Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis.

Abstract

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.

• Authors: Jun Yu, Eagle S H Chu, Alex Y Hui, Kin F Cheung, Henry L Y Chan, Wai K Leung, Geoffrey C Farrell, Joseph J Y Sung
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 356 Issue 1 Pg. 53-9 (Apr 27 2007) ISSN: 0006-291X [Print] United States
• PMID: 17350593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Hypolipidemic Agents
• Interleukin-6
• Lipoproteins, HDL
• Organophosphorus Compounds
• PPAR gamma
• RNA, Messenger
• Thiobarbituric Acid Reactive Substances
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide
• Cholesterol
• Methionine
• Cyclooxygenase 2
• Lipoprotein Lipase

Topics

• Animals
• Benzamides (administration & dosage, pharmacology)
• Cholesterol (blood)
• Choline Deficiency
• Cyclooxygenase 2 (genetics, metabolism)
• Diet (adverse effects)
• Enzyme Activation (drug effects)
• Fatty Liver (blood, etiology, prevention & control)
• Gene Expression (drug effects)
• Hypolipidemic Agents (administration & dosage, pharmacology)
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Lipogenesis (genetics)
• Lipoprotein Lipase (genetics, metabolism)
• Lipoproteins, HDL (blood)
• Liver (drug effects, metabolism, pathology)
• Male
• Methionine (deficiency)
• Mice
• Mice, Inbred C57BL
• Organophosphorus Compounds (administration & dosage, pharmacology)
• PPAR gamma (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)