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

Aleksandra Rojek; Ernst-Martin Füchtbauer; Annette C. Füchtbauer; Sabina Jelen; Anders Malmendal; Robert A. Fenton; Søren Nielsen

doi:10.1152/ajpgi.00208.2012

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

Aleksandra Rojek, Ernst-Martin Füchtbauer, Annette C. Füchtbauer, Sabina Jelen, Anders Malmendal, Robert A. Fenton, Søren Nielsen

Inflammation, Metabolism and Oxidation

31 Citations (Scopus)

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. Fasting of the mice (24 h) induced modest dilatation of the rough endoplasmic reticulum (RER) in the periportal hepatocytes. Refeeding 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/refeeding challenge is associated with increased expression of markers of ER stress Grp78 and GADD153 and decreased glutathione levels, suggesting that ER stress may play role in 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.

Original language	English
Journal	A J P: Gastrointestinal and Liver Physiology (Online)
Volume	304
Issue number	5
Pages (from-to)	G501-15
Number of pages	15
ISSN	1522-1547
DOIs	https://doi.org/10.1152/ajpgi.00208.2012
Publication status	Published - 1 Mar 2013

Keywords

Amino Acids
Animals
Aquaporins
Azo Compounds
Blotting, Western
Coloring Agents
DNA
Endoplasmic Reticulum, Rough
Fasting
Glycogen
Glycosylation
Hepatocytes
Homeostasis
Immunohistochemistry
Liver
Magnetic Resonance Spectroscopy
Mice
Mice, Knockout
RNA
Real-Time Polymerase Chain Reaction
Tissue Fixation
Vacuoles

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10.1152/ajpgi.00208.2012

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Rojek, A., Füchtbauer, E-M., Füchtbauer, A. C., Jelen, S., Malmendal, A., Fenton, R. A., & Nielsen, S. (2013). Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after amino acid feeding. A J P: Gastrointestinal and Liver Physiology (Online), 304(5), G501-15. https://doi.org/10.1152/ajpgi.00208.2012

Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after amino acid feeding. / Rojek, Aleksandra; Füchtbauer, Ernst-Martin; Füchtbauer, Annette C. et al.

In: A J P: Gastrointestinal and Liver Physiology (Online), Vol. 304, No. 5, 01.03.2013, p. G501-15.

Research output: Contribution to journal › Journal article › Research › peer-review

Rojek, A, Füchtbauer, E-M, Füchtbauer, AC, Jelen, S, Malmendal, A, Fenton, RA & Nielsen, S 2013, 'Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after amino acid feeding', A J P: Gastrointestinal and Liver Physiology (Online), vol. 304, no. 5, pp. G501-15. https://doi.org/10.1152/ajpgi.00208.2012

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title = "Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after amino acid feeding",

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. Fasting of the mice (24 h) induced modest dilatation of the rough endoplasmic reticulum (RER) in the periportal hepatocytes. Refeeding 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/refeeding challenge is associated with increased expression of markers of ER stress Grp78 and GADD153 and decreased glutathione levels, suggesting that ER stress may play role in 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.",

keywords = "Amino Acids, Animals, Aquaporins, Azo Compounds, Blotting, Western, Coloring Agents, DNA, Endoplasmic Reticulum, Rough, Fasting, Glycogen, Glycosylation, Hepatocytes, Homeostasis, Immunohistochemistry, Liver, Magnetic Resonance Spectroscopy, Mice, Mice, Knockout, RNA, Real-Time Polymerase Chain Reaction, Tissue Fixation, Vacuoles",

author = "Aleksandra Rojek and Ernst-Martin F{\"u}chtbauer and F{\"u}chtbauer, {Annette C.} and Sabina Jelen and Anders Malmendal and Fenton, {Robert A.} and S{\o}ren Nielsen",

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doi = "10.1152/ajpgi.00208.2012",

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

AU - Rojek, Aleksandra

AU - Füchtbauer, Ernst-Martin

AU - Füchtbauer, Annette C.

AU - Jelen, Sabina

AU - Malmendal, Anders

AU - Fenton, Robert A.

AU - Nielsen, Søren

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. Fasting of the mice (24 h) induced modest dilatation of the rough endoplasmic reticulum (RER) in the periportal hepatocytes. Refeeding 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/refeeding challenge is associated with increased expression of markers of ER stress Grp78 and GADD153 and decreased glutathione levels, suggesting that ER stress may play role in 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. Fasting of the mice (24 h) induced modest dilatation of the rough endoplasmic reticulum (RER) in the periportal hepatocytes. Refeeding 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/refeeding challenge is associated with increased expression of markers of ER stress Grp78 and GADD153 and decreased glutathione levels, suggesting that ER stress may play role in 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.

KW - Amino Acids

KW - Animals

KW - Aquaporins

KW - Azo Compounds

KW - Blotting, Western

KW - Coloring Agents

KW - DNA

KW - Endoplasmic Reticulum, Rough

KW - Fasting

KW - Glycogen

KW - Glycosylation

KW - Hepatocytes

KW - Homeostasis

KW - Immunohistochemistry

KW - Liver

KW - Magnetic Resonance Spectroscopy

KW - Mice

KW - Mice, Knockout

KW - RNA

KW - Real-Time Polymerase Chain Reaction

KW - Tissue Fixation

KW - Vacuoles

U2 - 10.1152/ajpgi.00208.2012

DO - 10.1152/ajpgi.00208.2012

M3 - Journal article

C2 - 23275615

SN - 1522-1547

VL - 304

SP - G501-15

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

IS - 5

ER -

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

Abstract

Keywords

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