Research Paper|Volume 17, Issue 6|pp 1386—1404

Multi-omics analysis reveals metabolic disruptions in cardiac tissues of aging nonhuman primates with spontaneous type 2 diabetes

Yaowen Liu¹, Jingning Yu¹, Hao Hu¹, Shaoxia Pu¹, Haiyan Wu³, Yunyu Ma⁴, Wenhui Yang⁴, Chongye Fang², Fei Sun¹, Haizhen Wang¹

¹College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650021, China
²College of Food Science and Technology, Yunnan Agricultural University, Kunming 650021, China
³Department of Cardiology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming 650032, China
⁴Department of Cardiology, Fuwai Yunnan Cardiovascular Hospital, Kunming 650102, China

* Equal contribution

Received: December 2, 2024Accepted: April 8, 2025Published: June 2, 2025

https://doi.org/10.18632/aging.206261

Copyright: © 2025 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.