lysophosphatidylethanolamine and Inflammation

Topics: Animals; Cell Physiological Phenomena; Drug Design; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Inflammation; Insulin; Insulin Secretion; Lysophospholipids; Neurotransmitter Agents; Propylene Glycols; Receptors, G-Protein-Coupled; Sphingosine

Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions.. The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders.. We determined the concentrations of 8 lysophosphatidylcholines, 11 lysophosphatidylethanolamines, and 7 lysophosphatidylinositols in the plasma of 34 normal-weight and 38 obese subjects randomly assigned to consume corn oil (control) or n-3 PUFA-rich fish oil (3 g/d; n = 15-19/group) for 90 d. Blood samples were collected on the last day of the study under fasting conditions and 6 h after a high-fat meal (1135 kcal, 86 g fat) challenge. The profile of secreted lysophospholipids was studied in HepG2 cells under palmitate-induced steatosis.. Obese and normal-weight subjects had different profiles of plasma lysophospholipids. A multivariate combination of the 26 lysophospholipids could discriminate between normal-weight and obese subjects with an accuracy of 98%. The high-fat meal challenge altered the concentration of plasma lysophosphatidylcholines in an oil treatment-dependent manner in normal-weight but not obese subjects, suggesting that obesity impairs the sensitivity of lysophospholipid metabolism to n-3 PUFAs. Noncytotoxic steatosis in HepG2 cells affected the secretion pattern of lysophospholipids, partially resembling the changes observed in the plasma of obese subjects.. Obesity has a substantial impact on lysophospholipid metabolism, altering the plasma lysophospholipid profile and abolishing its sensitivity to dietary n-3 PUFAs. These effects could contribute to the onset or progression of alterations associated with obesity, such as inflammation, insulin resistance, and fatty liver disease. This trial was registered at www.controlled-trials.com as ISRCTN96712688.

Topics: Adult; Diet, High-Fat; Dietary Fats; Fatty Acids, Omega-3; Fatty Liver; Female; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Lysophospholipids; Male; Middle Aged; Obesity

Lysophospholipids (LPLs) are small bioactive lipid molecules characterized by a single carbon chain and a polar head group. LPLs have recently shown to be involved in many physiological and pathological processes such as nervous system regulation. In our previous studies, a porcine liver decomposition product (PLDP) has been identified as a substance that improves cognitive function at old ages. This PLDP is a rich source of LPLs, including lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). This study was designed to evaluate the anti-inflammatory effect of these LPLs on lipopolysaccharide (LPS)-stimulated SIM-A9 microglial cells in terms of cytokine expression and oxidative stress and to investigate the potential mechanisms underlying these effects. SIM-A9 cells were pretreated with LPLs prior to LPS stimulation, and the anti-inflammatory potential of the LPLs in LPS-induced SIM-A9 cells was examined. Pretreatment with LPLs significantly inhibited the LPS-induced expression of IL-6 in SIM-A9 cells. Furthermore, oxidative-related protein, NADPH oxidase 2 (Nox2) levels were markedly increased in the LPS-treated cells, and pretreatment with LPC and LPE significantly reduced to basal levels. In addition, LPS-induced ROS production was eliminated in apocynin-treated cells, indicating that ROS production was dependent on Nox2. Our findings revealed that pretreatment with LPC and LPE decreased LPS-stimulated ROS production. These results indicated that LPC and LPE exerted significant protective effects against LPS-induced inflammation and oxidative stress in SIM-A9 cell.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Survival; Inflammation; Interleukin-6; Lipopolysaccharides; Lysophosphatidylcholines; Lysophospholipids; Mice; Microglia; NADPH Oxidase 2; Oxidative Stress; Reactive Oxygen Species