22(S)-hydroxy Cholesterol is a synthetic oxysterol and a modulator of the liver X receptor (LXR). [1] t prevents monocyte chemoattractant protein 1 (MCP-1) expression induced by the LXR agonist GW 3965 in primary hepatocytes and downregulates mRNA expression of the LXR target genes CD36, ACSL1, and SCD-1 in human myotubes. It decreases triacylglycerol and diacylglycerol synthesis from labeled palmitate and acetate, respectively, in human myoblasts by 50% when used at a concentration of 10 uM. 22(S)-hydroxy Cholesterol also reduces fatty acid synthase (FAS) reporter activity through an LXR response element in the promoter region in COS-1 cells transfected with RXRα and LXRα and decreases the expression of MCP-1 and CCR2 in a mouse model of chronic ethanol consumption.[1] [2] Dietary supplementation of 22(S)-hydroxy cholesterol (30 mg kg per day) leads to less body weight gain and lower liver triacylglycerol levels in rats when fed either a regular chow or high-fat diet as well as prevents an increase in plasma triacylglycerol levels resulting from a high-fat diet.[3]
10-Nitrolinoleate is the product of nitration of linoleate by NO-derived reactive species. Other nitrolinoleates detected in human plasma and urine include 9-, 12-, and 13-nitrolinoleate. Nitrolinoleates activate peroxisome proliferator-activated receptor γ (PPARγ; Ki = 133 nM), inducing CD36 expression in macrophages, adipocyte differentiation, and glucose uptake. Nitrolinoleates can also be metabolized by smooth muscle cells to produce nitrite derivatives which in turn form NO, leading to increased cGMP production and smooth muscle relaxation. Through the same mechanism, nitrolinoleate-derived NO suppresses leukocyte adhesion, in part through nitrosation of CD40. Alteratively, nitrolinoleates can act independently of NO/cGMP and PPARγ signaling to suppress neutrophil and macrophage functions.