Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after feeding amino acids

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Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after feeding amino acids. / Rojek, Aleksandra; Füchtbauer, Ernst-Martin; Füchtbauer, Annette; Jelen, Sabina; Malmendal, Anders; Fenton, Robert A.; Nielsen, Soren.

In: American Journal of Physiology: Gastrointestinal and Liver Physiology, Vol. 304, No. 5, 01.03.2013, p. G501-G515.

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Rojek, Aleksandra ; Füchtbauer, Ernst-Martin ; Füchtbauer, Annette ; Jelen, Sabina ; Malmendal, Anders ; Fenton, Robert A. ; Nielsen, Soren. / Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after feeding amino acids. In: American Journal of Physiology: Gastrointestinal and Liver Physiology. 2013 ; Vol. 304, No. 5. pp. G501-G515.

Bibtex

@article{efe46c8db26f4093ac41d8555ec2bb5f,
title = "Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after feeding amino acids",
abstract = "Aquaporin 11 (AQP11) is a protein channel expressed intracellularly in multiple organs, yet its physiological function is unclear. Aqp11 knockout (KO) mice die early due to malfunction of the kidney, a result of hydropic degeneration of proximal tubule cells. Here we report the generation of liver-specific Aqp11 KO mice, allowing us to study the role of AQP11 protein in liver of mice with normal kidney function. The unchallenged liver-specific Aqp11 KO mice have normal longevity, their livers appeared normal, and the plasma biochemistries revealed only a minor defect in lipid handling. 24 h fasting of the mice induced modest dilatation of the rough endoplasmic reticulum (RER) in the periportal hepatocytes. Re-feeding with standard mouse chow induced rapid generation of large RER-derived vacuoles in Aqp11 KO mice hepatocytes. Similar effects were observed following oral administration of pure protein or larger doses of various amino acids. The fasting/re-feeding challenge is associated with increased expression of markers of ER-stress Grp78 and GADD153, and decreased glutathione levels, suggesting that ER-stress may underlie the development of vacuoles in the AQP11-deficient hepatocytes. NMR-based metabolome analysis of livers from mice subject to amino acid challenge showed decreased amount of extractable metabolites in the AQP11-deficient livers, and particularly a decrease in glucose levels. In conclusion, in the liver, deletion of AQP11 results in disrupted RER homeostasis and increased sensitivity to RER injury upon metabolic challenge with amino acids.",
author = "Aleksandra Rojek and Ernst-Martin F{\"u}chtbauer and Annette F{\"u}chtbauer and Sabina Jelen and Anders Malmendal and Fenton, {Robert A.} and Soren Nielsen",
year = "2013",
month = mar,
day = "1",
doi = "10.1152/ajpgi.00208.2012",
language = "English",
volume = "304",
pages = "G501--G515",
journal = "American Journal of Physiology: Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "5",

}

RIS

TY - JOUR

T1 - Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after feeding amino acids

AU - Rojek, Aleksandra

AU - Füchtbauer, Ernst-Martin

AU - Füchtbauer, Annette

AU - Jelen, Sabina

AU - Malmendal, Anders

AU - Fenton, Robert A.

AU - Nielsen, Soren

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Aquaporin 11 (AQP11) is a protein channel expressed intracellularly in multiple organs, yet its physiological function is unclear. Aqp11 knockout (KO) mice die early due to malfunction of the kidney, a result of hydropic degeneration of proximal tubule cells. Here we report the generation of liver-specific Aqp11 KO mice, allowing us to study the role of AQP11 protein in liver of mice with normal kidney function. The unchallenged liver-specific Aqp11 KO mice have normal longevity, their livers appeared normal, and the plasma biochemistries revealed only a minor defect in lipid handling. 24 h fasting of the mice induced modest dilatation of the rough endoplasmic reticulum (RER) in the periportal hepatocytes. Re-feeding with standard mouse chow induced rapid generation of large RER-derived vacuoles in Aqp11 KO mice hepatocytes. Similar effects were observed following oral administration of pure protein or larger doses of various amino acids. The fasting/re-feeding challenge is associated with increased expression of markers of ER-stress Grp78 and GADD153, and decreased glutathione levels, suggesting that ER-stress may underlie the development of vacuoles in the AQP11-deficient hepatocytes. NMR-based metabolome analysis of livers from mice subject to amino acid challenge showed decreased amount of extractable metabolites in the AQP11-deficient livers, and particularly a decrease in glucose levels. In conclusion, in the liver, deletion of AQP11 results in disrupted RER homeostasis and increased sensitivity to RER injury upon metabolic challenge with amino acids.

AB - Aquaporin 11 (AQP11) is a protein channel expressed intracellularly in multiple organs, yet its physiological function is unclear. Aqp11 knockout (KO) mice die early due to malfunction of the kidney, a result of hydropic degeneration of proximal tubule cells. Here we report the generation of liver-specific Aqp11 KO mice, allowing us to study the role of AQP11 protein in liver of mice with normal kidney function. The unchallenged liver-specific Aqp11 KO mice have normal longevity, their livers appeared normal, and the plasma biochemistries revealed only a minor defect in lipid handling. 24 h fasting of the mice induced modest dilatation of the rough endoplasmic reticulum (RER) in the periportal hepatocytes. Re-feeding with standard mouse chow induced rapid generation of large RER-derived vacuoles in Aqp11 KO mice hepatocytes. Similar effects were observed following oral administration of pure protein or larger doses of various amino acids. The fasting/re-feeding challenge is associated with increased expression of markers of ER-stress Grp78 and GADD153, and decreased glutathione levels, suggesting that ER-stress may underlie the development of vacuoles in the AQP11-deficient hepatocytes. NMR-based metabolome analysis of livers from mice subject to amino acid challenge showed decreased amount of extractable metabolites in the AQP11-deficient livers, and particularly a decrease in glucose levels. In conclusion, in the liver, deletion of AQP11 results in disrupted RER homeostasis and increased sensitivity to RER injury upon metabolic challenge with amino acids.

U2 - 10.1152/ajpgi.00208.2012

DO - 10.1152/ajpgi.00208.2012

M3 - Journal article

C2 - 23275615

VL - 304

SP - G501-G515

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 5

ER -