Aquaglyceroporins: implications in adipose biology and obesity

Abstract

Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological processes. Their primary function is to facilitate the bidirectional transfer of water and small solutes across biological membranes in response to osmotic gradients. Aquaglyceroporins, a subset of the AQP family, are the only mammalian proteins with the ability to permeate glycerol. For a long time, AQP7 has been the only aquaglyceroporin associated with the adipose tissue, which is the major source of circulating glycerol in response to the energy demand. AQP7 dysregulation was positively correlated with obesity onset and adipocyte glycerol permeation through AQP7 was appointed as a novel regulator of adipocyte metabolism and whole-body fat mass. Recently, AQP3, AQP9, AQP10 and AQP11 were additionally identified in human adipocytes and proposed as additional glycerol pathways in these cells. This review contextualizes the importance of aquaglyceroporins in adipose tissue biology and highlights aquaglyceroporins' unique structural features which are relevant for the design of effective therapeutic compounds. We also refer to the latest advances in the identification and characterization of novel aquaporin isoforms in adipose tissue. Finally, considerations on the actual progress of aquaporin research and its implications on obesity therapy are suggested.

Beyond water homeostasis: Diverse functional roles of mammalian aquaporins

“…There are up to 13 mammalian AQPs, which are found in most tissues with functions ranging from the regulation of renal water balance [1], brain-fluid homeostasis [2], triglyceride cycling between adipocytes and the liver [3] and structural integrity of the eye lens [4]. Because of this, understanding AQP function is crucial for the study of healthy ageing as well as the onset of many disease states such as brain swelling following stroke or head injury [5], nephrogenic diabetes insipidus [6,7], cataracts [8], obesity [9], cancer cell proliferation and migration [10] and tumour angiogenesis [11]. Many of these functions and diseases involve either permeability of molecules other than water, or a function of the AQP other than facilitating membrane permeability.…”

Genetic Variants Associated With Uncontrolled Blood Pressure on Thiazide Diuretic/β‐Blocker Combination Therapy in the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) and INVEST (International Verapamil‐SR Trandolapril Study) Trials

“…Association of AQP9 with BP regulation is unclear; however, 1 study found that it was upregulated in preeclamptic placenta . AQP9, in coordination with AQP7, may regulate adiposity and glucose homeostasis . Notably, other members of the aquaporin family (AQP1, AQP2, and AQP4) have been associated with BP in animal studies …”

Assay of Endocannabinoid Uptake

“…The radioactive label in arachidonoyl [1][2][3] H]ethanolamine is in the ethanolamine moiety, which is quickly cleaved and then incorporated into phospholipids [ 7 -9 ]. Therefore, the radioactive signal associated to the organic phase of the cell pellets is derived from free [ H]glycerol freely and rapidly moves out of the cell via aquaporins, leading to a "loss" of intracellular radioactive signal [ 10 ]. The remaining signal is therefore only dependent on intracellular arachidonoyl [1,2, H]glycerol [ 7 ].…”