Tohoku J. Exp. Med., 2022 February, 256(2)

TRPV1 Protect against Hyperglycemia and Hyperlipidemia Induced Liver Injury via OPA1 in Diabetes

Ting Wang,¹ Yingmei Chen,¹ Yong Li,² Zhen Wang,¹ Chenming Qiu,¹ Dachun Yang¹ and Ken Chen^3,4

¹Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, China
²Department of Cardiology, The People’s Hospital of Chaotian District in Guangyuan, Guangyuan, Sichuan, China
³Department of Cardiology, Chongqing Renji Hospital, University of Chinese Academy of Sciences, Chongqing, China
⁴Department of Cardiology, The Fifth People’s Hospital of Chongqing, Chongqing, China

Type 2 diabetes mellitus (T2DM)-associated mitochondrial impairment may a key factor leading to liver injury. Transient receptor potential receptor vanilloid 1 (TRPV1) regulates the energy expenditure and cholesterol metabolism in hepatocytes and protects against oxidative toxicity. Optic atrophy 1 (OPA1) is involved in the protection of TRPV1 on cardiac microvascular and lung injury. The aim of this study is to identify the role of TRPV1 in redox signals and liver protection via OPA1. TRPV1 knockout (TRPV1^-/-) mice were used. And T2DM associated liver injury was induced by high glucose and high fatty acid (HG/HF) treatment. Mechanisms were studied by TUNEL staining, transmission electron microscope (TEM) analysis, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting in vivo and in vitro. We determined that HG/HF treatment increased TRPV1 expression in liver tissues and AML12 cells. The knockout of TRPV1 increased the apoptotic hepatocytes rate. The inhibition of TRPV1 by 5'-iRTX in HG/HF group elevated the reactive oxygen species (ROS) levels, whereas TRPV1 agonist capsaicin reduced ROS. Our studies also showed that the OPA1 expression was lower in livers from HG/HF treated mice than the control, and genetic ablation of TRPV1 decreased OPA1 expression to a greater extent than the HG/HF mice. The protective effects of TRPV1 on mitochondrial were blocked by OPA1 siRNA. In conclusion, our study showed that the identified regulation of TRPV1 to OPA1 has important implication to the pathogenesis of T2DM-associated liver injury. Targeting the action of TRPV1 and OPA1 presents a potential therapeutic intervention.

Keywords —— mitochondria; OPA1; TRPV1; type 2 diabetes mellitus

© 2022 Tohoku University Medical Press

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Tohoku J. Exp. Med 2022, 256, 131-139.

Correspondence:Ken Chen, M.D., Ph.D., Department of Cardiology, Chongqing Renji Hospital, University of Chinese Academy of Sciences and The Fifth People’s Hospital of Chongqing, No. 24 Renji Road, Nan’an District, Chongqing 400062, P.R. China.

e-mail: ck_tmmu@sina.com

Dachun Yang, M.D., Ph.D., Department of Cardiology, The General Hospital of Western Theater Command, No. 270 Rongdu Ave., Jinniu District, Chengdu, Sichuan 610083, P.R. China.

e-mail: yangdc71@126.com