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Tobacco Smoke-Induced Hepatic Injury with Steatosis, Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling | OMICS International| Abstract
ISSN: 2161-0681

Journal of Clinical & Experimental Pathology
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  • Research Article   
  • J Clin Exp Pathol 2016, Vol 6(2): 269
  • DOI: 10.4172/2161-0681.1000269

Tobacco Smoke-Induced Hepatic Injury with Steatosis, Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling

Suzanne M. De La Monte1,2*, Tong M1, Agarwal AR3 and Cadenas E3
1Liver Research Center, Department of Medicine, Rhode Island Hospital and the Alpert Medical School of Brown University, USA
2Division of Neuropathology and Departments of Pathology, Neurology, and Neurosurgery, Rhode Island Hospital and the Alpert Medical School of Brown University, USA
3Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA
*Corresponding Author : Suzanne M. De La Monte, Pierre Galletti Research Building, Rhode Island Hospital, 55 Claverick Street, Room 419, Providence, RI 02903, USA, Tel: 401-444-7364, Fax: 401-444-2939, Email: [email protected]

Received Date: Mar 26, 2016 / Accepted Date: Apr 14, 2016 / Published Date: Apr 17, 2016

Abstract

Background: Alcoholic liver disease (ALD) is associated with impairments in hepatic insulin and insulin-like growth factor (IGF) signaling through cell growth, survival, and metabolic pathways. Since not all heavy drinkers develop ALD, co-factors may be important. Epidemiologic data indicate that most heavy drinkers smoke tobacco and experimental data revealed that low- level nitrosamine exposures, including those from tobacco, can cause steatohepatitis with hepatic insulin/IGF resistance and exacerbate ALD. We hypothesize that cigarette smoke (CS) exposures also cause liver injury with impaired hepatic insulin/IGF signaling, and thereby contribute to ALD. Methods: Adult male A/J mice were exposed to air for 8 weeks (A8), CS for 4 (CS4) or 8 (CS8) weeks, or CS for 8 weeks with 2 weeks recovery (CS8+R). Results: CS exposures caused progressive liver injury with disruption of the normal hepatic chord architecture, lobular inflammation, apoptosis or necrosis, micro-steatosis, sinusoidal dilatation, and nuclear pleomorphism. Histopathological liver injury scores increased significantly from A8 to CS4 and then further to CS8 (P<0.0001). The mean histological grade was also higher in CS8+R relative to A8 (P<0.0001) but lower than in CS4, reflecting partial resolution of injury by CS withdrawal. CS exposures impaired insulin and IGF-1 signaling through IRS-1, Akt, GSK-3β, and PRAS40. Livers from CS8+R mice had normalized or elevated levels of insulin receptor, pYpY-Insulin- R, 312S-IRS-1, 473S-Akt, S9-GSK-3β, and pT246-PRAS40 relative to A8, CS4, or CS8, reflecting partial recovery. Conclusion: CS-mediated liver injury and steatohepatitis with impairments in insulin/IGF signalling are reminiscent of the findings in ALD. Therefore, CS exposures (either first or second-hand) may serve as a co-factor in ALD. The persistence of several abnormalities following CS exposure cessation suggests that some aspects of CSmediated hepatic metabolic dysfunction are not readily reversible.

Keywords: Tobacco; Cigarette smoke; Steatohepatitis; Mouse model; Insulin signaling

Citation: de la Monte SM, Tong M, Agarwal AR, Cadenas E (2016) Tobacco Smoke-Induced Hepatic Injury with Steatosis, Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling. J Clin Exp Pathol 6:269. Doi: 10.4172/2161-0681.1000269

Copyright: © 2016 de la Monte SM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Review summary

  1. Mohana J
    Posted on Jul 14 2016 at 11:47 pm
    The authors report the correlation between the cigarette smoke (CS) exposition and liver injury by hepatic insulin/IGF signaling and its contribution to Alcoholic Liver Disease (ALD). The fundamentals of the introduction and arguments of the discussion are grounded in relevant and accurate literature. The description of the methodology is clear and consistent with the purpose of the study. The presentation of results is precise. The subject and the scientific approaches are interesting. It will be important to continue this work to consolidate the results and open new perspectives in treating liver diseases.
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