Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice

Chih Wen Lin, Hao Zhang, Min Li, Xiwen Xiong, Xi Chen, Xiaoyun Chen, X. Dong, Xiao-Ming Yin

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

Background & Aims: Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. Methods: C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. Results: In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. Conclusions: These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury.

Original languageEnglish
Pages (from-to)993-999
Number of pages7
JournalJournal of Hepatology
Volume58
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Autophagy
Fatty Liver
Pharmacology
Carbamazepine
Wounds and Injuries
Liver
Sirolimus
Ethanol
Chloroquine
High Fat Diet
Lipids
Intraperitoneal Injections
Inbred C57BL Mouse
Organelles
Insulin Resistance
Hepatocytes
Triglycerides
Insulin
Glucose
Enzymes

Keywords

  • Alcohol
  • Carbamazepine
  • Hepatic steatosis
  • High fat diet
  • Macroautophagy

ASJC Scopus subject areas

  • Hepatology

Cite this

Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice. / Lin, Chih Wen; Zhang, Hao; Li, Min; Xiong, Xiwen; Chen, Xi; Chen, Xiaoyun; Dong, X.; Yin, Xiao-Ming.

In: Journal of Hepatology, Vol. 58, No. 5, 05.2013, p. 993-999.

Research output: Contribution to journalArticle

Lin, Chih Wen ; Zhang, Hao ; Li, Min ; Xiong, Xiwen ; Chen, Xi ; Chen, Xiaoyun ; Dong, X. ; Yin, Xiao-Ming. / Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice. In: Journal of Hepatology. 2013 ; Vol. 58, No. 5. pp. 993-999.
@article{9f5ff6aec8d84afaae484c93be4329e6,
title = "Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice",
abstract = "Background & Aims: Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. Methods: C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. Results: In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. Conclusions: These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury.",
keywords = "Alcohol, Carbamazepine, Hepatic steatosis, High fat diet, Macroautophagy",
author = "Lin, {Chih Wen} and Hao Zhang and Min Li and Xiwen Xiong and Xi Chen and Xiaoyun Chen and X. Dong and Xiao-Ming Yin",
year = "2013",
month = "5",
doi = "10.1016/j.jhep.2013.01.011",
language = "English",
volume = "58",
pages = "993--999",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice

AU - Lin, Chih Wen

AU - Zhang, Hao

AU - Li, Min

AU - Xiong, Xiwen

AU - Chen, Xi

AU - Chen, Xiaoyun

AU - Dong, X.

AU - Yin, Xiao-Ming

PY - 2013/5

Y1 - 2013/5

N2 - Background & Aims: Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. Methods: C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. Results: In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. Conclusions: These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury.

AB - Background & Aims: Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. Methods: C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. Results: In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. Conclusions: These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury.

KW - Alcohol

KW - Carbamazepine

KW - Hepatic steatosis

KW - High fat diet

KW - Macroautophagy

UR - http://www.scopus.com/inward/record.url?scp=84876287362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876287362&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2013.01.011

DO - 10.1016/j.jhep.2013.01.011

M3 - Article

VL - 58

SP - 993

EP - 999

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 5

ER -