Dietary Cholesterol Worsens Adipose Tissue Macrophage Accumulation and Atherosclerosis in Obese LDL Receptor–Deficient Mice

Abstract

Objective-Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease.Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor-deficient (LDLR Ϫ/Ϫ ) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis. Methods and Results-LDLRϪ/Ϫ mice were fed chow, high-fat, high-carbohydrate (diabetogenic) diets without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers, and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation, and local inflammation were observed in intraabdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group. Conclusions-Obesity-induced

Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner

“…However, two previous studies that used dietary cholesterol feeding to induce elevated plasma SAA concentrations have shown increased atherosclerosis development in LDL receptordeficient mice that correlated with increased SAA concentrations. 15,17 Our data combined with the literature suggest that elevated SAA concentrations contribute causally to the development of atherosclerosis.…”

“…Several recent animal studies have proposed that SAA promotes increased atherosclerosis development, [15][16][17] although the mechanism is unknown. To date there are no data suggesting a pro-atherogenic role for CRP, but CRP is not an acute phase reactant in mice, which limits the interpretation of this data.…”

Dietary cholesterol and egg yolks: Not for patients at risk of vascular disease

“…Mechanisms of the inflammatory effects of dietary cholesterol have been investigated in animal models. Dietary cholesterol worsens macrophage accumulation in adipose tissue and atherosclerosis in LDL-receptor-deficient mice (38), and increases systemic inflammation (39). Dietary cholesterol also induces monocyte chemoattractant protein-1, contributing to hepatic steatosis (40).…”

Insulin Resistance and Cardiomyopathy

“…Numerous studies show that high cholesterol induces chronic inflammation. It is reported that the addition of a small amount of cholesterol to a western-type diet is associated with chronic systemic inflammation, as evidenced by an increase in atherosclerosis and circulating inflammatory protein levels (133,134). Specifically, a study proposes the concept that, dietary cholesterol worsens adipose tissue macrophages independent of weight gain (133).…”

“…It is reported that the addition of a small amount of cholesterol to a western-type diet is associated with chronic systemic inflammation, as evidenced by an increase in atherosclerosis and circulating inflammatory protein levels (133,134). Specifically, a study proposes the concept that, dietary cholesterol worsens adipose tissue macrophages independent of weight gain (133). This observation is consistent with the notion that adipose tissue inflammation and dysregulation of adipokines secretion contribute to the www.intechopen.com development of systemic insulin resistance (135).…”