Precision One Health Initiative, Department of Pathology, University of Georgia College of Veterinary Medicine, 501 D.W. Brooks Drive, Athens, GA, 30602, USA.
SMART Pharmacology, Iowa State University, Ames, IA, 50011-1250, USA.
Sci Rep. 2024 Sep 5;14(1):20665. doi: 10.1038/s41598-024-71202-y.
Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1 and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.
心血管-肾脏-代谢健康反映了代谢危险因素、慢性肾脏病和心血管系统之间的相互作用。越来越多的文献表明，正常体重人群的代谢综合征（MetS）与心血管疾病的高发率和死亡率增加有关。本研究旨在建立一种非侵入性的临床前 MetS 模型，以支持未来的研究，重点关注新型抗糖尿病疗法除了降低血糖之外对肥胖以外的影响。18 只健康成年比格犬喂食等热量的西方饮食（WD）十周。在基线（BAS1）和 WD 喂养十周后（BAS2）采集生物标本，用于测量血压（BP）、血清化学、脂蛋白谱、血糖、胰高血糖素、胰岛素分泌、NT-proBNP、血管紧张素、氧化应激生物标志物、血清、尿液和粪便代谢组学。使用非参数 Wilcoxon 符号秩检验分析 BAS1 和 BAS2 之间的差异。等热量 WD 模型诱导了 MetS 多种标志物的显著变化，包括血压升高、葡萄糖浓度升高和高密度脂蛋白胆固醇降低。它还导致循环 NT-proBNP 水平升高、血清碳酸氢盐减少以及一般代谢、脂质和生物胺发生显著变化。在犬中短期给予等热量 WD 可复制 MetS 的关键生物学特征，同时还会引起轻度代谢性酸中毒和升高利钠肽。这些发现支持使用 WD 犬模型来研究新型抗糖尿病疗法对肥胖以外的代谢影响。
