2. Academic Validation
  3. Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice

Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice

  • Hepatology. 2022 Jan;75(1):140-153. doi: 10.1002/hep.32148.
Jingjing Duan 1,  Zhuo Wang 2,  Ran Duan 1,  Chenxinhui Yang 1,  Ruolin Zhao 1,  Qi Feng 1,  Yuanyuan Qin 1,  Jingwei Jiang 1,  Shouyong Gu 3,  Kaiyan Lv 1,  Libo Zhang 1,  Bixia He 1,  Lutz Birnbaumer 4 5,  Song Yang 6,  Zhen Chen 1,  Yong Yang 1
Affiliations

Affiliations

  • 1 Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • 2 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
  • 3 Province Geriatric Hospital, Nanjing, China.
  • 4 Institute of Biomedical Research (BIOMED), Catholic University of Argentina, Buenos Aires, Argentina.
  • 5 Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
  • 6 Center of Hepatology, Beijing Ditan Hospital of Capital Medical University, Beijing, China.
PMID: 34510514 DOI: 10.1002/hep.32148
Abstract

Background and aims: Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity.

Approach and results: In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating Peroxisome Proliferator-activated Receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models.

Conclusions: Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.

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