Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2022; 13(11): 972-985
Published online Nov 15, 2022. doi: 10.4239/wjd.v13.i11.972
Dietary Nε-(carboxymethyl) lysine affects cardiac glucose metabolism and myocardial remodeling in mice
Zhong-Qun Wang, Zhen Sun
Zhong-Qun Wang, Zhen Sun, Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
Author contributions: Sun Z designed the study and wrote the manuscript; Wang ZQ performed the experiments, analyzed the data, and prepared the images; all authors edited and approved the final version of the article.
Supported by the National Natural Science Foundation of China, No. 82070455; Natural Science Foundation of Jiangsu Province, No. BK20201225; Medical Innovation Team Project of Jiangsu Province, No. CXTDA2017010; and Research and Innovation Funding Project for College Students in Experimental Animal Center of Jiangsu University.
Institutional animal care and use committee statement: All animal experiments were approved by the Experimental Animal Use Ethics Committee of Jiangsu University.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhen Sun, PhD, Doctor, Department of Cardiology, Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang 212001, Jiangsu Province, China. 1398041019@qq.com
Received: August 16, 2022
Peer-review started: August 16, 2022
First decision: September 4, 2022
Revised: September 15, 2022
Accepted: October 11, 2022
Article in press: October 11, 2022
Published online: November 15, 2022
Processing time: 87 Days and 8.5 Hours
Abstract
BACKGROUND

Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage. In addition to myocardial infarction or stress overload, dietary factors have recently been considered associated with myocardial remodeling. Nε-(carboxymethyl)lysine (CML) is a representative foodborne toxic product, which can be ingested via daily diet. Therefore, there is a marked need to explore the effects of dietary CML on the myocardium.

AIM

To explore the effects of dietary CML (dCML) on the heart.

METHODS

C57 BL/6 mice were divided into a control group and a dCML group. The control group and the dCML group were respectively fed a normal diet or diet supplemented with CML for 20 wk. Body weight and blood glucose were recorded every 4 wk. 18F-fluorodeoxyglucose (FDG) was used to trace the glucose uptake in mouse myocardium, followed by visualizing with micro-positron emission tomography (PET). Myocardial remodeling and glucose metabolism were also detected. In vitro, H9C2 cardiomyocytes were added to exogenous CML and cultured for 24 h. The effects of exogenous CML on glucose metabolism, collagen I expression, hypertrophy, and apoptosis of cardiomyocytes were analyzed.

RESULTS

Our results suggest that the levels of fasting blood glucose, fasting insulin, and serum CML were significantly increased after 20 wk of dCML. Micro-PET showed that 18F-FDG accumulated more in the myocardium of the dCML group than in the control group. Histological staining revealed that dCML could lead to myocardial fibrosis and hypertrophy. The indexes of myocardial fibrosis, apoptosis, and hypertrophy were also increased in the dCML group, whereas the activities of glucose metabolism-related pathways and citrate synthase (CS) were significantly inhibited. In cardiomyocytes, collagen I expression and cellular size were significantly increased after the addition of exogenous CML. CML significantly promoted cellular hypertrophy and apoptosis, while pathways involved in glucose metabolism and level of Cs mRNA were significantly inhibited.

CONCLUSION

This study reveals that dCML alters myocardial glucose metabolism and promotes myocardial remodeling.

Keywords: Diet; Myocardial remodeling; Glucose metabolism; Nε-(carboxymethyl)lysine; C57 BL/6 mice

Core Tip: Nε-(carboxymethyl)lysine (CML) exists in daily diet and is harmful to health. We established in vitro and in vivo models to investigate the effects of dietary CML (dCML) on the heart. We found that long-term dCML induced insulin resistance and elevated serum CML level. 18F-fluorodeoxyglucose imaging indicated that dCML promoted myocardial glucose uptake, but the glucose metabolism was disrupted. Myocardial fibrosis, apoptosis, and hypertrophy were significantly enhanced by dCML. In the cell model, CML supplementation promoted cardiomyocyte apoptosis, cellular hypertrophy, and collagen I expression, and also inhibited pathways involved in glucose metabolism.