Mechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice

Abstract

Journal of Lipid Research Volume 54, 20132775 systems encompasses species with both ester and ether linkages [(the latter of which are collectively termed alkyl glycerol phosphates (AGP)] as well as differences in hydrocarbon chain length and saturation ( 1 ). LPAs exhibit a broad range of biological activities that are initiated by LPA selective G-protein-coupled cell-surface receptors. Some LPA responses may also be mediated by the nuclear peroxisome proliferator ␥ receptor and the receptor for advanced glycan end products ( 2 ). LPA is present in blood plasma ( 3 ) and accumulates in human atheromas and in experimentally induced atherosclerotic lesions in mice ( 4 ). Studies using LPA receptor-defi cient mice and LPAdirected small molecule therapeutics identify roles for LPA signaling in atherothrombosis and vascular injury responses ( 5-7 ). A common variant in the PPAP2B gene encoding the LPA inactivating cell surface integral membrane enzyme lipid phosphate phosphatase 3 (LPP3) may predict LPP3 mRNA expression in blood cells and is strongly associated with increased human cardiovascular disease risk. In mice, PPAP2B expression in vascular smooth muscle cells is protective against vascular injury responses ( 6, 8 ). Together, these studies point to an important role for LPA in human cardiovascular disease and focus attention on the Lysophosphatidic acid (LPA) denotes a family of radyl hydrocarbon-substituted derivatives of glycerol 3-phosphate. Structural diversity in LPA species identifi ed in biological

An obligatory role for neurotensin in high-fat-diet-induced obesity

“…For hepatic TG and cholesterol measurements, liver tissues were collected from male NT +/+ and NT −/− mice fed HFD for 24 weeks after weaning; TG and cholesterol were extracted as described previously 39 and analyzed by LC-MS coupled with electrospray ionization tandem using stable isotope dilution 40 performed on AB Sciex 4000 Q-Trap instruments. Fasting plasma glucose was analyzed using a Glucose Colorimetric Assay Kit II (BioVision) and insulin using a Mouse Insulin ELISA kit (Mercodia Inc, Winston Salem, NC).…”

Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis

“…Freeze-dried and powdered Tg6F or control (EV) tomatoes were added to the diet at 2.2% by weight as previously described ( 11 ). LysoPC or LPA were mixed into chow as previously described ( 39 ), and the oral specifi c autotaxin inhibitor PF8380 ( 42,43 ) was similarly added to chow. Prior to harvesting of organs, the mice were perfused under anesthesia to remove all blood ( 11, 39 ), and organs were by guest, on May 12, 2018 www.jlr.org Downloaded from mice were fed standard mouse chow supplemented with LPA 18:2 or WD ( Fig.…”

ORMDL/serine palmitoyltransferase stoichiometry determines effects of ORMDL3 expression on sphingolipid biosynthesis

“…Prior to extraction, a mixture of C17 sphingolipids was added to each sample (125 pmol/sample, Avanti sphingolipid mix #1) as internal standards. Sphingolipids were quantitated by HPLC electrospray ionization tandem mass spectrometry using selected ion monitoring on an ABSciex 4000 Q-Trap instrument as described previously (13)(14)(15). Total phospholipids for each sample were measured using a modifi ed Ames and Dubin assay ( 16 ), as previously described ( 12 ).…”