Untargeted Metabolomics Analysis Revealed Lipometabolic Disorders in Perirenal Adipose Tissue of Rabbits Subject to a High-Fat Diet.

Siqi Xia,Yanhong Li,Jie Wang,Tao Tang,Mauricio A Elzo,Yuan Ma,Tianfu Lai,Jiahao Shao,Xianbo Jia,Mingchuan Gan,Songjia Lai

doi:10.3390/ani11082289

Abstract

Simply SummaryA high-fat diet is widely recognized as a significant modifiable risk for metabolic diseases. In this study, untargeted metabolomics, combined with liquid chromatography and high-resolution mass spectrometry, was used to evaluate perirenal adipose tissue metabolic changes. Our study revealed 206 differential metabolites. These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a high-fat diet causes significant lipometabolic disorders; these metabolites may inhibit oxygen respiration by increasing adipocytes cells and density, cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thereby increasing the risk of Type 2 diabetes, atherosclerosis, and other metabolic syndromes.A high-fat diet (HFD) is widely recognized as a significant modifiable risk for insulin resistance, inflammation, Type 2 diabetes, atherosclerosis and other metabolic diseases. However, the biological mechanism responsible for key metabolic disorders in the PAT of rabbits subject to HFD remains unclear. Here, untargeted metabolomics (LC-MS/MS) combined with liquid chromatography (LC) and high-resolution mass spectrometry (MS) were used to evaluate PAT metabolic changes. Histological observations showed that the adipocytes cells and density of PAT were significantly increased in HFD rabbits. Our study revealed 206 differential metabolites (21 up-regulated and 185 down-regulated); 47 differential metabolites (13 up-regulated and 34 down-regulated), comprising mainly phospholipids, fatty acids, steroid hormones and amino acids, were chosen as potential biomarkers to help explain metabolic disorders caused by HFD. These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a HFD caused significant lipometabolic disorders. These metabolites may inhibit oxygen respiration by increasing the adipocytes cells and density, cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thus increasing the risk of Type 2 diabetes, atherosclerosis, and other metabolic syndromes.

Highlights

In recent years, the occurrence rate of obesity has fleetly increased, which poses a risk for many medical diseases, causing concern for many public and health-related professionals
The liquid chromatography (LC)-mass spectrometry (MS)/MS metabolite analyses showed that the perirenal adipose tissue (PAT) lipid cycle in in rabbits fed a high-fat diet (HFD) was disturbed, resulting in significant changes in the levels of rabbits fed a HFD was disturbed, resulting in significant changes in the levels of phosphospholipids, fatty acids, steroid hormones, and L-methionine (Figure 4C)
Histological examination and untargeted metabonomics analysis revealed that rabbits fed a HFD exhibited PAT metabolic disorders, affecting unsaturated fatty acid synthesis, and the arachidonic acid metabolic, ovarian steroidogenesis, and platelet activation pathways

Summary

Introduction

The occurrence rate of obesity has fleetly increased, which poses a risk for many medical diseases, causing concern for many public and health-related professionals. Obesity is a serious medical, social, and economic problem that has caused millions of disabilities, concomitant diseases, and deaths [1,2]. PAT is a kind of white adipose tissue that supports triglyceride (TG) storage for energy demands and endocrine function. Studies have revealed that PAT plays a significant role in controlling lipid mobilization and reproductive function as well as modulating multiple metabolic pathways [13,14]. Accumulated evidence shows that the main mechanisms leading to these metabolic diseases include endoplasmic reticulum stress and mitochondrial dysfunction [15], excessive accumulation of metabolites in adipose tissue, imbalance of energy supply and metabolic homeostasis [16], reduction of reverse cholesterol transport [17], aggravation of inflammation and reduction of insulin sensitivity [18]. One of the most significant and destructive complications is abnormal lipid metabolism, which will definitely worsen in the future [19]

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Discussion

Conclusion