Digestive Diseases and Sciences

, Volume 62, Issue 8, pp 2021–2034 | Cite as

Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice

  • Sulaiman R. Hamarneh
  • Byeong-Moo Kim
  • Kanakaraju Kaliannan
  • Sara A. Morrison
  • Tyler J. Tantillo
  • Qingsong Tao
  • Mussa M. Rafat Mohamed
  • Juan M. Ramirez
  • Aaron Karas
  • Wei Liu
  • Dong Hu
  • Abeba Teshager
  • Sarah Shireen Gul
  • Konstantinos P. Economopoulos
  • Atul K. Bhan
  • Madhu S. Malo
  • Michael Y. ChoiEmail author
  • Richard A. HodinEmail author
Original Article


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.


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.


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.


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.


Intestinal alkaline phosphatase Alcoholic liver disease Fatty liver Stellate cells 



Richard A. Hodin was supported by National Institute of Health grant NIH/NIDDK T32 (No. DK007754), The Ellison Foundation grant and Nutritional Obesity Research Center of Harvard (NORCH) NIH (No. P30-DK040561). We also thank the animal facility and the pathology lab at MGH for maintainance of animals and preparation of tissue sections.

Author's contribution

RAH, MYC, MSM, SRH, and BK contributed to study concept and theory; RAH, MYC, SRH, and BK contributed to research design; SRH, BK, KK, SAM, TJT, QT, MMRM, JMR, AK, WL, DH, AT, SSG, KPE, AKB, MSM, MYC, and RAH contributed to data acquisition; SRH, BK, KK, SAM, TJT, QT, MMRM, JMR, AK, WL, DH, AT, SSG, KPE, AKB, MSM, MYC, and RAH contributed to data analyses and interpretation; SRH, BK, SAM, KPE, MYC, and RAH contributed to statistical analyses; SRH, BK, CYM, and RAH contributed to drafting of the manuscript; all authors contributed to critical review of the manuscript for important intellectual content; RAH obtained funding; all authors contributed to approval of the manuscript; RAH and MYC supervised the study.

Compliance with ethical standards

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Sulaiman R. Hamarneh
    • 1
  • Byeong-Moo Kim
    • 2
  • Kanakaraju Kaliannan
    • 1
  • Sara A. Morrison
    • 1
  • Tyler J. Tantillo
    • 1
  • Qingsong Tao
    • 1
  • Mussa M. Rafat Mohamed
    • 1
  • Juan M. Ramirez
    • 1
  • Aaron Karas
    • 1
  • Wei Liu
    • 1
  • Dong Hu
    • 1
  • Abeba Teshager
    • 1
  • Sarah Shireen Gul
    • 1
  • Konstantinos P. Economopoulos
    • 1
  • Atul K. Bhan
    • 3
  • Madhu S. Malo
    • 1
  • Michael Y. Choi
    • 2
    • 4
    Email author
  • Richard A. Hodin
    • 1
    Email author
  1. 1.Department of Surgery, Harvard Medical SchoolMassachusetts General HospitalBostonUSA
  2. 2.Gastrointestinal Unit, Department of Medicine, Harvard Medical SchoolMassachusetts General HospitalBostonUSA
  3. 3.Department of Pathology, Harvard Medical SchoolMassachusetts General HospitalBostonUSA
  4. 4.Harvard Stem Cell InstituteCambridgeUSA

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