title: Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice.
abstract: OBJECTIVE
  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.
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
authors: Chih-Wen
authors: CW
authors: Lin
authors: Hao
authors: H
authors: Zhang
authors: Min
authors: M
authors: Li
authors: Xiwen
authors: X
authors: Xiong
authors: Xi
authors: X
authors: Chen
authors: Xiaoyun
authors: X
authors: Chen
authors: Xiaocheng C
authors: XC
authors: Dong
authors: Xiao-Ming
authors: XM
authors: Yin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002220:Carbamazepine / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D002220:Carbamazepine; D000431:Ethanol; D002738:Chloroquine; D020123:Sirolimus