Obesity by High-Fat Diet Increases Pain Sensitivity by Reprogramming Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia

Nan Lian; Kaiteng Luo; Huijing Xie; Yi Kang; Kuo Tang; Peilin Lu; Tao Li

doi:10.3389/fnut.2022.902635

Obesity by High-Fat Diet Increases Pain Sensitivity by Reprogramming Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia

Front Nutr. 2022 May 12:9:902635. doi: 10.3389/fnut.2022.902635. eCollection 2022.

Authors

Nan Lian^{1

2

3}, Kaiteng Luo^{1

2}, Huijing Xie^{1

2}, Yi Kang^{1

2}, Kuo Tang^{1

2}, Peilin Lu^{1

2}, Tao Li^{1

2}

Affiliations

¹ Department of Anesthesiology, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China.
² Laboratory of Mitochondria and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
³ Department of Radiology, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China.

Abstract

Obesity is a significant health concern as a result of poor-quality diet, for example, high-fat diet (HFD). Although multiple biological and molecular changes have been identified to contribute to HFD-induced pain susceptibility, the mechanisms are not fully understood. Here, we show that mice under 8 weeks of HFD were sensitive to mechanical and thermal stimuli, which was coupled with an accumulation of branched-chain amino acids (BCAAs) in lumbar dorsal root ganglia (DRG) due to local BCAA catabolism deficiency. This HFD-induced hyperalgesic phenotype could be exacerbated by supply of excessive BCAAs or mitigated by promotion of BCAA catabolism via BT2 treatment. In addition, our results suggested that HFD-related pain hypersensitivity was associated with a pro-inflammatory status in DRG, which could be regulated by BCAA abundance. Therefore, our study demonstrates that defective BCAA catabolism in DRG facilitates HFD-induced pain hypersensitivity by triggering inflammation. These findings not only reveal metabolic underpinnings for the pathogenesis of HFD-related hyperalgesia but also offer potential targets for developing diet-based therapy of chronic pain.

Keywords: branched-chain amino acids; high-fat diet; inflammation; obesity; pain behaviors.