Reduced expression of collagen VI alpha 3 (COL6A3) confers resistance to inflammation-induced MCP1 expression in adipocytes.
Collagen VI alpha 3 (COL6A3) is associated with insulin resistance and adipose tissue inflammation. In this study, the role of COL6A3 in human adipocyte function was characterized.



Immortalized human preadipocyte cell lines stably expressing control or COL6A3 shRNA were used to study adipocyte function and inflammation.



COL6A3 knockdown increased triglyceride content, lipolysis, insulin-induced Akt phosphorylation, and mRNA expression of key adipogenic genes (peroxisome proliferator-activated receptor-γ, glucose transporter, adiponectin, and fatty acid binding protein), indicating increased adipocyte function and insulin sensitivity. However, COL6A3 knockdown decreased basal adipocyte chemokine (C-C motif) ligand 2 [CCL2, monocyte chemoattractant protein (MCP1)] mRNA expression, reduced secreted protein levels, and abrogated tumor necrosis factor-α- and lipopolysaccharide-induced MCP1 mRNA expression. In addition, while control adipocytes co-cultured with THP1 macrophages showed a threefold increase in adipocyte MCP1 mRNA expression, in COL6A3 knockdown adipocytes MCP1 mRNA expression was unaltered by co-culturing. Lastly, in normal differentiated adipocytes, matrix metalloproteinase-11 treatment reduced expression of COL6A3 protein, MCP1 mRNA, MCP1 secretion, and abrogated tumor necrosis factor-α- and lipopolysaccharide-induced MCP1 mRNA expression and protein secretion.



COL6A3 knockdown in adipocytes leads to the development of a unique state of inflammatory resistance via suppression of MCP1 induction.
BERG, LLC, Framingham, Massachusetts, USA.
Stephane
S
Gesta
BERG, LLC, Framingham, Massachusetts, USA.
Kalyani
K
Guntur
BERG, LLC, Framingham, Massachusetts, USA.
Ishita Deb
ID
Majumdar
BERG, LLC, Framingham, Massachusetts, USA.
Syamala
S
Akella
BERG, LLC, Framingham, Massachusetts, USA.
Vivek K
VK
Vishnudas
BERG, LLC, Framingham, Massachusetts, USA.
Rangaprasad
R
Sarangarajan
BERG, LLC, Framingham, Massachusetts, USA.
Niven R
NR
Narain
D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D024142:Collagen Type VI / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*
C499918:ADIPOQ protein, human; D052242:Adiponectin; D018932:Chemokine CCL2; D024142:Collagen Type VI; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; D003094:Collagen