Ghrelin-mediated pathway in Apolipoprotein-E deficient mice: a survival system.

Renal diseases interfere with the regulation of several metabolic pathways including dyslipidemia. The latter includes increased triglycerides, very low-density lipoprotein levels and decreased high-density lipoproteins. These lipoproteins change during renal injury. Apolipoprotein-E deficient mice (ApoE-/-) are considered a very well accepted model of hypercholesterolemia with marked renal pathological alterations. Ghrelin hormone is mainly secreted from the stomach when the stomach is empty, but it is also found in the kidney. In this organ it has autocrine and/or paracrine roles determining glomerular filtration rate, tubular phosphate and sodium reabsorption. Interestingly, it has been demonstrated that ghrelin levels increase after fasting. This mechanism induces an interaction with sirtuin 1 (SIRT1)/p53 pathway suggesting a link between ghrelin and SIRT1 in the regulation of salt and water metabolism. The mechanisms of ghrelin-induced SIRT1 expression are not yet fully understood. Recent studies indicate that SIRT1 exerts renoprotective properties against kidney diseases. This could be a very interesting point for underlining the important role of the ghrelin-SIRT1 system. Water movement across biological cell membranes is enhanced or facilitated by tetrameric membrane-bound channels, named aquaporin (AQP) family, and in particular, AQP1 and AQP2 proteins. In this study, we evaluated the possible pathway existing among the ghrelin/SIRT1/AQP1/AQP2 system in APOE-/- mice in order to clarify or stress the role played by said system in renal diseases associated to aging with or without comorbities. The results could provide a basis for considering ghrelin as a new target for therapeutic strategies of renal injury.