Reduced Expression of Twist 1 is Protective Against Insulin Resistance of Adipocytes and Involves Mitochondrial Dysfunction

Overview

Journal Sci Rep

Specialty Science

Date 2018 Aug 24

PMID 30135600

Citations 8

Authors

Sumei Lu

Hong Wang

Rui Ren

Xiaohong Shi

Yanmei Zhang

Wanshan Ma

Affiliations

Soon will be listed here.

Abstract

Insulin resistance (IR) has become a global epidemic that represents a serious hazard to public health. However, the precise mechanisms modulating IR have not been fully elucidated. The present study aimed to investigate the role of transcriptional factor Twist 1 in adipocyte IR and to further explore the molecular mechanism. An in vitro IR model based on cultured 3T3-L1 adipocytes was established under high glucose/insulin stimulation and an in vivo IR model in C57/BL6J mice induced by a high fat diet (HFD) was also developed. Lentivirus targeting Twist 1 silencing was introduced. The relationships between Twist 1 expression and IR state, mitochondrial dysfunction and the downstream insulin signaling pathway were assayed. Our results firstly showed the elevation of Twist 1 in IR adipocytes, and Twist 1 silencing attenuated IR. Then mitochondrial ultra-structural damage, elevated ROS, decreased MMP and ATP, and changes in mitochondrial biosynthesis-related genes in IR group indicated mitochondrial dysfunction. Further, the downstream IRS/PI3K/AKT/GluT4 pathway was showed involved in Twist 1-mediated IR. In total, we provide evidence of a protective role of Twist 1 silencing in relieving the IR state of adipocytes. Mitochondrial dysfunction and the downstream IRS/PI3K/AKT/GluT4 pathway were involved in this Twist 1-mediated IR.

Citing Articles

Roles of Twist1 in lipid and glucose metabolism.

Huang L, Xing Y, Ning X, Yu Z, Bai X, Liu L Cell Commun Signal. 2023; 21(1):270.

PMID: 37784111 PMC: 10544448. DOI: 10.1186/s12964-023-01262-6.

METTL3 exacerbates insulin resistance in hepatocytes by regulating mA modification of cytochrome P450 2B6.

Li Y, Zhang D, Gao Y, Wang P, Wang Z, Zhang B Nutr Metab (Lond). 2023; 20(1):40.

PMID: 37710320 PMC: 10502999. DOI: 10.1186/s12986-023-00762-z.

The HDAC9-associated risk locus promotes coronary artery disease by governing TWIST1.

Ma L, Bryce N, Turner A, Di Narzo A, Rahman K, Xu Y PLoS Genet. 2022; 18(6):e1010261.

PMID: 35714152 PMC: 9246173. DOI: 10.1371/journal.pgen.1010261.

Twist1 downregulation of PGC-1α decreases fatty acid oxidation in tubular epithelial cells, leading to kidney fibrosis.

Liu L, Ning X, Wei L, Zhou Y, Zhao L, Ma F Theranostics. 2022; 12(8):3758-3775.

PMID: 35664054 PMC: 9131259. DOI: 10.7150/thno.71722.

Epithelial mesenchymal transition regulator TWIST1 transcription factor stimulates glucose uptake through upregulation of GLUT1, GLUT3, and GLUT12 in vitro.

Pehlivanoglu S, Sahan O, Pehlivanoglu S, Aktas Kont K In Vitro Cell Dev Biol Anim. 2021; 57(10):933-943.

PMID: 34791627 DOI: 10.1007/s11626-021-00635-w.

References

Okamoto M, Yamaoka M, Takei M, Ando T, Taniguchi S, Ishii I . Endogenous hydrogen sulfide protects pancreatic beta-cells from a high-fat diet-induced glucotoxicity and prevents the development of type 2 diabetes. Biochem Biophys Res Commun. 2013; 442(3-4):227-33. DOI: 10.1016/j.bbrc.2013.11.023. View

Kim B, Sohn E, Jung J, Shin E, You O, Im J . Inhibition of ZNF746 suppresses invasion and epithelial to mesenchymal transition in H460 non-small cell lung cancer cells. Oncol Rep. 2013; 31(1):73-8. DOI: 10.3892/or.2013.2801. View

Diop S, Bisharat-Kernizan J, Birse R, Oldham S, Ocorr K, Bodmer R . PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity Downstream of TOR and Brummer ATGL Lipase. Cell Rep. 2015; 10(9):1572-1584. PMC: 4560688. DOI: 10.1016/j.celrep.2015.02.022. View

