Abstract
The discovery of aquaporins, which are plasma-membrane-associated water channels, has greatly influenced the medical sciences. So far, thirteen aquaporins have been identified in humans. Among them, types 3, 7, 9, and 10 are subcategorized as aquaglyceroporins, which enable the transport of glycerol as well as water. Although aquaporins have a proven crucial role in water homeostasis, the physiological and pathological importance of aquaporins as glycerol channels is not fully understood. Adipocytes are a major source of glycerol, one of the substrates for hepatic gluconeogenesis. Aquaporin subtypes 7 and 9 (AQP7 and AQP9) are the glycerol channels in adipocytes and hepatocytes, respectively. The coordinated regulation of these channels leads to the optimum balance between release of glycerol by adipocytes and its uptake by the liver. In addition, studies of AQP7 and AQP9 knockout or knockdown mice have clearly demonstrated in vivo the pathophysiological relevance of glycerol channels through effects on glycerol metabolism. Associations between various AQP7 gene mutations and obesity in humans have also been shown. Thus, further research of these two aquaporins might uncover novel targets for therapy.
Key Points
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Aquaporins 7 and 9 act as glycerol channels in adipocytes and the liver, respectively
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The coordinated metabolic regulation of these channels seems closely associated with glycerol and glucose metabolism
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Impairment or lack of function of aquaporin 7 might have a causal role in obesity and diabetes mellitus
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Peroxisome proliferator-activated receptor γ ligands might ameliorate insulin resistance partly by increasing the activity of aquaporin 7 in adipose tissue
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Acknowledgements
We thank all our colleagues, especially Toshiyuki Hibuse, Ken Kishida, Hiroshi Kuriyama, and Tadashi Nakamura, for their contributions to the literature reviewed here.
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Maeda, N., Funahashi, T. & Shimomura, I. Metabolic impact of adipose and hepatic glycerol channels aquaporin 7 and aquaporin 9. Nat Rev Endocrinol 4, 627–634 (2008). https://doi.org/10.1038/ncpendmet0980
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DOI: https://doi.org/10.1038/ncpendmet0980
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