Liu Yaowen, Yu Jingning, Hu Hao, Pu Shaoxia, Wu Haiyan, Ma Yunyu, Yang Wenhui, Fang Chongye, Sun Fei, Wang Haizhen
College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650021, China.
Department of Cardiology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming 650032, China.
Aging (Albany NY). 2025 Jun 2;17(6):1386-1404. doi: 10.18632/aging.206261.
The complex interplay between type 2 diabetes (TM) and obesity, particularly in aging populations, is increasingly recognized for its significant contribution to cardiac dysfunction. However, the metabolic changes within cardiac tissues that underlie this relationship remain poorly understood.
We employed a multi-omics approach to investigate the metabolic alterations in cardiac tissues of aging nonhuman primates with spontaneous TM and obesity. Comprehensive analysis was conducted on left ventricular heart tissues from control (CON), obesity (OB), and TM groups, each comprising three aging monkeys. Proteomic data were analyzed using label-free mass spectrometry, and lipidomic profiles were determined using targeted metabolomic assays.
Our analysis uncovered significant metabolic perturbations in both the OB and TM groups relative to controls. Notably, the TM group showed alterations in cardiac metal ion metabolic proteins and a disruption in the liver-heart crosstalk, suggesting a derailment in the heart's metabolic support system. This was further exacerbated by reduced levels of short-chain acylcarnitines and lysophosphatidylcholines (lysoPCs), coupled with an increase in C18:2 acylcarnitines. A progressive decline in amino acid levels was observed from the control to OB to TM groups, indicating a stepwise deterioration in cardiac metabolic remodeling.
This multi-omics study in aging nonhuman primates provides novel insights into the metabolic dysregulations associated with TM and obesity in cardiac tissues. The observed metabolic changes highlight potential therapeutic targets for prevention or mitigating the cardiac complications of TM.
2型糖尿病（TM）与肥胖之间复杂的相互作用，尤其是在老年人群中，因其对心脏功能障碍的重大影响而日益受到关注。然而，这种关系背后的心脏组织内代谢变化仍知之甚少。
我们采用多组学方法研究患有自发性TM和肥胖的老年非人灵长类动物心脏组织中的代谢改变。对来自对照组（CON）、肥胖组（OB）和TM组的左心室心脏组织进行了综合分析，每组包括三只老年猴子。使用无标记质谱分析蛋白质组数据，使用靶向代谢组学分析确定脂质组谱。
我们的分析发现，相对于对照组，OB组和TM组均存在显著的代谢紊乱。值得注意的是，TM组显示心脏金属离子代谢蛋白发生改变，肝心串扰中断，表明心脏代谢支持系统出现紊乱。短链酰基肉碱和溶血磷脂酰胆碱（lysoPCs）水平降低，同时C18:2酰基肉碱增加，进一步加剧了这种情况。从对照组到OB组再到TM组，氨基酸水平逐渐下降，表明心脏代谢重塑呈逐步恶化趋势。
这项针对老年非人灵长类动物的多组学研究为心脏组织中与TM和肥胖相关的代谢失调提供了新的见解。观察到的代谢变化突出了预防或减轻TM心脏并发症的潜在治疗靶点。
