Lysine Deprivation Suppresses Adipogenesis in 3T3-L1 Cells: A Transcriptome Analysis
-
Published:2023-05-28
Issue:11
Volume:24
Page:9402
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Lee Leo Man-Yuen123ORCID, Lin Zhi-Qiang3ORCID, Zheng Lu-Xi3, Tu Yi-Fan124, So Yik-Hing12, Zheng Xiu-Hua3, Feng Tie-Jun3, Wang Xi-Yue5ORCID, Wong Wai-Ting1, Leung Yun-Chung12ORCID
Affiliation:
1. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China 2. Lo Ka Chung Research Centre for Natural Anti-Cancer Drug Development and State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China 3. School of Biomedical Science, The Chinese University of Hong Kong, Shatin, New Territory, Hong Kong, China 4. Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, New Territory, Hong Kong, China 5. Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518000, China
Abstract
Growing evidence proves that amino acid restriction can reverse obesity by reducing adipose tissue mass. Amino acids are not only the building blocks of proteins but also serve as signaling molecules in multiple biological pathways. The study of adipocytes’ response to amino acid level changes is crucial. It has been reported that a low concentration of lysine suppresses lipid accumulation and transcription of several adipogenic genes in 3T3-L1 preadipocytes. However, the detailed lysine-deprivation-induced cellular transcriptomic changes and the altered pathways have yet to be fully studied. Here, using 3T3-L1 cells, we performed RNA sequencing on undifferentiated and differentiated cells, and differentiated cells under a lysine-free environment, and the data were subjected to KEGG enrichment. We found that the differentiation process of 3T3-L1 cells to adipocytes required the large-scale upregulation of metabolic pathways, mainly on the mitochondrial TCA cycle, oxidative phosphorylation, and downregulation of the lysosomal pathway. Single amino acid lysine depletion suppressed differentiation dose dependently. It disrupted the metabolism of cellular amino acids, which could be partially reflected in the changes in amino acid levels in the culture medium. It inhibited the mitochondria respiratory chain and upregulated the lysosomal pathway, which are essential for adipocyte differentiation. We also noticed that cellular interleukin 6 (IL6) expression and medium IL6 level were dramatically increased, which was one of the targets for suppressing adipogenesis induced by lysine depletion. Moreover, we showed that the depletion of some essential amino acids such as methionine and cystine could induce similar phenomena. This suggests that individual amino acid deprivation may share some common pathways. This descriptive study dissects the pathways for adipogenesis and how the cellular transcriptome was altered under lysine depletion.
Funder
Start-up Fund for RAPs
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference58 articles.
1. World Health Organization (2021). Obesity and Overweight Fact Sheets, World Health Organization. 2. Medicalizing Obesity: Individual, Economic, and Medical Consequences;Blackburn;AMA J. Ethics,2011 3. Impacts of essential amino acids on energy balance;Xiao;Mol. Metab.,2022 4. Dietary Protein and Energy Balance in Relation to Obesity and Co-morbidities;Drummen;Front. Endocrinol.,2018 5. Ferraz-Bannitz, R., Beraldo, R.A., Peluso, A.A., Dall, M., Babaei, P., Foglietti, R.C., Martins, L.M., Gomes, P.M., Marchini, J.S., and Suen, V.M.M. (2022). Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial. Nutrients, 14.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|