly observed in human obesity allows detailed examination of the adverse cardiovascular effects of diet-induced obesity at the molecular level.

Original languageEnglish (US)
Pages (from-to)H2504-H2514
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number5
DOIs
StatePublished - 2006

Keywords

  • Cardiac lipotoxicity
  • Insulin resistance
  • Ischemia-reperfusion injury
  • Left ventricular remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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