Battula V, Evans K, Hollier B, Shi Y, Marini F, Ayyanan A . Epithelial-mesenchymal transition-derived cells exhibit multilineage differentiation potential similar to mesenchymal stem cells. Stem Cells. 2010; 28(8):1435-45. PMC: 3523728. DOI: 10.1002/stem.467. View

Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S . MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1/AMPK pathway. Circ Res. 2014; 116(2):279-88. DOI: 10.1161/CIRCRESAHA.116.304707. View

Ren R, Chen Z, Zhao X, Sun T, Zhang Y, Chen J . A possible regulatory link between Twist 1 and PPARγ gene regulation in 3T3-L1 adipocytes. Lipids Health Dis. 2016; 15(1):189. PMC: 5101646. DOI: 10.1186/s12944-016-0361-x. View

Montgomery M, Turner N . Mitochondrial dysfunction and insulin resistance: an update. Endocr Connect. 2014; 4(1):R1-R15. PMC: 4261703. DOI: 10.1530/EC-14-0092. View

Zhou X, Zhu J, Bao Z, Shang Z, Wang T, Song J . A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients. Sci Rep. 2016; 6:37293. PMC: 5114551. DOI: 10.1038/srep37293. View

Jabri M, Sakly M, Marzouki L, Sebai H . Chamomile (Matricaria recutita L.) decoction extract inhibits in vitro intestinal glucose absorption and attenuates high fat diet-induced lipotoxicity and oxidative stress. Biomed Pharmacother. 2017; 87:153-159. DOI: 10.1016/j.biopha.2016.12.043. View

10.

Qi S, He Z, Chen Y, Ma J, Yu W, Li Y . Relevance and clinical significance of serum resistin level in obese T2DM rhesus monkey models. Exp Clin Endocrinol Diabetes. 2015; 123(8):508-13. DOI: 10.1055/s-0035-1554653. View

11.

Chennamsetty I, Coronado M, Contrepois K, Keller M, Carcamo-Orive I, Sandin J . Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice. Cell Rep. 2016; 17(2):527-540. PMC: 5097870. DOI: 10.1016/j.celrep.2016.09.005. View

12.

Muniyappa R, Yavuz S . Metabolic actions of angiotensin II and insulin: a microvascular endothelial balancing act. Mol Cell Endocrinol. 2012; 378(1-2):59-69. PMC: 3478427. DOI: 10.1016/j.mce.2012.05.017. View

13.

Valenzuela R, Barrera C, Espinosa A, Llanos P, Orellana P, Videla L . Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: Relation to LCPUFA depletion in liver and extrahepatic tissues. Prostaglandins Leukot Essent Fatty Acids. 2015; 98:7-14. DOI: 10.1016/j.plefa.2015.04.002. View

14.

Giroud M, Pisani D, Karbiener M, Barquissau V, Ghandour R, Tews D . miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function. Mol Metab. 2016; 5(8):615-625. PMC: 5021678. DOI: 10.1016/j.molmet.2016.06.005. View

15.

Janus A, Szahidewicz-Krupska E, Mazur G, Doroszko A . Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders. Mediators Inflamm. 2016; 2016:3634948. PMC: 4931075. DOI: 10.1155/2016/3634948. View

16.

Pettersson A, Mejhert N, Jernas M, Carlsson L, Dahlman I, Laurencikiene J . Twist1 in human white adipose tissue and obesity. J Clin Endocrinol Metab. 2010; 96(1):133-41. DOI: 10.1210/jc.2010-0929. View

17.

Floch N, Kolodziejski J, Akkari L, Simonin Y, Ansieau S, Puisieux A . Modulation of oxidative stress by twist oncoproteins. PLoS One. 2013; 8(8):e72490. PMC: 3742535. DOI: 10.1371/journal.pone.0072490. View

18.

Lu S, Guan Q, Liu Y, Wang H, Xu W, Li X . Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity. Lipids Health Dis. 2012; 11:17. PMC: 3285521. DOI: 10.1186/1476-511X-11-17. View

19.

Chang A, Liu Y, Ayyanathan K, Benner C, Jiang Y, Prokop J . An evolutionarily conserved DNA architecture determines target specificity of the TWIST family bHLH transcription factors. Genes Dev. 2015; 29(6):603-16. PMC: 4378193. DOI: 10.1101/gad.242842.114. View

20.

Chattopadhyay M, Khemka V, Chatterjee G, Ganguly A, Mukhopadhyay S, Chakrabarti S . Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects. Mol Cell Biochem. 2014; 399(1-2):95-103. DOI: 10.1007/s11010-014-2236-7. View