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Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice.
Hamarneh, Sulaiman R; Kim, Byeong-Moo; Kaliannan, Kanakaraju; Morrison, Sara A; Tantillo, Tyler J; Tao, Qingsong; Mohamed, Mussa M Rafat; Ramirez, Juan M; Karas, Aaron; Liu, Wei; Hu, Dong; Teshager, Abeba; Gul, Sarah Shireen; Economopoulos, Konstantinos P; Bhan, Atul K; Malo, Madhu S; Choi, Michael Y; Hodin, Richard A.
Affiliation
  • Hamarneh SR; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Kim BM; Gastrointestinal Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
  • Kaliannan K; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Morrison SA; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Tantillo TJ; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Tao Q; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Mohamed MMR; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Ramirez JM; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Karas A; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Liu W; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Hu D; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Teshager A; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Gul SS; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Economopoulos KP; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Bhan AK; Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Malo MS; Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.
  • Choi MY; Gastrointestinal Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. mchoi@mgh.harvard.edu.
  • Hodin RA; Harvard Stem Cell Institute, Cambridge, MA, 02138, USA. mchoi@mgh.harvard.edu.
Dig Dis Sci ; 62(8): 2021-2034, 2017 08.
Article in En | MEDLINE | ID: mdl-28424943
ABSTRACT
BACKGROUND AND

AIMS:

Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease.

METHODS:

Mice underwent acute binge or chronic ethanol exposure to induce alcoholic liver injury and steatosis ± IAP supplementation. Liver tissue was assessed for biochemical, inflammatory, and histopathological changes. An ex vivo co-culture system was used to examine the effects of alcohol and IAP treatment in regard to the activation of hepatic stellate cells and their role in the development of alcoholic liver disease.

RESULTS:

Pretreatment with IAP resulted in significantly lower serum alanine aminotransferase compared to the ethanol alone group in the acute binge model. IAP treatment attenuated the development of alcohol-induced fatty liver, lowered hepatic pro-inflammatory cytokine and serum LPS levels, and prevented alcohol-induced gut barrier dysfunction. Finally, IAP ameliorated the activation of hepatic stellate cells and prevented their lipogenic effect on hepatocytes.

CONCLUSIONS:

IAP treatment protected mice from alcohol-induced hepatotoxicity and steatosis. Oral IAP supplementation could represent a novel therapy to prevent alcoholic-related liver disease in humans.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dietary Supplements / Alkaline Phosphatase / Fatty Liver, Alcoholic Type of study: Prognostic_studies Limits: Animals Language: En Journal: Dig Dis Sci Year: 2017 Document type: Article Affiliation country: Estados Unidos
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dietary Supplements / Alkaline Phosphatase / Fatty Liver, Alcoholic Type of study: Prognostic_studies Limits: Animals Language: En Journal: Dig Dis Sci Year: 2017 Document type: Article Affiliation country: Estados Unidos