2. Academic Validation
  3. Indole-3-acetic acid improves the hepatic mitochondrial respiration defects by PGC1a up-regulation

Indole-3-acetic acid improves the hepatic mitochondrial respiration defects by PGC1a up-regulation

  • Cell Signal. 2022 Nov;99:110442. doi: 10.1016/j.cellsig.2022.110442.
Chen Zhang 1,  Qingsong Fu 1,  Kai Shao 1,  Limin Liu 1,  Xiaotian Ma 1,  Fengyi Zhang 1,  Xiaodong Zhang 1,  Liying Meng 1,  ChuanZhu Yan 2,  Xiaoyun Zhao 3
Affiliations

Affiliations

  • 1 Department of Medical Experimental Center, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China; Qingdao Key Lab of Mitochondrial Medicine, Hefei Road No 758, Qingdao 266035, China.
  • 2 Qingdao Key Lab of Mitochondrial Medicine, Hefei Road No 758, Qingdao 266035, China; Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, 266035, China; Brain Science Research Institute, Shandong University, Jinan, Shandong, 250012, China.
  • 3 Department of Medical Experimental Center, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China; Qingdao Key Lab of Mitochondrial Medicine, Hefei Road No 758, Qingdao 266035, China. Electronic address: [email protected].
PMID: 35988807 DOI: 10.1016/j.cellsig.2022.110442
Abstract

Recent evidences have linked indole-3-acetic acid (I3A), a gut microbiota-derived metabolite from dietary tryptophan, with the protection against non-alcoholic fatty liver disease (NAFLD). However, the values of I3A on mitochondrial homeostasis in NAFLD have yet to be analyzed. In this study, we verified that I3A alleviated dietary-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis. Importantly, we expanded the understanding of I3A further to enhance mitochondrial oxidative phosphorylation in the liver by RNA-seq. Consistently, I3A restored the deficiency of mitochondrial respiration complex (MRC) capacity in palmitic acid (PA)-induced HepG2 without initiating oxidative stress in vitro. These changes were dependent on Peroxisome Proliferator-activated Receptor γ coactivator 1 (PGC1)-a, a key regulator of mitochondrial biogenesis. Silencing of PGC1a by siRNA and pharmacologic inhibitor SR-18292, blocked the restoration of I3A on mitochondrial oxidative phosphorylation. In addition, pre-treatment of I3A guarded against the deficiency of MRC capacity. In conclusion, our findings uncovered that I3A increased hepatic PGC1a expression, contributing to mitochondrial respiration improvement in NAFLD.

Keywords

Indole-3-acetic acid; Mitochondria; Non-alcoholic fatty liver disease; Oxidative phosphorylation; Peroxisome proliferator-activated receptor gamma coactivator 1-alpha.

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