Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia.

BACKGROUND: Hypertriglyceridemia increases risk for atherosclerotic cardiovascular disease and may contribute to atherosclerosis by changing circulating monocyte phenotypes. High-dose n-3 polyunsaturated fatty acids reduce blood triglyceride levels. Effects of triglyceride-lowering therapy on monocyte phenotypes are not well known. OBJECTIVE: We examined effects of n-3 polyunsaturated fatty acid treatments (eicosapentaenoic acid [EPA] plus docosapentaenoic acid [MAT9001] vs EPA ethyl esters [EPA-EE]) on monocyte phenotypes in individuals with hypertriglyceridemia. METHODS: Individuals with triglycerides 200 to 400 mg/dL were recruited. Subjects received 2 treatments in randomized order for 14 days each: MAT9001 and EPA-EE, at 4 g/d. At 2 days before the start of, and on the last day of, each treatment, nile red staining for lipids and phenotypes of each monocyte subset were examined by flow cytometry after an overnight fast and postprandially after a high-fat meal. RESULTS: Treatment with MAT9001 or EPA-EE reduced fasting triglyceride levels and decreased proportions of intermediate monocytes. Only MAT9001 decreased postprandial blood triglyceride levels, lowered fasting nile red levels, indicating less lipid in classical and intermediate monocytes, and reduced postprandial CD11c levels on nonclassical monocytes. MAT9001 and EPA-EE each reduced fasting and postprandial CD11c and CD36 levels on classical and intermediate monocytes and postprandial CCR5 levels on intermediate and nonclassical monocytes, with no significant differences between the 2 treatments. CONCLUSIONS: Treatment with MAT9001 in individuals with hypertriglyceridemia reduced fasting nile red staining for lipids in classical and intermediate monocytes. MAT9001 and EPA-EE each improved fasting and postprandial monocyte phenotypes, which could potentially help to protect against atherosclerosis.

Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency.

OBJECTIVES: High-fat diet (HFD) feeding in mice is characterized by accumulation of αß T cells in adipose tissue. However, the contribution of αß T cells to obesity-induced inflammation of skeletal muscle, a major organ of glucose uptake, is unknown. This study was undertaken to evaluate the effect of αß T cells on insulin sensitivity and inflammatory state of skeletal muscle and adipose tissue in obesity. Furthermore, we investigated whether CD4+IFNγ+ (TH1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity. METHODS: Mice lacking αß T cells (T cell receptor beta chain-deficient [TCRb-/-] mice) were fed HFD for 12 weeks. Obesity-induced skeletal muscle and adipose tissue inflammation was assessed by flow cytometry and quantitative RT-PCR. To investigate the effect of TH1 cells on skeletal muscle and adipose tissue inflammation and metabolic functions, we injected 5×10(5) TH1 cells or PBS weekly over 12 weeks into HFD-fed TCRb-/- mice. We also cultured C2C12 myofibers and 3T3-L1 adipocytes with TH1-conditioned medium. RESULTS: We showed that similar to adipose tissue, skeletal muscle of obese mice have higher αß T cell content, including TH1 cells. TCRb-/- mice were protected against obesity-induced hyperglycemia and insulin resistance. We also demonstrated suppressed macrophage infiltration and reduced inflammatory cytokine expression in skeletal muscle and adipose tissue of TCRb-/- mice on HFD compared to wild-type obese controls. Adoptive transfer of TH1 cells into HFD-fed TCRb-/- mice resulted in increased skeletal muscle and adipose tissue inflammation and impaired glucose metabolism. TH1 cells directly impaired functions of C2C12 myotubes and 3T3-L1 adipocytes in vitro. CONCLUSIONS: We conclude that reduced adipose tissue and skeletal muscle inflammation in obese TCRb-/- mice is partially attributable to the absence of TH1 cells. Our results suggest an important role of TH1 cells in regulating inflammation and insulin resistance in obesity.