Question: 

Atherosclerosis is the major cause of myocardial infarction and stroke. An important risk factor in the development of atherosclerotic lesions is obesity. The obese adipose tissue secretes adipokines and adipocytokines that might regulate endothelial function.

Methodology: 

We analyzed the adipose tissue of atherosclerotic LDLR^-/- mice after high-fat diet feeding. LDLR^-/--mice were fed a high-fat and high-cholesterol diet (45% calories from fat, 0.21% cholesterol) for 20 weeks. A separate cohort of mice received a specifically adapted control diet.

Results: 

All mice on high-fat diet developed a marked increase in body weight. Blood glucose, LDL-cholesterol and triglyceride levels were significantly elevated. Nutritionally induced obesity resulted in a higher amount of white adipose tissue and a higher leptin mRNA and protein expression after high-fat diet. This was confirmed in LDLR^-/- mice. In addition, the pro-inflammatory adipocytokine resistin was strongly induced by high-fat diet. Expression of the vasoprotective adiponectin and the mainly H₂O₂-producing NADPH oxidase NOX4 was unaffected by high-fat diet feeding. In contrast, we found a significant induction of CD31, which supports a higher vascularization in these obese adipose tissues. In addition, we could show an increased mRNA expression of superoxide dismutases SOD1 and SOD2, suggesting activation of detoxifying, antioxidative mechanisms in adipose tissue.

Conclusion: 

We could show a dysregulation of pro-inflammatory adipocytokines in the adipose tissue of atherosclerotic LDLR^-/--mice. Our study provides a novel link between atherosclerosis and adipose tissue inflammation.