HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

trans-10,cis-12-Conjugated linoleic acid instigates inflammation in human adipocytes compared with preadipocytes.

Abstract
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.
AuthorsKristina Martinez, Arion Kennedy, Tiffany West, Dejan Milatovic, Michael Aschner, Michael McIntosh
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 23 Pg. 17701-12 (Jun 04 2010) ISSN: 1083-351X [Electronic] United States
PMID20353947 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Culture Media, Conditioned
  • Fatty Acids
  • Linoleic Acids, Conjugated
  • Lipids
  • Lipopolysaccharides
  • RNA, Messenger
  • trans-10,cis-12-conjugated linoleic acid
Topics
  • Adipocytes (cytology, metabolism)
  • Cell Differentiation
  • Coculture Techniques
  • Culture Media, Conditioned (metabolism)
  • Fatty Acids (chemistry)
  • Female
  • Humans
  • Inflammation
  • Linoleic Acids, Conjugated (chemistry, metabolism)
  • Lipids (chemistry)
  • Lipopolysaccharides (chemistry)
  • MAP Kinase Signaling System
  • Phosphorylation
  • RNA, Messenger (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: