Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice.
Fatty liver or hepatic steatosis is a common health problem associated with abnormal liver function and increased susceptibility to ischemia/reperfusion injury. The objective of this study was to investigate the effect of the fatty acid synthase inhibitor cerulenin on hepatic function in steatotic o...
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doaj-229e859089e94eec9ee0ffe47d9596fa2020-11-25T00:48:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7598010.1371/journal.pone.0075980Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice.Gang ChengArun P PalanisamyZachary P EvansAlton G SutterLan JinInderjit SinghHarold MayMichael G SchmidtKenneth D ChavinFatty liver or hepatic steatosis is a common health problem associated with abnormal liver function and increased susceptibility to ischemia/reperfusion injury. The objective of this study was to investigate the effect of the fatty acid synthase inhibitor cerulenin on hepatic function in steatotic ob/ob mice. Different dosages of cerulenin were administered intraperitoneally to ob/ob mice for 2 to 7 days. Body weight, serum AST/ALT, hepatic energy state, and gene expression patterns in ob/ob mice were examined. We found that cerulenin treatment markedly improved hepatic function in ob/ob mice. Serum AST/ALT levels were significantly decreased and hepatic ATP levels increased in treated obese mice compared to obese controls, accompanied by fat depletion in the hepatocyte. Expression of peroxisome proliferator-activated receptors α and γ and uncoupling protein 2 were suppressed with cerulenin treatment and paralleled changes in AST/ALT levels. Hepatic glutathione content were increased in some cases and apoptotic activity in the steatotic livers was minimally changed with cerulenin treatment. In conclusion, these results demonstrate that fatty acid synthase blockade constitutes a novel therapeutic strategy for altering hepatic steatosis at non-stressed states in obese livers.http://europepmc.org/articles/PMC3785413?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gang Cheng Arun P Palanisamy Zachary P Evans Alton G Sutter Lan Jin Inderjit Singh Harold May Michael G Schmidt Kenneth D Chavin |
spellingShingle |
Gang Cheng Arun P Palanisamy Zachary P Evans Alton G Sutter Lan Jin Inderjit Singh Harold May Michael G Schmidt Kenneth D Chavin Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. PLoS ONE |
author_facet |
Gang Cheng Arun P Palanisamy Zachary P Evans Alton G Sutter Lan Jin Inderjit Singh Harold May Michael G Schmidt Kenneth D Chavin |
author_sort |
Gang Cheng |
title |
Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. |
title_short |
Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. |
title_full |
Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. |
title_fullStr |
Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. |
title_full_unstemmed |
Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. |
title_sort |
cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Fatty liver or hepatic steatosis is a common health problem associated with abnormal liver function and increased susceptibility to ischemia/reperfusion injury. The objective of this study was to investigate the effect of the fatty acid synthase inhibitor cerulenin on hepatic function in steatotic ob/ob mice. Different dosages of cerulenin were administered intraperitoneally to ob/ob mice for 2 to 7 days. Body weight, serum AST/ALT, hepatic energy state, and gene expression patterns in ob/ob mice were examined. We found that cerulenin treatment markedly improved hepatic function in ob/ob mice. Serum AST/ALT levels were significantly decreased and hepatic ATP levels increased in treated obese mice compared to obese controls, accompanied by fat depletion in the hepatocyte. Expression of peroxisome proliferator-activated receptors α and γ and uncoupling protein 2 were suppressed with cerulenin treatment and paralleled changes in AST/ALT levels. Hepatic glutathione content were increased in some cases and apoptotic activity in the steatotic livers was minimally changed with cerulenin treatment. In conclusion, these results demonstrate that fatty acid synthase blockade constitutes a novel therapeutic strategy for altering hepatic steatosis at non-stressed states in obese livers. |
url |
http://europepmc.org/articles/PMC3785413?pdf=render |
work_keys_str_mv |
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