High-Fructose Diet Induces Cardiac Dysfunction via Macrophage Recruitment in Adult Mice

Abstract

Cardiovascular diseases are the leading cause of death globally, including cardiac fibrosis, myocardial infarction, cardiac hypertrophy, and heart failure. High fat/ fructose induces metabolic syndrome, hypertension and obesity, which contributes to cardiac hypertrophy and fibrosis. Excessive fructose intake accelerates inflammation in different organs and tissues, and molecular and cellular mechanisms of organ and tissue injury have been demonstrated. However, the mechanisms of cardiac inflammation have not been fully documented in high-fructose diet. This study shows that there are significantly increased in cardiomyocytes size and relative wall thickness of LV in high-fructose fed adult mice. With echocardiographic analysis of cardiac function, the ejection fraction (EF%) and fractional shortening (FS%) are significantly reduced at 12 weeks after 60% high-fructose diet. The mRNA and protein levels of MCP-1 are notably increased in high-fructose treated HL-1 and primary cardiomyocyte respectively. Also, the increased protein level of MCP-1 has been detected in vivo mouse model after 12 weeks feeding, resulting in the production of pro-inflammatory makers, pro-fibrotic genes expression, and macrophage infiltration. These data demonstrate that high-fructose intake induces cardiac inflammation via macrophage recruitment in cardiomyocyte, which contributes to impair cardiac function.

Acute Intake of Fructose Increases Arterial Pressure in Humans: A Meta-Analysis and Systematic Review

“…For instance, a high dose of fructose (60% of caloric intake daily) consumption for 20–28 days remarkably increases mean arterial pressure in dogs [ 87 ]. Moreover, consumption of a 60% fructose diet in rodents decreases left ventricular ejection fraction [ 88 ]. Rodents fed 20% fructose as their daily caloric intake, more consistent with the fructose intake in the upper quintile of human subjects, did not display left ventricular diastolic dysfunction, but systolic left ventricular function remained unaffected [ 89 , 90 ].…”

The Intersection of Genetic Factors, Aberrant Nutrient Metabolism and Oxidative Stress in the Progression of Cardiometabolic Disease

“…A diet high in fructose is known to induce cardiac fibrosis and hypertrophy, likely due in part to fructose inhibiting nod-like receptor family pyrin domain containing 4 (NLRP4) a potential negative regulator of pro-inflammatory cytokine secretion [184]. On the other hand, fructose stimulates cardiac inflammation via the recruitment of macrophages to cardiomyocytes, resulting in cardiac remodeling and dysfunction [185]. In terms of sympathetic nervous system activity, a diet high in fructose elevated autonomic outflow to the heart and vasculature, which preceded any alterations in arterial pressure or blood lipids [186].…”

“…PUFAs and CVD PUFAs protect against CAD (non-human primates) [150] Fructose and CVD Fructose consumption exerts negative effects on CV health [177,[179][180][181][184][185][186][187] Human studies Dietary Fat and CAD in women Saturated and trans fats increase risk of CAD [143] Clinical PUFAs and CVD Replacement of sat. fat with veg oil reduces risk of CHD [153,155,156] n-3 PUFAs negate adverse LV remodeling after MI [161] Meta-analysis…”