Toll-like receptor 4 deficiency decreases atherosclerosis but does not protect against inflammation in obese low-density lipoprotein receptor-deficient mice.

Objective: Obesity is associated with insulin resistance, chronic low-grade inflammation, and atherosclerosis. Toll-like receptor 4 (TLR4) participates in the cross talk between inflammation and insulin resistance, being activated by both lipopolysaccharide and saturated fatty acids. The present study was undertaken to determine whether TLR4 deficiency has a protective role in inflammation, insulin resistance, and atherosclerosis induced by a diabetogenic diet.

Reduced vascular nitric oxide-cGMP signaling contributes to adipose tissue inflammation during high-fat feeding.

Objective: Obesity is characterized by chronic inflammation of adipose tissue, which contributes to insulin resistance and diabetes. Although nitric oxide (NO) signaling has antiinflammatory effects in the vasculature, whether reduced NO contributes to adipose tissue inflammation is unknown. We sought to determine whether (1) obesity induced by high-fat (HF) diet reduces endothelial nitric oxide signaling in adipose tissue, (2) reduced endothelial nitric oxide synthase (eNOS) signaling is sufficient to induce adipose tissue inflammation independent of diet, and (3) increased cGMP signaling can block adipose tissue inflammation induced by HF feeding.

Antioxidants inhibit the ability of lysophosphatidylcholine to regulate proteoglycan synthesis.

Objective: We previously have shown that lysophosphatidylcholine (lysoPC) regulates proteoglycan synthesis by vascular smooth muscle cells (SMCs). Given the accumulating evidence for reactive oxygen species (ROS) as mediators of a variety of effects of lysoPC, the present study evaluates the potential role of ROS as intermediate molecules in the regulation of proteoglycan synthesis by lysoPC.

Methods And Results: LysoPC (10 micromol/L) was found to stimulate rapid and sustained generation of ROS by SMC, as indicated using a fluorescent probe for measuring intracellular oxidants and fluorescence-activated cell sorting.