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Research Paper|Volume 11, Issue 24|pp 11922—11936

Suppression of protein degradation by leucine requires its conversion to β-hydroxy-β-methyl butyrate in C2C12 myotubes

Yehui Duan1, Yinzhao Zhong1, Bo Song1, Changbing Zheng2, Kang Xu1, Xiangfeng Kong1, Fengna Li1,3
  • 1Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, Hunan, P. R. China
  • 2Guangdong Provincial Key Laboratory of Animal Nutrition Regulation, South China Agricultural University, Guangzhou, Guangdong, China
  • 3Hunan Co-Innovation Center of Animal Production Safety, CICAPS, Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, Hunan, China
* Equal contribution
Received: August 17, 2019Accepted: November 18, 2019Published: December 24, 2019
https://doi.org/10.18632/aging.102509

Copyright © 2019 Duan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The aims of this study were to investigate whether the inhibitory effect of Leucine (Leu) on starvation-induced protein degradation was mediated by its metabolite β-hydroxy-β-methyl butyrate (HMB), and to explore the mechanisms involved. The results showed that the beneficial effects of Leu on protein degradation and the oxygen consumption rate (OCR) of cells were observed at low levels (0.5 mM) rather than at high levels (10 mM). However, these effects were inferior to those of HMB. Moreover, HMB was able to increase/decrease the proportion of MyHC I/MyHC IIb protein expression, respectively. In these KICD-transfected cells, Leu was approximately as effective as HMB in inhibiting protein degradation and increasing the OCR as well as MyHC I protein expression of cells, and these effects of Leu were reverted to a normal state by mesotrione, a specific suppressor of KICD. In conclusion, HMB seems to be an active metabolite of Leu to suppress muscle protein degradation in a starvation model, and the mechanisms may be associated with improved mitochondrial oxidative capacity in muscle cells.