Endocrine Abstracts

We have previously shown that in pancreatic ductal epithelial cells, the expression of the water channel aquaporin-1 is under the control of the oxysterol receptor liver X receptor β. The aim of the present study was to investigate water balance in mice lacking each LXR isoform.

Given free access to water, LXRβ−/− mice demonstrated an abnormal daily excretion of highly diluted urine, polyuria, with increased water intake compared to WT animals, polydipsia. After 24-h dehydration, LXRβ−/− mice were able to decrease the 24-h urine volume and to concentrate urine but the urine output was higher than that in dehydrated WT mice. Interestingly, in LXRα−/− there were no detectable defects in urine volume and concentration.

Polyuria and polydipsia are the clinical features of a condition called diabetes insipidus that according to the etiology may be classified in central and nephrogenic. The first one results from a defective production/secretion of the antidiuretic hormone arginine vasopressin while the nephrogenic one is due to a defective vasopressin action in the kidney.

To pinpoint the genesis of the LXRβ-diabetes insipidus, WT and LXRβ−/− mice were injected intraperitoneally with arginine vasopressin. There was no change in the urine volume after 3 and 6 h, but the urine osmolality was significantly increased at 6 h in LXRβ−/− mice indicating a partially conserved kidney capability to respond to vasopressin. Therefore the central vasopressin production was investigated. Surprisingly, in LXRβ−/− mice, there was an important loss of vasopressin-producing neurons both in the supraoptic and in paraventricular nuclei of the hypothaluamus. In addition, the vasopressin content of the 24-h urine was lower than that in WT mice, indicating a central genesis of their diabetes insipidus. Moreover, in addition to the central effects, there was a nephrogenic involvement since aquaporin-1 expression in the kidney was reduced in LXRβ−/− mice.

In conclusion this paper shows that LXRβ plays a crucial role in regulating water balance both centrally and peripherally and it can be suggested both as genetic predisposition in human central diabetes insipidus and as possible therapeutic target in disorders of water balance.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported however funding details unavailable.