DOI: 10.1152/ajpgi.00041.2002. Fasting in α<sub>1</sub>-antitrypsin deficient liver: constitutive activation of autophagy

Fasting in α1-antitrypsin deficient liver: constitutive activation of autophagy

10.1152/ajpgi.00041.2002

Crossref journal-article

American Physiological Society

American Journal of Physiology-Gastrointestinal and Liver Physiology (24)

Abstract

α1-Antitrypsin (α1-AT) deficiency causes severe liver injury in a subgroup of patients. Liver injury is thought to be caused by retention of a polymerized mutant α1-ATZ molecule in the endoplasmic reticulum (ER) of hepatocytes and is associated with an intense autophagic response. However, there is limited information about what physiologic stressors might influence liver injury. In this study, we examined the effect of fasting in the PiZ mouse model of α1-AT deficiency, because fasting is a well-characterized physiological stressor and a known stimulus for autophagy. Results show that there is a marked increase in fat accumulation and in α1-AT-containing globules in the liver of the PiZ mouse induced by fasting. Although fasting induced a marked autophagic response in wild-type mice, the autophagic response was already activated in PiZ mice and did not further increase with fasting. PiZ mice also had a significantly decreased tolerance for prolonged fasting compared with wild-type mice (PiZ mice 0% survival of 72-h fast; wild-type 100% survivial). These results demonstrate an altered response to stress in the α1-AT-deficient liver, including inability to further increase an activated autophagic response, a developmental state-specific increase in α1-AT-containing globules, and increased mortality.

Bibliography

Teckman, J. H., An, J.-K., Loethen, S., & Perlmutter, D. H. (2002). Fasting in Î±1-antitrypsin deficient liver: constitutive activation of autophagy. American Journal of Physiology-Gastrointestinal and Liver Physiology, 283(5), G1156âG1165.

Authors 4

Jeffrey H. Teckman (first)
Jae-Koo An (additional)
Scott Loethen (additional)
David H. Perlmutter (additional)

References 26 Referenced 67

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Dates

Type	When
Created	10 years, 5 months ago (March 3, 2015, 6:20 p.m.)
Deposited	5 years, 11 months ago (Sept. 8, 2019, 8:34 p.m.)
Indexed	4 months ago (April 22, 2025, 4:11 a.m.)
Issued	22 years, 9 months ago (Nov. 1, 2002)
Published	22 years, 9 months ago (Nov. 1, 2002)
Published Print	22 years, 9 months ago (Nov. 1, 2002)

Funders 0

None

BibTeX

@article{Teckman_2002, title={Fasting in α1-antitrypsin deficient liver: constitutive activation of autophagy}, volume={283}, ISSN={1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00041.2002}, DOI={10.1152/ajpgi.00041.2002}, number={5}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Teckman, Jeffrey H. and An, Jae-Koo and Loethen, Scott and Perlmutter, David H.}, year={2002}, month=nov, pages={G1156–G1165} }

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