trans-10,cis-12-Conjugated linoleic acid instigates inflammation in human adipocytes compared with preadipocytes.
We showed previously in cultures of primary human adipocytes and preadipocytes that lipopolysaccharide and trans-10,cis-12-conjugated linoleic acid (10,12-CLA) activate the inflammatory signaling that promotes insulin resistance. Because our published data demonstrated that preadipocytes are the primary instigators of inflammatory signaling in lipopolysaccharide-treated cultures, we hypothesized that they played the same role in 10,12-CLA-mediated inflammation. To test this hypothesis, we employed four distinct models. In model 1, a differentiation model, CLA activation of MAPK and induction of interleukin-8 (IL-8), IL-6, IL-1beta, and cyclo-oxygenase-2 (COX-2) were greatest in differentiated compared with undifferentiated cultures. In model 2, a cell separation model, the mRNA levels of these inflammatory proteins were increased by 10,12-CLA compared with bovine serum albumin vehicle in the adipocyte fraction and the preadipocyte fraction. In model 3, a co-culture insert model, inserts containing approximately 50% adipocytes (AD50) or approximately 100% preadipocytes (AD0) were suspended over wells containing AD50 or AD0 cultures. 10,12-CLA-induced IL-8, IL-6, IL-1beta, and COX-2 mRNA levels were highest in AD50 cultures when co-cultured with AD0 inserts. In model 4, a conditioned medium (CM) model, CM collected from CLA-treated AD50 but not AD0 cultures induced IL-8 and IL-6 mRNA levels and activated phosphorylation of MAPK in naive AD0 and AD50 cultures. Consistent with these data, 10,12-CLA-mediated secretions of IL-8 and IL-6 from AD50 cultures were higher than from AD0 cultures. Notably, blocking adipocytokine secretion prevented the inflammatory capacity of CM from 10,12-CLA-treated cultures. These data suggest that CLA instigates the release of inflammatory signals from adipocytes that subsequently activate adjacent preadipocytes.
Martinez
Kristina
K
Department of Nutrition, University of North Carolina, Greensboro, North Carolina 27402-6170, USA.
Kennedy
Arion
A
West
Tiffany
T
Milatovic
Dejan
D
Aschner
Michael
M
McIntosh
Michael
M
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D005260:Female; D006801:Humans; D007249:Inflammation; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism
D017077:Culture Media, Conditioned; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C496197:trans-10,cis-12-conjugated linoleic acid