PMID- 31484323
OWN - NLM
STAT- MEDLINE
DCOM- 20200218
LR  - 20200218
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 11
IP  - 9
DP  - 2019 Sep 3
TI  - Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via 
      Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress.
LID - 10.3390/nu11092062 [doi]
LID - 2062
AB  - Recent evidences have linked indole-3-acetic acid (IAA), a gut microbiota-derived 
      metabolite from dietary tryptophan, with the resistance to liver diseases. 
      However, data supporting IAA-mediated protection against nonalcoholic fatty liver 
      disease (NAFLD) from an in vivo study is lacking. In this study, we assessed the 
      role of IAA in attenuating high-fat diet (HFD)-induced NAFLD in male C57BL/6 
      mice. Administration of IAA (50 mg/kg body weight) by intraperitoneal injection 
      was found to alleviate HFD-induced elevation in fasting blood glucose and 
      homeostasis model assessment of insulin resistance (HOMA-IR) index as well as 
      plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), and 
      glutamic-pyruvic transaminase (GPT) activity. Histological examination further 
      presented the protective effect of IAA on liver damage induced by HFD feeding. 
      HFD-induced an increase in liver total triglycerides and cholesterol, together 
      with the upregulation of genes related to lipogenesis including sterol regulatory 
      element binding-protein 1 (Srebf1), steraroyl coenzyme decarboxylase 1 (Scd1), 
      peroxisome proliferator-activated receptor gamma (PPARgamma), acetyl-CoA carboxylase 
      1 (Acaca), and glycerol-3-phosphate acyltransferase, mitochondrial (Gpam), which 
      were mitigated by IAA treatment. The results of reactive oxygen species (ROS) and 
      malonaldehyde (MDA) level along with superoxide dismutase (SOD) activity and 
      glutathione (GSH) content in liver tissue evidenced the protection of IAA against 
      HFD-induced oxidative stress. Additionally, IAA attenuated the inflammatory 
      response of liver in mice exposed to HFD as shown by the reduction in the 
      F4/80-positive macrophage infiltration and the expression of monocyte 
      chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha). In 
      conclusion, our findings uncover that IAA alleviates HFD-induced hepatotoxicity 
      in mice, which proves to be associated with the amelioration in insulin 
      resistance, lipid metabolism, and oxidative and inflammatory stress.
FAU - Ji, Yun
AU  - Ji Y
AUID- ORCID: 0000-0002-3483-0729
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, Beijing 100191, China.
FAU - Gao, Yuan
AU  - Gao Y
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, Beijing 100191, China.
FAU - Chen, Hong
AU  - Chen H
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, Beijing 100191, China.
FAU - Yin, Yue
AU  - Yin Y
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, Beijing 100191, China.
FAU - Zhang, Weizhen
AU  - Zhang W
AUID- ORCID: 0000-0001-8791-2798
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, Beijing 100191, China. weizhenzhang@bjmu.edu.cn.
LA  - eng
GR  - 2017YFC0908900/the National Key R&D Program of China/
GR  - 2018M641113/the Projects funded by China Postdoctoral Science Foundation/
GR  - 81730020/the National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190903
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Indoleacetic Acids)
RN  - 0 (Lipids)
RN  - 6U1S09C61L (indoleacetic acid)
SB  - IM
MH  - Animals
MH  - Indoleacetic Acids/*pharmacology
MH  - Inflammation/*drug therapy
MH  - Lipids/blood
MH  - Lipogenesis/*drug effects
MH  - Liver/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy
MH  - Oxidative Stress/*drug effects
PMC - PMC6769627
OTO - NOTNLM
OT  - NAFLD
OT  - indole-3-acetic acid
OT  - inflammation
OT  - lipid metabolism
OT  - oxidative stress
OT  - steatosis
COIS- The authors declare no conflicts of interest.
EDAT- 2019/09/06 06:00
MHDA- 2020/02/19 06:00
PMCR- 2019/09/01
CRDT- 2019/09/06 06:00
PHST- 2019/08/01 00:00 [received]
PHST- 2019/08/22 00:00 [revised]
PHST- 2019/08/27 00:00 [accepted]
PHST- 2019/09/06 06:00 [entrez]
PHST- 2019/09/06 06:00 [pubmed]
PHST- 2020/02/19 06:00 [medline]
PHST- 2019/09/01 00:00 [pmc-release]
AID - nu11092062 [pii]
AID - nutrients-11-02062 [pii]
AID - 10.3390/nu11092062 [doi]
PST - epublish
SO  - Nutrients. 2019 Sep 3;11(9):2062. doi: 10.3390/nu11092062.