PMID- 34724561
OWN - NLM
STAT- MEDLINE
DCOM- 20211227
LR  - 20211227
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 478
IP  - 22
DP  - 2021 Nov 26
TI  - Fetuin-A regulates adipose tissue macrophage content and activation in insulin 
      resistant mice through MCP-1 and iNOS: involvement of IFNgamma-JAK2-STAT1 pathway.
PG  - 4027-4043
LID - 10.1042/BCJ20210442 [doi]
AB  - In the context of obesity-induced adipose tissue (AT) inflammation, migration of 
      macrophages and their polarization from predominantly anti-inflammatory to 
      proinflammatory subtype is considered a pivotal event in the loss of adipose 
      insulin sensitivity. Two major chemoattractants, monocyte chemoattractant 
      protein-1 (MCP-1) and Fetuin-A (FetA), have been reported to stimulate macrophage 
      migration into inflamed AT instigating inflammation. Moreover, FetA could notably 
      modulate macrophage polarization, yet the mechanism(s) is unknown. The present 
      study was undertaken to elucidate the mechanistic pathway involved in the actions 
      of FetA and MCP-1 in obese AT. We found that FetA knockdown in high fat diet 
      (HFD) fed mice could significantly subdue the augmented MCP-1 expression and 
      reduce adipose tissue macrophage (ATM) content thereby indicating that MCP-1 is 
      being regulated by FetA. Additionally, knockdown of FetA in HFD mice impeded the 
      expression of inducible nitric oxide synthase (iNOS) reverting macrophage 
      activation from mostly proinflammatory to anti-inflammatory state. It was 
      observed that the stimulating effect of FetA on MCP-1 and iNOS was mediated 
      through interferon gamma (IFNgamma) induced activation of JAK2-STAT1-NOX4 pathway. 
      Furthermore, we detected that the enhanced IFNgamma expression was accounted by the 
      stimulatory effect of FetA upon the activities of both cJun and JNK. Taken 
      together, our findings revealed that obesity-induced FetA acts as a master 
      upstream regulator of AT inflammation by regulating MCP-1 and iNOS expression 
      through JNK-cJun-IFNgamma-JAK2-STAT1 signaling pathway. This study opened a new 
      horizon in understanding the regulation of ATM content and activation in 
      conditions of obesity-induced insulin resistance.
CI  - (c) 2021 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Chattopadhyay, Dipanjan
AU  - Chattopadhyay D
AD  - Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana 
      (Institute of Science), Visva-Bharati (A Central University), Santiniketan 
      731235, West Bengal, India.
FAU - Das, Snehasis
AU  - Das S
AD  - Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana 
      (Institute of Science), Visva-Bharati (A Central University), Santiniketan 
      731235, West Bengal, India.
FAU - Guria, Suktara
AU  - Guria S
AD  - Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana 
      (Institute of Science), Visva-Bharati (A Central University), Santiniketan 
      731235, West Bengal, India.
FAU - Basu, Soumyadeep
AU  - Basu S
AD  - Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana 
      (Institute of Science), Visva-Bharati (A Central University), Santiniketan 
      731235, West Bengal, India.
FAU - Mukherjee, Sutapa
AU  - Mukherjee S
AUID- ORCID: 0000-0002-5304-4598
AD  - Endocrinology and Metabolism Laboratory, Department of Zoology, Siksha Bhavana 
      (Institute of Science), Visva-Bharati (A Central University), Santiniketan 
      731235, West Bengal, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Ahsg protein, mouse)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (alpha-2-HS-Glycoprotein)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Adipose Tissue/*immunology/pathology
MH  - Animals
MH  - Chemokine CCL2/*immunology
MH  - *Macrophages/cytology/immunology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase Type II/*immunology
MH  - Obesity/*immunology
MH  - RAW 264.7 Cells
MH  - Stromal Cells
MH  - alpha-2-HS-Glycoprotein/*immunology
OTO - NOTNLM
OT  - Fetuin-A
OT  - IFNgamma;
OT  - MCP-1
OT  - adipose tissue macrophage
OT  - inflammation
OT  - insulin resistance
EDAT- 2021/11/02 06:00
MHDA- 2021/12/28 06:00
CRDT- 2021/11/01 17:23
PHST- 2021/06/18 00:00 [received]
PHST- 2021/10/29 00:00 [revised]
PHST- 2021/11/01 00:00 [accepted]
PHST- 2021/11/02 06:00 [pubmed]
PHST- 2021/12/28 06:00 [medline]
PHST- 2021/11/01 17:23 [entrez]
AID - 230144 [pii]
AID - 10.1042/BCJ20210442 [doi]
PST - ppublish
SO  - Biochem J. 2021 Nov 26;478(22):4027-4043. doi: 10.1042/BCJ20210442.