Obesity aggravates acute kidney injury resulting from ischemia and reperfusion in mice

In critically ill patients, overweight and obesity are associated with acute respiratory distress syndrome and acute kidney injury (AKI). However, the effect of obesity on ischemia–reperfusion injury (IRI)-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice. We fed...

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Published in:Scientific reports Vol. 14; no. 1; pp. 9820 - 11
Main Authors: da Silva, Igor Oliveira, de Menezes, Nicole K., Jacobina, Heloisa D., Parra, Antonio Carlos, Souza, Felipe Lima, Castro, Leticia Cardoso, Roelofs, Joris J. T. H., Tammaro, Alessandra, Gomes, Samirah Abreu, Sanches, Talita Rojas, Andrade, Lucia
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 29.04.2024
Nature Publishing Group
Nature Portfolio
Subjects:
631/443/272
631/443/319/2723
Acute Kidney Injury - etiology
Acute Kidney Injury - metabolism
Acute Kidney Injury - pathology
Animals
Caspase-3
Cholesterol
Creatinine
Diet, High-Fat - adverse effects
Disease Models, Animal
Ferroptosis
Gelatinase
Glucuronidase - metabolism
Glutathione peroxidase
Heme oxygenase (decyclizing)
High fat diet
Humanities and Social Sciences
Ischemia
Kidney - metabolism
Kidney - pathology
Kidneys
Klotho protein
Leukocytes (neutrophilic)
Lipid peroxidation
Lipocalin
Macrophages
Male
Mice
Mice, Inbred C57BL
multidisciplinary
Obesity
Obesity - complications
Obesity - metabolism
Oxidative Stress
Peroxidation
Peroxiredoxin
Proliferating cell nuclear antigen
Protein expression
Reperfusion
Reperfusion Injury - complications
Reperfusion Injury - metabolism
Reperfusion Injury - pathology
Respiratory distress syndrome
Science
Science (multidisciplinary)
Therapeutic targets
Thiobarbituric acid
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:In critically ill patients, overweight and obesity are associated with acute respiratory distress syndrome and acute kidney injury (AKI). However, the effect of obesity on ischemia–reperfusion injury (IRI)-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice. We fed mice a standard or high-fat diet for eight weeks. The mice were divided into four groups and submitted to sham surgery or IRI: obese, normal, normal + IRI, obese, and obese + IRI. All studies were performed 48 h after the procedures. Serum glucose, cholesterol, and creatinine clearance did not differ among the groups. Survival and urinary osmolality were lower in the obese + IRI group than in the normal + IRI group, whereas urinary neutrophil gelatinase-associated lipocalin levels, tubular injury scores, and caspase 3 expression were higher. Proliferating cell nuclear antigen expression was highest in the obese + IRI group, as were the levels of oxidative stress (urinary levels of thiobarbituric acid-reactive substances and renal heme oxygenase-1 protein expression), whereas renal Klotho protein expression was lowest in that group. Expression of glutathione peroxidase 4 and peroxiredoxin 6, proteins that induce lipid peroxidation, a hallmark of ferroptosis, was lower in the obese + IRI group. Notably, among the mice not induced to AKI, macrophage infiltration was greater in the obese group. In conclusion, greater oxidative stress and ferroptosis might aggravate IRI in obese individuals, and Klotho could be a therapeutic target in those with AKI.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-60365-3