Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control

Abstract

Aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) encompass a subfamily of aquaporins that allow the movement of water and other small solutes, especially glycerol, through cell membranes. Adipose tissue constitutes a major source of glycerol via AQP7. We have recently reported that, in addition to the well-known expression of AQP7 in adipose tissue, AQP3 and AQP9 are also expressed in omental and subcutaneous fat depots. Moreover, insulin and leptin act as regulators of aquaglyceroporins through the PI3K/Akt/mTOR pathway. AQP3 and AQP7 appear to facilitate glycerol efflux from adipose tissue while reducing the glycerol influx into hepatocytes via AQP9 to prevent the excessive lipid accumulation and the subsequent aggravation of hyperglycemia in human obesity. This Extra View focuses on the control of glycerol release by aquaglyceroporins in the adipose tissue and briefly discusses the importance of glycerol as a substrate for hepatic gluconeogenesis, pancreatic insulin secretion and cardiac ATP production.

An emerging consensus on aquaporin translocation as a regulatory mechanism

“…Evidence for negative feedback regulation in lipolytic states to restrict glycerol release from fat cells by restricting AQP7 expression comes from treatment of cells with leptin, isoprenaline and carboxymethyl chitin (Rodriguez et al, 2011a). It is also thought that insulin regulates AQP7 levels, but the evidence is contradictory and there may be divergent effects of insulin on the regulation of all aquaglyceroporins in humans compared to rodents (Kishida et al, 2001, Rodriguez et al, 2011b.…”

“…The aquaglyceroporin, AQP7, is responsible (with AQP3) for the majority of glycerol transport across the membranes of adipose tissue (Rodriguez et al, 2011a) and signalling pathways, including phosphatidylinositol 3-kinase, have been associated with the regulation of aquaglyceroporin transcription (Kishida et al, 2001). Evidence for negative feedback regulation in lipolytic states to restrict glycerol release from fat cells by restricting AQP7 expression comes from treatment of cells with leptin, isoprenaline and carboxymethyl chitin (Rodriguez et al, 2011a).…”

Relative CO2/NH3 selectivities of mammalian aquaporins 0–9

“…Knocking out AQP7 leads to obesity (22) and insulin resistance (39,54). As to the potential role of the NH 3 permeability of AQP7, it is well known that intense exercise can lead to increases of [NH 3 ] in the arterial plasma that may approach levels toxic to the brain (2) if not opposed.…”

Homozygosity for aquaporin 7 G264V in three unrelated children with hyperglyceroluria and a mild platelet secretion defect

“…It was recently suggested that AQP3 and AQP9 represent additional pathways for transport of glycerol in human adipocytes and that these AQPs are therefore potentially responsible for AQP7 redundancy. 22 Here we present the cases of three children from unrelated families. All three children had psychomotor retardation of unknown etiology, pronounced renal glycerol loss (hyperglyceroluria), and a subclinical, platelet-dense granule secretion defect.…”