Inflammation triggers high mobility group box 1 (HMGB1) secretion in adipose tissue, a potential link to obesity.
BACKGROUND
Low grade inflammation is one of the major metabolic disorders in case of obesity due to variable secretion of adipose derived cytokines called adipokines. Recently the nuclear protein HMGB1 was identified as an inflammatory alarmin in obesity associated diseases. However HMGB1 role in adipose tissue inflammation is not yet studied.


OBJECTIVE
The aim of this study was to prove the expression of HMGB1 in human adipose tissue and to assess the levels of expression between normo-weight and obese individuals. Furthermore we determined which type of cells within adipose tissue is involved in HMGB1 production under inflammatory signal.


METHODS
Western-blot was performed on protein lysates from human normo-weight and obese adipose tissue to study the differential HMGB1 expression. Human normo-weight adipose tissue, adipose-derived stromal cells (ASCs) and adipocytes were cultured and stimulated with LPS to induce inflammation. HMGB1, IL-6 and MCP-1 secretion and gene expression were quantified by ELISA and Q-PCR respectively, as well as cell death by LDH assay. HMGB1 translocation during inflammation was tracked down by immunofluorescence in ASCs.


RESULTS
HMGB1 was expressed 2-fold more in adipose tissue from obese compared to normo-weight individuals. LPS led to an up-regulation in HMGB1 secretion and gene expression in ASCs, while no change was noticed in adipocytes. Moreover, this HMGB1 release was not attributable to any cell death. In LPS-stimulated ASCs, HMGB1 translocation from nucleus to cytoplasm was detectable at 12h and the nuclear HMGB1 was completely drained out after 24h of treatment.


CONCLUSIONS
The expression level studies between adipose tissue from normo-weight and obese individuals together with in vitro results strongly suggest that adipose tissue secretes HMGB1 in response to inflammatory signals which characterized obesity.
Groupe d'Etude sur l'Inflammation Chronique et l'Obésité (GEICO), University of Reunion Island, CYROI, 2 rue Maxime Rivière, 97 490 Sainte-Clotilde, Reunion.
Manoj Kumar
MK
Gunasekaran
Wildriss
W
Viranaicken
Anne-Claire
AC
Girard
Franck
F
Festy
Maya
M
Cesari
Regis
R
Roche
Laurence
L
Hoareau
D017667:Adipocytes / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
D054392:Adipokines; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D015850:Interleukin-6
HMGB1; Human adipose tissue; Inflammation; Obesity; Primary culture