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FGF21 increases water intake, urine output and blood pressure in rats.

ABSTRACT: Fibroblast growth factor 21 (FGF21) is a hormone secreted by the liver in response to metabolic stress. In addition to its well-characterized effects on energy homeostasis, FGF21 has been shown to increase water intake in animals. In this study, we sought to further explore the effects of FGF21 on fluid homeostasis in rats. A single dose of a long-acting FGF21 analog, PF-05231023, significantly increased water consumption, which was accompanied by an elevation in urine output that appeared prior to a significant change in water intake. We observed that FGF21 rapidly and significantly increased heart rate and blood pressure in telemeter-implanted rats, before changes in urine output and water intake were observed. Our data suggest that sympathetic activation may contribute to the pathogenesis by which FGF21 increases blood pressure as the baroreceptor unloading induced reflex tachycardia was significantly elevated in FGF21-treated animals. However, FGF21 was still capable of causing hypertension in animals in which approximately 40% of the sympathetic post-ganglionic neurons were ablated. Our data suggest that FGF21-induced water intake is in fact secondary to diuresis, which we propose to be a compensatory mechanism engaged to alleviate the acute hypertension caused by FGF21.

SUBMITTER: Turner T

PROVIDER: S-EPMC6091943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. METHODS:This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. RESULTS:In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98-0.99, P?=?0.002) and as a quartile variable (OR of Q2 to Q4: 0.69-0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ?0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03-0.253, P?<? 0.001); this association was not significant for patients with UO/FI ratios >?0.5 (OR: 1.04, 95% CI: 0.96-1.14, P?=?0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ?0.5 (OR: 0.97, 95% CI: 0.96-0.99, P?=?0.006), but not in the subgroup with a UO/FI >?0.5. CONCLUSIONS:The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

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FGF21 increases water intake, urine output and blood pressure in rats.

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