Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2024; 15(5): 988-1000
Published online May 15, 2024. doi: 10.4239/wjd.v15.i5.988
Estrogen restores disordered lipid metabolism in visceral fat of prediabetic mice
Su-Huan Liu, Zhao-Shui Shangguan, Paiziliya Maitiaximu, Zhi-Peng Li, Xin-Xin Chen, Can-Dong Li
Su-Huan Liu, Can-Dong Li, Research Base of Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China
Su-Huan Liu, Zhao-Shui Shangguan, Paiziliya Maitiaximu, Zhi-Peng Li, Xin-Xin Chen, Research Center for Translational Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, Fujian Province, China
Co-first authors: Su-Huan Liu and Zhao-Shui Shangguan.
Author contributions: Liu SH was responsible for conceptualization, data collection and analysis, draft preparation, and funding acquisition; Shangguan ZS, Maitiaximu P, Li ZP, and Chen XX were responsible for data collection and analysis; Li CD was responsible for supervision and reviewing. Liu SH and Shangguan ZS contributed equally to this work as co-first authors. The reason for designating Liu SH and Shangguan ZS as co-first authors is because the research was performed as a collaborative effort, to which Liu SH and Shangguan ZS contributed efforts of equal substance throughout the research process.
Supported by National Natural Science Foundation of China, No. 81270901 and No. 81970672.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Xiamen University (Approval No. XMULAC20190105).
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Data sharing statement: Materials, data, and associated protocols will be promptly available upon request.
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: Can-Dong Li, MD, PhD, Chief Doctor, President, Professor, Research Base of Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, No. 1 Qiuyang Road, Fuzhou 350122, China. fjzylcd@126.com
Received: December 31, 2023
Peer-review started: December 31, 2023
First decision: January 17, 2024
Revised: January 26, 2024
Accepted: March 11, 2024
Article in press: March 11, 2024
Published online: May 15, 2024
Processing time: 131 Days and 6.4 Hours
Abstract
BACKGROUND

Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes. Estrogen [17β-estradiol (E2)] is known to offer protection against obesity via diverse me-chanisms, while its specific effects on visceral adipose tissue (VAT) remain to be fully elucidated.

AIM

To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.

METHODS

Metabolic parameters were collected, encompassing body weight, weights of visceral and subcutaneous adipose tissues (VAT and SAT), random blood glucose levels, glucose tolerance, insulin tolerance, and overall body composition. The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software. Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively.

RESULTS

Feeding a high-fat diet (HFD) moderately increased the weights of both VAT and SAT, but this increase was mitigated by the protective effect of endogenous E2. Conversely, ovariectomy (OVX) led to a significant increase in VAT weight and the VAT/SAT weight ratio, and this increase was also reversed with E2 treatment. Notably, OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone, signaling a widespread reduction in lipid metabolic activity, which was completely counteracted by E2 administration. This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.

CONCLUSION

In conclusion, the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat, leading to a universally decreased lipid metabolic status in E2 deficient mice. E2 treatment effectively reversed this condition, shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.

Keywords: Estrogen; Obesity, Visceral adiposity; Energy metabolism; Type 2 diabetes

Core Tip: It is widely accepted that adipocyte hypertrophy arises from an increase in lipogenesis and/or a reduction in lipolysis. Our findings reveal that despite the presence of adipocyte hypertrophy and visceral adiposity, the expression of genes related to both fatty acid biosynthesis and oxidation in visceral adipose tissue was significantly reduced following ovariectomy (OVX) in mice fed a high-fat diet, suggesting a comprehensive decline in metabolic activity. Remarkably, estrogen treatment fully reversed the disrupted expression patterns of lipid metabolic genes in OVX mice, correcting their disordered metabolic phenotype. This study unveils a novel mechanism underlying visceral adiposity and highlights estrogen's protective role against visceral obesity.