Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis

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

doi:10.1016/j.bbrc.2007.02.129

Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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-α), 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 PPARα, 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.

Original language	English
Pages (from-to)	53-59
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	356
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2007.02.129
Publication status	Published - 27 Apr 2007

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10.1016/j.bbrc.2007.02.129

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title = "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-α), 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 PPARα, 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.",

keywords = "Cytokines, Lipoprotein lipase, NO-1886, Nutritional steatohepatitis, Peroxisome proliferator-activated receptor",

author = "Jun Yu and Chu, {Eagle S.H.} and Hui, {Alex Y.} and Cheung, {Kin F.} and Chan, {Henry L.Y.} and Leung, {Wai K.} and Farrell, {Geoffrey C.} and Sung, {Joseph J.Y.}",

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T1 - Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis

AU - Yu, Jun

AU - Chu, Eagle S.H.

AU - Hui, Alex Y.

AU - Cheung, Kin F.

AU - Chan, Henry L.Y.

AU - Leung, Wai K.

AU - Farrell, Geoffrey C.

AU - Sung, Joseph J.Y.

PY - 2007/4/27

Y1 - 2007/4/27

N2 - 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-α), 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 PPARα, 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.

AB - 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-α), 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 PPARα, 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.

KW - Cytokines

KW - Lipoprotein lipase

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KW - Nutritional steatohepatitis

KW - Peroxisome proliferator-activated receptor

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JO - Biochemical and Biophysical Research Communications

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Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis

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