Glycerol efflux from adipocytes to the liver is crucial for lipid and glucose homeostasis. Aquaporin 7 (AQP7) is a glycerol channel serving as a gateway of glycerol release and a regulator of adipocyte metabolism.
A study done by Catalan et al. measured the gene expression of AQP7 in visceral adipose tissue (VAT) and AQP9 in liver biopsies obtained from 20 women (Catalan et al., 2008). It was observed that mRNA levels of AQP7 in VAT were up-regulated in obese patients, while AQP9 were down-regulated in obese type 2 diabetes mellitus (T2DM) patients.
However, in AQP7 knockout mice, the development of obesity and hyperglycemia was observed. Single nucleotide polymorphisms (SNPs), such as A-953G in the AQP7 promoter, were found to be related to type 2 diabetes in 977 Caucasians (Prudente et al., 2007). The -953G promoter caused decreased transcriptional activity, as well as the ability to bind CCAAT/enhancer binding protein (C/EBP) beta transcription factor. It was suggested that down-regulation of AQP7 in adipose tissue is associated with obesity and type 2 diabetes.
In another study done by Ceperuelo-Mallafre et al., AQP7 expression levels were down-regulated in 13 severely obese women (Ceperuelo-Mallafre et al., 2007). The expression of AQP7 was found to be negatively related with proinflammatory genes such as TNFalpha. It expression levels may be positively related with the expression of PPARgamma. However, the expression of AQP7 seemed not changed in patients with type 2 diabetes.
These studies show that AQP7 is may be associated with obesity and/or type 2 diabetes. However, more studies are still needed in larger groups of patients to determine the exact role of this gene in obesity.
References:
Catalan, V., Gomez-Ambrosi, J., et al. (2008) Influence of morbid obesity and insulin resistance on gene expression levels of AQP7 in visceral adipose tissue and AQP9 in liver. Obes Surg 18, 695-701.
Ceperuelo-Mallafre, V., Miranda, M., et al. (2007) Adipose tissue expression of the glycerol channel aquaporin-7 gene is altered in severe obesity but not in type 2 diabetes. J Clin Endocrinol Metab 92, 3640-3645.
Prudente, S., Flex, E., et al. (2007) A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities. Diabetes 56, 1468-1474.
