Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction.
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.
Thakker
Geeta D
GD
Dept. of Medicine, Baylor College of Medicine, 6565 Fannin, M.S. A-601, Houston, TX 77030, USA.
Frangogiannis
Nikolaos G
NG
Bujak
Marcin
M
Zymek
Paul
P
Gaubatz
John W
JW
Reddy
Anilkumar K
AK
Taffet
George
G
Michael
Lloyd H
LH
Entman
Mark L
ML
Ballantyne
Christie M
CM
D000818:Animals; D004032:Diet / Q000009:adverse effects*; D005260:Female; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D020257:Ventricular Remodeling