The soluble (Pro) renin receptor does not influence lithium‐induced diabetes insipidus but does provoke beiging of white adipose tissue in mice

Abstract

Earlier we reported that the recombinant soluble (pro) renin receptor sPRR‐His upregulates renal aquoporin‐2 (AQP2) expression, and attenuates polyuria associated with nephrogenic diabetes insipidus (NDI) induced by vasopressin type 2 receptor (V2R) antagonism. Patients that receive lithium therapy develop polyuria associated NDI that might be secondary to downregulation of renal AQP2. We hypothesized that sPRR‐His attenuates indices of NDI associated with lithium treatment. Eight‐week‐old male C57/BL6 mice consumed chow supplemented with LiCl (40 mmol/kg diets) for 14 days. For the last 7 days mice received either sPRR‐His [30 μg/(kg day), i.v.; sPRR] or vehicle (Veh) via minipump. Control (Con) mice consumed standard chow for 14 days. Compared to Con mice, 14‐d LiCl treatment elevated water intake and urine volume, and decreased urine osmolality, regardless of sPRR‐His or Veh administration. These data indicate that sPRR‐His treatment does not attenuate indices of NDI evoked by lithium. Unexpectedly, epididymal fat mass was lower, adipocyte UCP1 mRNA and protein expression were higher, and multilocular lipid morphology was enhanced, in LiCl‐fed mice treated with sPRR‐His versus vehicle. The beiging of white adipose tissue is a novel metabolic benefit of manipulating the sPRR in the context of lithium‐induced NDI.

Site-1 Protease-Derived Soluble (Pro)Renin Receptor Contributes to Angiotensin II–Induced Hypertension in Mice

“…Recently, a series of studies from our group and others have begun to unravel the biological function of sPRR 32 , 33 as well as identity of the cleavage proteases. 5 , 6 The present study is the first to show that S1P-derived sPRR contributes to Ang II–induced hypertension.…”

Angiotensin receptor subtypes regulate adipose tissue renewal and remodelling

“…Although PRR activates the intracellular ERK1/2 signalling cascade [47], its role in the regulation of adiposity is instead attributed to enhanced processing of Agt into AngI and not by specific signalling triggered by this receptor [46]. Recent data suggest that soluble PRR induces beiging of WAT in mice, but the mechanism is not yet known [48]. Altogether, these data highlight the importance of pericellular Agt conversion in the regulation of adipose tissue expansion.…”

Soluble (pro)renin receptor treats metabolic syndrome in mice with diet-induced obesity via interaction with PPARγ

“…receptor antagonism (17). Although sPRR-His is ineffective in treating lithium-induced diabetes insipidus, it reduces the epididymal fat mass by enhancing the "beiging" process, indicating a possible role of sPRR in the regulation of adipocyte biology during lithium overload (18). The goal of the present study was to perform a vigorous evaluation of sPRR-His as a potential therapy for metabolic diseases, such as obesity and associated conditions, and to further explore the underlying mechanism.…”