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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Vydané v:	Scientific reports Ročník 14; číslo 1; s. 9820 - 11
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 29.04.2024 Nature Publishing Group Nature Portfolio
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-60365-3