Aarhus University Seal / Aarhus Universitets segl

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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.
Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Pages (from-to)G501-G515
Number of pages15
Publication statusPublished - 1 Mar 2013

See relations at Aarhus University Citationformats

ID: 52446714