PMID- 37175792
OWN - NLM
STAT- MEDLINE
DCOM- 20230606
LR  - 20230606
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 9
DP  - 2023 Apr 29
TI  - The Receptor Tyrosine Kinase c-Met Promotes Lipid Accumulation in 3T3-L1 
      Adipocytes.
LID - 10.3390/ijms24098086 [doi]
LID - 8086
AB  - The receptor tyrosine kinase c-Met is elaborated in embryogenesis, morphogenesis, 
      metabolism, cell growth, and differentiation. JNJ38877605 (JNJ) is an inhibitor 
      of c-Met with anti-tumor activity. The c-Met expression and its role in adipocyte 
      differentiation are unknown. Here, we investigated the c-Met expression and 
      phosphorylation, knockdown (KD) effects, and pharmacological inhibition of c-Met 
      by JNJ on fat accumulation in murine preadipocyte 3T3-L1 cells. During 3T3-L1 
      preadipocyte differentiation, strikingly, c-Met expression at the protein and 
      mRNA levels and the protein phosphorylation on Y1234/1235 and Y1349 is crucial 
      for inducing its kinase catalytic activity and activating a docking site for 
      signal transducers were increased in a time-dependent manner. Of note, JNJ 
      treatment at 20 muM that strongly inhibits c-Met phosphorylation without altering 
      its total expression resulted in less lipid accumulation and triglyceride (TG) 
      content with no cytotoxicity. JNJ further reduced the expression of adipogenic 
      regulators, including CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), peroxisome 
      proliferator-activated receptor-gamma (PPAR-gamma), fatty acid synthase (FAS), acetyl CoA 
      carboxylase (ACC), and perilipin A. Moreover, JNJ treatment increased 
      cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) phosphorylation 
      but decreased ATP levels. Significantly, KD of c-Met suppressed fat accumulation 
      and triglyceride (TG) quantity and reduced the expression of C/EBP-alpha, PPAR-gamma, 
      FAS, ACC, and perilipin A. Collectively, the present results demonstrate that 
      c-Met is a novel, highly conserved mediator of adipogenesis regulating lipid 
      accumulation in murine adipocytes.
FAU - Park, Yu-Kyoung
AU  - Park YK
AD  - Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 
      Dalgubeoldaero, Dalseo-gu, Daegu 42601, Republic of Korea.
AD  - Department of Physiology, Senotherapy-Based Metabolic Disease Control Research 
      Center, College of Medicine, Yeungnam University, 170, Hyeonchung-ro, Nam-gu, 
      Daegu 42415, Republic of Korea.
FAU - Jang, Byeong-Churl
AU  - Jang BC
AD  - Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 
      Dalgubeoldaero, Dalseo-gu, Daegu 42601, Republic of Korea.
LA  - eng
GR  - 2022R1A2C1009345/National Research Foundation of Korea/
GR  - 2020-2022/Keimyung University Research Grant/
PT  - Journal Article
DEP - 20230429
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CCAAT-Enhancer-Binding Protein-alpha)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - 0 (Lipids)
RN  - 0 (Perilipins)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (PPAR gamma)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Animals
MH  - Mice
MH  - 3T3-L1 Cells
MH  - Adipocytes/metabolism
MH  - *Adipogenesis/genetics
MH  - CCAAT-Enhancer-Binding Protein-alpha/metabolism
MH  - Cell Differentiation
MH  - Fatty Acid Synthases/metabolism
MH  - Lipid Metabolism
MH  - Lipids/pharmacology
MH  - Perilipins/metabolism
MH  - *Peroxisome Proliferator-Activated Receptors/metabolism
MH  - PPAR gamma/metabolism
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Triglycerides/metabolism
PMC - PMC10179087
OTO - NOTNLM
OT  - 3T3-L1
OT  - AMPK
OT  - JNJ38877605
OT  - c-Met
OT  - lipid accumulation
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/13 15:12
MHDA- 2023/05/15 11:42
PMCR- 2023/04/29
CRDT- 2023/05/13 01:29
PHST- 2023/03/29 00:00 [received]
PHST- 2023/04/23 00:00 [revised]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/05/15 11:42 [medline]
PHST- 2023/05/13 15:12 [pubmed]
PHST- 2023/05/13 01:29 [entrez]
PHST- 2023/04/29 00:00 [pmc-release]
AID - ijms24098086 [pii]
AID - ijms-24-08086 [pii]
AID - 10.3390/ijms24098086 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Apr 29;24(9):8086. doi: 10.3390/ijms24098086.