Abstract
Kidney disease occurs in approximately 15% of the adult population, accounting for 37 million people in the US alone. Lack of blood flow is a major driver of kidney injury and no therapeutic modalities have shown substantial effcacy in treating ischemia-induced acute kidney injury (AKI). We recently demonstrated that activation of the brain leptin-melanocortin system dramatically improves cardiomyocyte mitochondrial function, energy metabolism and contractility, preserving cardiac function and preventing progression of heart failure following myocardial infarction and ischemia/reperfusion injury. In the present study we examined whether chronic intracerebroventricular (ICV) leptin administration protects the kidney against ischemia/reperfusion (I/R)-induced AKI. Twelve-week old male rats were implanted with an ICV cannula into the right lateral ventricle and 8-10 days after surgery, leptin (0.021 mg/hr, n=8) or saline vehicle (0.5 ml/h, n=8) was infused via osmotic minipump connected to the ICV cannula for 12 days. On day 8 of leptin or vehicle infusion, rats were submitted to unilateral ischemia/reperfusion (UIR) by clamping the left pedicle for 30 min. To control for leptin-induced reductions in food intake, the vehicle group was pair-fed (UIR-PF) to match the same amount of food consumed by leptin-treated (UIR-Leptin) rats. On the 12th day of leptin or vehicle infusion (i.e. 4th day after AKI), single-left kidney glomerular filtration rate (GFR) was measured, blood samples were collected to quantify white blood cells, and kidneys were collected for histological assessment of injury. Chronic leptin infusion reduced body weight by 20±1% compared to only 10±1% reduction in UIR-PF. UIR-Leptin rats also showed reduced right and left kidney weights (right: 1040±24 vs. 1281±36 and left: 1127±71 vs. 1707±45 mg, for UIR-Leptin and UIR-PF, respectively). Leptin infusion improved GFR (0.50±0.06 vs. 0.13±0.03 ml/min/g KW) and reduced kidney injury scores. Leptin treatment also increased circulating white blood cells count compared to UIR-PF rats (16.3±1.3 vs. 9.8±0.6 k/mL). Thus, leptin, via its actions on the central nervous system, confers significant protection against major kidney dysfunction and damage in a model of ischemia/reperfusion-induced AKI. NIH grants: (1R0DK1121411 (do Carmo), 1R0HL1630376 (da Silva/do Carmo), P20GM104357 (Hall), P30GM149404 (Hall) and U54GM115428 (Hall)). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
