Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis
Copyright policy )Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis
Dietary model of steatohepatitis was established by feeding mice a methionine choline deficient (MCD) diet. Mice on MCD or control diet for 3 weeks were treated with or without NO-1886, a newly synthetic lipoprotein lipase (LPL) activator. In a separate experiment, NO-1886 was given after pre-treatment with 3 weeks of MCD diet. NO-1886 significantly reduced MCD-induced inflammation by repressing levels of hepatic lipid peroxides and pro-inflammatory tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). In addition, NO-1886 dampened hepatic steatosis via accelerating fatty acid oxidation caused by enhanced expression of PPARalpha, cytochrome P450-10 (Cyp4a10), and Acyl-CoA oxidase (ACO). It failed to regulate genes of fatty acid uptake and synthesis pathways. In conclusion, NO-1886 ameliorated and induced regression of experimental steatohepatitis via increasing endogenous LPL activation resulting in suppression on pro-inflammatory factors and reduction of hepatic fatty acids. These findings indicate that NO-1886 is a potential therapeutic agent for steatohepatitis.
- University of Hong Kong China (People's Republic of)
- Australian National University Australia
- Hospital Authority China (People's Republic of)
- University of Hong Kong (香港大學) China (People's Republic of)
- Prince of Wales Hospital China (People's Republic of)
Male, Tumor Necrosis Factor-alpha - genetics - metabolism, Organophosphorus Compounds - administration & dosage - pharmacology, lipid peroxide, Benzamides - administration & dosage - pharmacology, Gene Expression, PPAR gamma - genetics - metabolism, Inbred C57BL, NO-1886, Mice, Methionine, acyl coenzyme A oxidase, Lipoprotein Lipase - genetics - metabolism, Species Index: Mus, cyclooxygenase 2, Messenger - genetics - metabolism, Cholesterol - blood, Hypolipidemic Agents, Lipogenesis - genetics, HDL - blood, Gene Expression - drug effects, Interleukin-6 - genetics - metabolism, cytochrome P450 4A, Intercellular Adhesion Molecule-1, Hypolipidemic Agents - administration & dosage - pharmacology, Choline Deficiency, Cholesterol, Liver, peroxisome pr Cytokines, Liver - drug effects - metabolism - pathology, Benzamides, Intercellular Adhesion Molecule-1 - genetics - metabolism, Diet - adverse effects, Lipoproteins, HDL, RNA, Messenger - genetics - metabolism, Methionine - deficiency, Lipoproteins, cytochrome p450 4a10, Nutritional steatohepatitis, Enzyme Activation - drug effects, interleukin 6, lipoprotein lipase, Thiobarbituric Acid Reactive Substances - metabolism, Keywords: 4 [(4 bromo 2 cyanophenyl)carbamoyl]benzylphosphonic acid diethyl ester, choline, Animals, methionine, Fatty Liver - blood - etiology - prevention & control, Interleukin-6, Lipogenesis, Peroxisome proliferator-activated receptor, Diet, Enzyme Activation, Fatty Liver, Mice, Inbred C57BL, Lipoprotein Lipase, Cyclooxygenase 2, RNA, fatty acid, Lipoproteins, HDL - blood, Cyclooxygenase 2 - genetics - metabolism
Male, Tumor Necrosis Factor-alpha - genetics - metabolism, Organophosphorus Compounds - administration & dosage - pharmacology, lipid peroxide, Benzamides - administration & dosage - pharmacology, Gene Expression, PPAR gamma - genetics - metabolism, Inbred C57BL, NO-1886, Mice, Methionine, acyl coenzyme A oxidase, Lipoprotein Lipase - genetics - metabolism, Species Index: Mus, cyclooxygenase 2, Messenger - genetics - metabolism, Cholesterol - blood, Hypolipidemic Agents, Lipogenesis - genetics, HDL - blood, Gene Expression - drug effects, Interleukin-6 - genetics - metabolism, cytochrome P450 4A, Intercellular Adhesion Molecule-1, Hypolipidemic Agents - administration & dosage - pharmacology, Choline Deficiency, Cholesterol, Liver, peroxisome pr Cytokines, Liver - drug effects - metabolism - pathology, Benzamides, Intercellular Adhesion Molecule-1 - genetics - metabolism, Diet - adverse effects, Lipoproteins, HDL, RNA, Messenger - genetics - metabolism, Methionine - deficiency, Lipoproteins, cytochrome p450 4a10, Nutritional steatohepatitis, Enzyme Activation - drug effects, interleukin 6, lipoprotein lipase, Thiobarbituric Acid Reactive Substances - metabolism, Keywords: 4 [(4 bromo 2 cyanophenyl)carbamoyl]benzylphosphonic acid diethyl ester, choline, Animals, methionine, Fatty Liver - blood - etiology - prevention & control, Interleukin-6, Lipogenesis, Peroxisome proliferator-activated receptor, Diet, Enzyme Activation, Fatty Liver, Mice, Inbred C57BL, Lipoprotein Lipase, Cyclooxygenase 2, RNA, fatty acid, Lipoproteins, HDL - blood, Cyclooxygenase 2 - genetics - metabolism
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