The role and regulation of FOXO1 in carbohydrate metabolism and its targeting in metabolic diseases
DOI:
https://doi.org/10.55392/indarcbiores.v1i2.8Keywords:
FOXO1, gluconeogenesis, metabolic disease, protein processing, post-translationalAbstract
Carbohydrate is the first energy source used in metabolic processes. Failure in carbohydrate metabolism can cause metabolic diseases, and many studies are focused on its therapy. Until now, there is no specific therapy approved. Despite that, one of the main alternatives is regarding the involvement of FOXO1 protein in metabolic disease progress. As a transcription factor for gluconeogenesis genes, FOXO1 can increase blood glucose levels. It also involves various signaling pathways in carbohydrate metabolisms such as PI3K/Akt and PKA in which many proteins act as FOXO1 regulators through posttranslational modification. The vital role of FOXO1 in carbohydrate metabolism provides an opportunity to make FOXO1 the main target of metabolic disease therapy. Various proteins and natural compounds can either directly or indirectly regulate FOXO1 activity. It can be an option to be used to control blood glucose levels by targeting FOXO1
Downloads
References
World Health Organization. Classification of Diabetes Mellitus. Geneva: World Health Organization; 2019. 6 p.
Gu L, Ding X, Wang Y, Gu M, Zhang J, Yan S, et al. Spexin alleviates insulin resistance and inhibits hepatic gluconeogenesis via the FoxO1/PGC-1 α pathway in high-fat-diet-induced rats and insulin resistant cells. Int J Biol Sci. 2019;15(13):2815–29. https://www.ncbi.nlm.nih.gov › articles › PMC6909969
Wu Y, Pan Q, Yan H, Zhang K, Guo X, Xu Z, et al. Novel Mechanism of Foxo1 Phosphorylation in Glucagon Signaling in Control of Glucose Homeostasis. Diabetes. 2018;67(11):2167–82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198346/
Kodani N, Nakae J. Tissue-Specific Metabolic Regulation of FOXO-Binding Protein: FOXO Does Not Act Alone. Cells. 2020;9(3):702. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140670/
Jiang Y, Yan F, Feng Z, Lazarovici P, Zheng W. Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction. Cells. 2020;9:100. https://pubmed.ncbi.nlm.nih.gov/31906091/
Chen J, Lu Y, Tian M, Huang Q. Molecular mechanisms of FOXO1 in adipocyte differentiation. J Mol Endocrinol. 2019;62(3):R239-53. https://jme.bioscientifica.com/view/journals/jme/62/3/JME-18-0178.xml
Langlet F, Haeusler RA, Lindén D, Ericson E, Norris T, Johansson A, et al. Selective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic Glucose Handling. Cell. 2017;171(4). https://pubmed.ncbi.nlm.nih.gov/29056338/
Li Y, Ma Z, Jiang S, Hu W, Li T, Di S, et al. A global perspective on FOXO1 in lipid metabolism and lipid-related diseases. Prog Lipid Res. 2017;66:42–9. https://pubmed.ncbi.nlm.nih.gov/28392404/
Park J, Hwang I, Kim SJ, Youn SW, Hur J, Kim HS. Atorvastatin prevents endothelial dysfunction in high glucose condition through Skp2-mediated degradation of FOXO1 and ICAM-1. Biochem Biophys Res Commun. 2018;495(2):2050–7. https://pubmed.ncbi.nlm.nih.gov/28802579/
Li K, Qiu C, Sun P, Chen F, Li K, Qiu C, et al. Ets1-Mediated Acetylation of FoxO1 Is Critical for Gluconeogenesis Regulation during Feed-Fast Article Ets1-Mediated Acetylation of FoxO1 Is Critical for Gluconeogenesis Regulation during Feed-Fast Cycles. Cell Rep. 2019;26(11):2998-3010.e5. https://pubmed.ncbi.nlm.nih.gov/30865889/
Chae Y, Kim J, Park JW, Kim K, Oh H, Lee K, et al. FOXO1 degradation via G9a-mediated methylation promotes cell proliferation in colon cancer. Nucleic Acid Res. 2019;47(4):1692–705. https://pubmed.ncbi.nlm.nih.gov/30535125/
Jiang Z, Xing B, Feng Z, Ma J, Ma X, Hua X. Menin Upregulates FOXO1 Protein Stability by Repressing Skp2-Mediated Degradation in β Cells. Pancreas. 2019;48(2):267–74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336489/
Youse E, Saboori S, Djalali M, Falahi E, Gholamhosseini S, Nematipour E. Omega-3 fatty acids and vitamin E supplementation can affect gene expressions of SIRT1, FOXO1 and UCP-2 in coronary artery disease patients. Obes Med. 2019;15. https://pubmed.ncbi.nlm.nih.gov/27033026/
Kodani N, Nakae J, Kobayashi M, Kikuchi O, Kitamura T, Itoh H. FCoR-Foxo1 Axis Regulates α-Cell Mass through Repression of Arx Expression. iScience. 2020;23(1). https://pubmed.ncbi.nlm.nih.gov/31923647/
Peng S, Xiao W, Ju D, Sun B, Hou N, Liu Q, et al. Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1. Sci Transl Med. 2019;11:1–12. https://pubmed.ncbi.nlm.nih.gov/30996080/
Santoleri D, Titchenell PM. Resolving the Paradox of Hepatic Insulin Resistance. Cell Mol Gastroenterol Hepatol. 2019;7(2):447–56. https://pubmed.ncbi.nlm.nih.gov/30739869/
Yan H, Yang W, Zhou F, Li X, Pan Q, Shen Z, et al. Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1. Diabetes. 2019;68:291–304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341301/
Gao J, He X, Ma Y, Zhao X, Hou X, Hao E, et al. Chlorogenic Acid Targeting of the AKT PH Domain Activates AKT-GSK3β-FOXO1 Signaling and Improves Glucose Metabolism. Nutrients. 2018;10(1366):1–13. https://pubmed.ncbi.nlm.nih.gov/30249058/
Zhang J, Chen Y, Liu C, Li L, Li P. N1-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation. J Diabetes Res. 2020;2020:1–11. https://pubmed.ncbi.nlm.nih.gov/32280711/
Zhang L, Yao W, Xia J, Wang T, Huang F. Glucagon-Induced Acetylation of Energy-Sensing Factors in Control of Hepatic Metabolism. Int J Mol Sci. 2019;20(8):1885. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515121/
Rudnicki M, Abdifarkosh G, Nwadozi E, Ramos S V., Makki A, Sepa-Kishi DM, et al. Endothelial-specific FoxO1 depletion prevents obesity-related disorders by increasing vascular metabolism and growth. Elife. 2018;7:e39780. https://pubmed.ncbi.nlm.nih.gov/30511639/
Li Y, Pan H, Zhang X, Wang H, Liu S, Zhang H, et al. Geniposide Improves Glucose Homeostasis via Regulating FoxO1/PDK4 in Skeletal Muscle. J Agric Food Chem. 2019;67(16):4483–92. https://pubmed.ncbi.nlm.nih.gov/30929433/
Carling D. AMPK signalling in health and disease. Curr Opin Cell Biol. 2017;45:31–7. https://pubmed.ncbi.nlm.nih.gov/28232179/
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2021 Indonesian Archives of Biomedical Research

This work is licensed under a Creative Commons Attribution 4.0 International License.