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10.1194/jlr.M057547 http://scihub22266oqcxt.onion/10.1194/jlr.M057547 C4617394!4617394 !26351364     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26351364 &cmd=llinks): Failed to open stream: HTTP request failed! 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Xanthine-based KMUP-1 improves HDL via PPAR?/SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss |pdf=|usr=}}{{26351364 }} gab.com Text Xanthine-based KMUP-1 improves HDL via PPAR /SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss JO: J Lipid Res http://www.kidney.de/pget.php?&tw=1&pmid=26351364 #FOAvip The phosphodiesterase inhibitor (PDEI)/eNOS enhancer KMUP-1, targeting G-protein coupled receptors (GPCRs), improves dyslipidemia. We compared its lipid-lowering effects with simvastatin and explored hormone-sensitive lipase (HSL) translocation in hepatic fat loss. KMUP-1 HCl (1, 2.5, and 5 mg/kg/day) and simvastatin (5 mg/kg/day) were administered in C57BL/6J male mice fed a high-fat diet (HFD) by gavage for 8 weeks. KMUP-1 inhibited HFD-induced plasma/liver TG, total cholesterol, and LDL; increased HDL/3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)/Rho kinase II (ROCK II)/PPAR?/ABCA1; and decreased liver and body weight. KMUP-1 HCl in drinking water (2.5 mg/200 ml tap water) for 1-14 or 8-14 weeks decreased HFD-induced liver and body weight and scavenger receptor class B type I expression and increased protein kinase A (PKA)/PKG/LDLRs/HSL expression and immunoreactivity. In HepG2 cells incubated with serum or exogenous mevalonate, KMUP-1 (10(-7)?10(-5) M) reversed HMGR expression by feedback regulation, colocalized expression of ABCA1/apolipoprotein A-I/LXR?/PPAR?, and reduced exogenous geranylgeranyl pyrophosphate/farnesyl pyrophosphate (FPP)-induced RhoA/ROCK II expression. A guanosine 3',5'-cyclic monophosphate (cGMP) antagonist reversed KMUP-1-induced ROCK II reduction, indicating cGMP/eNOS involvement. KMUP-1 inceased PKG and LDLRs surrounded by LDL and restored oxidized LDL-induced PKA expresion. Unlike simvastatin, KMUP-1 could not inhibit (14)C mevalonate formation. KMUP-1 could, but simvastatin could not, decrease ROCK II expression by exogenous FPP/CGPP. KMUP-1 improves HDL via PPAR?/LXR?/ABCA1/Apo-I expression and increases LDLRs/PKA/PKG/HSL expression and immunoreactivity, leading to TG hydrolysis to lower hepatic fat and body weight. Twit Text FOAVip Xanthine-based KMUP-1 improves HDL via PPAR /SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss ????J Lipid Res http://www.kidney.de/pget.php?&tw=1&pmid=26351364 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26351364 #FOAvip English Wikipedia <ref>{{Cite pmid|26351364 }}</ref> Xanthine-based KMUP-1 improves HDL via PPAR?/SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss #MMPMID26351364 Kuo KK ; Wu BN ; Liu CP ; Yang TY ; Kao LP ; Wu JR ; Lai WT ; Chen IJ J Lipid Res 2015[Nov]; 56 (11 ): 2070-84 PMID26351364 show ga The phosphodiesterase inhibitor (PDEI)/eNOS enhancer KMUP-1, targeting G-protein coupled receptors (GPCRs), improves dyslipidemia. We compared its lipid-lowering effects with simvastatin and explored hormone-sensitive lipase (HSL) translocation in hepatic fat loss. KMUP-1 HCl (1, 2.5, and 5 mg/kg/day) and simvastatin (5 mg/kg/day) were administered in C57BL/6J male mice fed a high-fat diet (HFD) by gavage for 8 weeks. KMUP-1 inhibited HFD-induced plasma/liver TG, total cholesterol, and LDL; increased HDL/3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)/Rho kinase II (ROCK II)/PPAR?/ABCA1; and decreased liver and body weight. KMUP-1 HCl in drinking water (2.5 mg/200 ml tap water) for 1-14 or 8-14 weeks decreased HFD-induced liver and body weight and scavenger receptor class B type I expression and increased protein kinase A (PKA)/PKG/LDLRs/HSL expression and immunoreactivity. In HepG2 cells incubated with serum or exogenous mevalonate, KMUP-1 (10(-7)?10(-5) M) reversed HMGR expression by feedback regulation, colocalized expression of ABCA1/apolipoprotein A-I/LXR?/PPAR?, and reduced exogenous geranylgeranyl pyrophosphate/farnesyl pyrophosphate (FPP)-induced RhoA/ROCK II expression. A guanosine 3',5'-cyclic monophosphate (cGMP) antagonist reversed KMUP-1-induced ROCK II reduction, indicating cGMP/eNOS involvement. KMUP-1 inceased PKG and LDLRs surrounded by LDL and restored oxidized LDL-induced PKA expresion. Unlike simvastatin, KMUP-1 could not inhibit (14)C mevalonate formation. KMUP-1 could, but simvastatin could not, decrease ROCK II expression by exogenous FPP/CGPP. KMUP-1 improves HDL via PPAR?/LXR?/ABCA1/Apo-I expression and increases LDLRs/PKA/PKG/HSL expression and immunoreactivity, leading to TG hydrolysis to lower hepatic fat and body weight. |ATP Binding Cassette Transporter 1/metabolism [MESH] |Animals [MESH] |Cyclic AMP-Dependent Protein Kinases/metabolism [MESH] |Cyclic GMP-Dependent Protein Kinases/metabolism [MESH] |Diet, High-Fat/adverse effects [MESH] |Drug Evaluation, Preclinical [MESH] |Hep G2 Cells [MESH] |Humans [MESH] |Hydroxymethylglutaryl CoA Reductases/metabolism [MESH] |Hyperlipoproteinemias/*drug therapy/etiology [MESH] |Hypolipidemic Agents/*pharmacology/therapeutic use [MESH] |Intra-Abdominal Fat/drug effects/physiology [MESH] |Lipoproteins, HDL/blood [MESH] |Lipoproteins, LDL/metabolism [MESH] |Liver/pathology [MESH] |Male [MESH] |Mevalonic Acid/metabolism [MESH] |Mice, Inbred C57BL [MESH] |PPAR gamma/metabolism [MESH] |Piperidines/*pharmacology/therapeutic use [MESH] |Receptors, LDL/metabolism [MESH] |Scavenger Receptors, Class B/metabolism [MESH] |Second Messenger Systems [MESH] |Sterol Esterase/metabolism [MESH]Xanthine-based KMUP-1 improves HDL via PPAR?/SR-B1, LDL via LDLRs, and(epmc).pdf DeepDyve Pubget Overpricing