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Metabolic impact of adipose and hepatic glycerol channels aquaporin 7 and aquaporin 9

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 627–634 (2008)Cite this article

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

  • Aquaporins 7 and 9 act as glycerol channels in adipocytes and the liver, respectively

  • The coordinated metabolic regulation of these channels seems closely associated with glycerol and glucose metabolism

  • Impairment or lack of function of aquaporin 7 might have a causal role in obesity and diabetes mellitus

  • 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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Figure 1: The structure of aquaporins.
Figure 2: Lipogenesis and lipolysis in adipocytes.
Figure 3: AQP7 is a PPARγ target molecule.
Figure 4: Coordinated regulation of adipocyte AQP7 and liver AQP9 in a fasting state.
Figure 5: Schematic representation of the mechanism related to obesity and type 2 diabetes in the presence of AQP7 suppression.

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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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Authors and Affiliations

  1. N Maeda is a Research Fellow of Metabolic Medicine and Specialist Registrar in Internal Medicine, T Funahashi is Associate Professor of Metabolic Medicine, and I Shimomura is Professor of Metabolic Medicine in the Graduate School of Medicine, Osaka University, Osaka, Japan.,

    Norikazu Maeda, Tohru Funahashi & Iichiro Shimomura

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  1. Norikazu Maeda
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Correspondence to Norikazu Maeda.

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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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