
-   Glycerol efflux from adipocytes is regulated by the aquaglyceroporin AQP7, which is translocated upon hormone stimulation. Biochemical analyses combined with ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation. These data suggest that AQP7 mobility in adipocytes is dependent on perilipin 1 and protein kinase A [PMID: 27832861].
-   AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in a model of high-fat diet in streptozocin-induced diabetic rats and in vitro in response to hyperglycemia and hyperlipidemia. Treatment with an antidiabetic agent, metformin, suppressed the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic beta-cells and subsequent insulin secretion in type 2 diabetes mellitus [PMID: 34303707].
-   AQP7 plays a key role in glycerol permeability, as the inhibition of AQP7 resulted in a 55% decrease in glycerol diffusion across the sperm membrane. Importantly, this glycerol permeability impairment was evident in spermatozoa from asthenozoospermic individuals, suggesting the dysregulation of AQP7-mediated glycerol transport, despite similar AQP7 levels. Conversely, the AQP7 expression increased in capacitated sperm, compared to non-capacitated sperm. Hence, AQP7-mediated permeability may serve as a valuable indicator of sperm motility, and be crucial in sperm function [PMID: 37566082].

## Summary

AQP7 is primarily involved in mediating the transport of glycerol across cell membranes, a critical process in maintaining energy homeostasis and glucose levels [CS: 10]. In healthy conditions, AQP7 facilitates the release of glycerol from adipocytes into the bloodstream, where it is used for gluconeogenesis in the liver, thus helping to maintain normal blood glucose levels [CS: 10]. Liver toxicity or damage could potentially trigger the overexpression of AQP7 as a compensatory response to maintain metabolic homeostasis, particularly in the context of disrupted glycerol and glucose metabolism [CS: 7]. When the liver is damaged or stressed, its ability to perform normal metabolic functions, such as gluconeogenesis and lipid metabolism, can be impaired [CS: 9]. This impairment can lead to metabolic imbalances, including altered glucose levels and lipid accumulation [CS: 9]. In such a scenario, the body may respond by upregulating AQP7 to facilitate the increased transport of glycerol from adipocytes into the bloodstream, provide an enhanced supply of glycerol to the liver, supporting gluconeogenesis and helping to maintain normal blood glucose levels [CS: 7]. This increased glycerol supply is particularly vital when the liver's gluconeogenic capacity is compromised due to toxicity or damage [CS: 7]. By overexpressing AQP7, the body attempts to counteract the impaired metabolic functions of the damaged liver, striving to maintain energy balance and prevent complications like hypoglycemia [CS: 7].

The observed downregulation of AQP7 in the context of liver diseases, such as hepatocellular carcinoma (HCC), impairs this glycerol transport mechanism [CS: 9]. Reduced AQP7 expression means less glycerol is available for gluconeogenesis [CS: 9]. This potentially disrupts glucose homeostasis and exacerbates the energy deficit typically associated with liver diseases [CS: 8]. Furthermore, the decreased AQP7 expression in the liver could lead to an accumulation of glycerol in adipocytes, contributing to metabolic imbalances [CS: 8]. This scenario is particularly detrimental in liver pathologies, as the liver's ability to regulate metabolism, including gluconeogenesis and lipid catabolism, is already compromised [CS: 9].
