1. Academic Validation
  2. L-carnitine alleviates synovitis in knee osteoarthritis by regulating lipid accumulation and mitochondrial function through the AMPK-ACC-CPT1 signaling pathway

L-carnitine alleviates synovitis in knee osteoarthritis by regulating lipid accumulation and mitochondrial function through the AMPK-ACC-CPT1 signaling pathway

  • J Orthop Surg Res. 2023 May 26;18(1):386. doi: 10.1186/s13018-023-03872-9.
Taiyang Liao # 1 2 3 Wei Mei # 1 2 Li Zhang 1 2 3 Liang Ding 1 2 Nan Yang 1 2 3 Peimin Wang 4 5 Li Zhang 6 7
Affiliations

Affiliations

  • 1 Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
  • 2 Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China.
  • 3 Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 4 Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. wangpeimin@njucm.edu.cn.
  • 5 Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China. wangpeimin@njucm.edu.cn.
  • 6 Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. fsyy00725@njucm.edu.cn.
  • 7 Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China. fsyy00725@njucm.edu.cn.
  • # Contributed equally.
Abstract

Background: Knee osteoarthritis (KOA) is a disability-associated condition that is rapidly growing with the increase in obesity rates worldwide. There is a pressing need for precise management and timely intervention in the development of KOA. L-carnitine has been frequently recommended as a supplement to increase physical activity in obese individuals due to its role in fatty acid metabolism, immune disorders, and in maintaining the mitochondrial acetyl-CoA/CoA ratio. In this study, we aimed to investigate the anti-inflammatory effects of L-carnitine on KOA and delineate a potential molecular mechanism.

Methods: Lipopolysaccharide-stimulated primary rat fibroblast-like synoviocytes (FLS) were treated with an AMP-activated protein kinase (AMPK) inhibitor or siRNA and carnitine palmitoyltransferase 1 (CPT1) siRNA to examine the synovial protective effects of L-carnitine. An anterior cruciate ligament transection model of rats was treated with an AMPK agonist (metformin) and CPT1 inhibitor (etomoxir) to define the therapeutic effects of L-carnitine.

Results: L-carnitine displayed a protective effect against synovitis of KOA in vitro and in vivo experiments. Specifically, L-carnitine treatment can reduce synovitis by inhibiting AMPK-ACC-CPT1 pathway activation and showed an increase in fatty acid β-oxidation, a lower lipid accumulation, and a noticeable improvement in mitochondrial function.

Conclusions: Our data suggested that L-carnitine can mitigate synovitis in FLS and synovial tissue, and the underlying mechanism may be related to improving mitochondrial function and reducing lipid accumulation via the AMPK-ACC-CPT1 signaling pathway. Therefore, L-carnitine may be a potential treatment strategy for KOA.

Keywords

AMPK-ACC-CPT1 pathway; Knee osteoarthritis (KOA); L-carnitine; Lipid accumulation; Mitochondrial function; Synovitis.

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