Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Theranostics 2020; 10(3):1332-1354. doi:10.7150/thno.40021 This issue Cite

Research Paper

Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance

Bili Zhu1*, Ming-Yue Li2*, Quanming Lin1, Zhicheng Liang1, Qihang Xin1, Menghuan Wang1, Zhendan He3, Xiaomei Wang1, Xuli Wu4, George G. Chen2, Peter CY Tong5, Weizhen Zhang6, Li-Zhong Liu1✉

1. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Physiology, Health Science Center, School of Medicine, Shenzhen University, Shenzhen, China
2. Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
3. Key Laboratory of Natural Small Molecular Drugs, School of Pharmacy, Shenzhen University, Shenzhen, China
4. School of Public Health, Shenzhen University, Shenzhen, China
5. Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
6. Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
*These two authors contributed equally to this work.

✉ Corresponding author: Li-Zhong Liu, Department of Physiology, School of Medicine, A7-304, Shenzhen University Xili Campus, Nanshan District, Shenzhen 518055, China. Tel: 86-755-86671936; E-mail: liulzedu.cn

Citation:
Zhu B, Li MY, Lin Q, Liang Z, Xin Q, Wang M, He Z, Wang X, Wu X, Chen GG, Tong PCY, Zhang W, Liu LZ. Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance. Theranostics 2020; 10(3):1332-1354. doi:10.7150/thno.40021. https://www.thno.org/v10p1332.htm
Other styles

File import instruction

Abstract

Graphic abstract

Lipid oversupply may induce CD36 sarcolemmal translocation to facilitate fatty acid transport, which in turn causes dyslipidemia and type 2 diabetes. However, the underlying mechanisms of CD36 redistribution are still yet to be unraveled.

Methods: High fat diet fed mice and palmitate/oleic acid-treated L6 cells were used to investigate the initial events of subcellular CD36 recycling prior to insulin resistance. The regulation of CD36 sarcolemmal translocation by lipid oversupply was assessed by insulin tolerance test (ITT), oral glucose tolerance test (OGTT), glucose/fatty acid uptake assay, surface CD36 and GLUT4 detection, and ELISA assays. To elucidate the underlying mechanisms, specific gene knockout, gene overexpression and/or gene inhibition were employed, followed by Western blot, co-immunoprecipitation, immunostaining, and kinase activity assay.

Results: Upon lipid/fatty acid overload, PKCζ activity and TBC1D1 phosphorylation were enhanced along with increased sarcolemmal CD36. The inhibition of PKCζ or TBC1D1 was shown to block fatty acid-induced CD36 translocation and was synergistic in impairing CD36 redistribution. Mechanically, we revealed that AMPK was located upstream of PKCζ to control its activity whereas Rac1 facilitated PKCζ translocation to the dorsal surface of the cell to cause actin remodeling. Furthermore, AMPK phosphorylated TBC1D1 to release retained cytosolic CD36. The activated PKCζ and phosphorylated TBC1D1 resulted in a positive feedback regulation of CD36 sarcolemmal translocation.

Conclusion: Collectively, our study demonstrated exclusively that lipid oversupply induced CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1, which was as an early event prior to insulin resistance. The acquired data may provide potential therapy targets to prevent lipid oversupply-induced insulin resistance.

Keywords: CD36, fatty acid, PKCζ, TBC1D1

Citation styles

APA
Zhu, B., Li, M.Y., Lin, Q., Liang, Z., Xin, Q., Wang, M., He, Z., Wang, X., Wu, X., Chen, G.G., Tong, P.CY., Zhang, W., Liu, L.Z. (2020). Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance. Theranostics, 10(3), 1332-1354. https://doi.org/10.7150/thno.40021.

ACS
Zhu, B.; Li, M.Y.; Lin, Q.; Liang, Z.; Xin, Q.; Wang, M.; He, Z.; Wang, X.; Wu, X.; Chen, G.G.; Tong, P.CY.; Zhang, W.; Liu, L.Z. Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance. Theranostics 2020, 10 (3), 1332-1354. DOI: 10.7150/thno.40021.

NLM
Zhu B, Li MY, Lin Q, Liang Z, Xin Q, Wang M, He Z, Wang X, Wu X, Chen GG, Tong PCY, Zhang W, Liu LZ. Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance. Theranostics 2020; 10(3):1332-1354. doi:10.7150/thno.40021. https://www.thno.org/v10p1332.htm

CSE
Zhu B, Li MY, Lin Q, Liang Z, Xin Q, Wang M, He Z, Wang X, Wu X, Chen GG, Tong PCY, Zhang W, Liu LZ. 2020. Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance. Theranostics. 10(3):1332-1354.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use