Jussara M do Carmo, John E Hall, Xuemei Dai, Nikaela Aitkens, Kylie Larson, Emilio M Luna-Suarez, Zhen Wang, Ana C M Omoto, Alan Mouton, Xuan Li, Luzia N S Furukawa, Viktoria Woronik, Alexandre A da Silva
{"title":"Parental obesity predisposes offspring to kidney dysfunction and increased susceptibility to ischemia-reperfusion injury in a sex-dependent manner.","authors":"Jussara M do Carmo, John E Hall, Xuemei Dai, Nikaela Aitkens, Kylie Larson, Emilio M Luna-Suarez, Zhen Wang, Ana C M Omoto, Alan Mouton, Xuan Li, Luzia N S Furukawa, Viktoria Woronik, Alexandre A da Silva","doi":"10.1152/ajprenal.00294.2023","DOIUrl":null,"url":null,"abstract":"<p><p>Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.<b>NEW & NOTEWORTHY</b> Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386979/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Renal physiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1152/ajprenal.00294.2023","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/21 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.
虽然肥胖被认为是心肾疾病和代谢性疾病的危险因素,但父母肥胖对其后代成年后肾损伤易感性的影响尚不清楚。我们研究了父母肥胖对后代肾功能、形态以及急性肾损伤(AKI)后肾损伤标志物的影响。从断奶到成年,喂养正常(N)饮食的 C57BL/6J 亲本的后代要么喂养 N(NN)饮食,要么喂养高脂肪(H)饮食(NH)。肥胖的 H 型饮食喂养亲本的后代断奶后喂养 N 型饮食(HN)或 H 型饮食(HH)。通过夹闭左右肾蒂 30 分钟,对所有子代组进行双侧肾动脉缺血。与来自瘦父母的NH和NN雄性后代相比,来自肥胖父母的HH和HN雄性后代在22周龄时表现出更高的肾损伤指标,如尿、肾骨蛋白、血浆肌酐、尿白蛋白排泄量和NGAL水平,以及更差的组织学损伤评分。与瘦父母和肥父母的肥胖后代相比,肥父母的肥胖后代中只有白蛋白排泄量和NGAL水平升高。我们还发现,无论断奶后的饮食如何,肥胖父母所生的雄性后代的死亡率增加,肾脏损伤评分也更差。而雌性后代在发生 AKI 后则不会出现严重的肾损伤。这些结果表明,父母肥胖会以性别依赖的方式导致其后代在缺血/再灌注后肾脏损伤加重,即使其后代仍然很瘦。