title: Conjugated Linoleic Acid Isomers Exert Differential Effects on an Adipocyte Model of HIV-associated Lipodystrophy.
abstract: HIV-associated lipodystrophy is associated with decreased expression of PPAR-γ in adipose tissue. Conjugated linoleic acid (CLA) isomers (cis9, trans11 and trans10, cis12) are putative PPAR-γ agonists, but have not previously been investigated in the context of HIVassociated lipodystrophy.
  
  
  
  3T3-L1 pre-adipocytes were differentiated in the presence of ritonavir (20 μM as per previous experimental models) and 100 μM cis9,trans11, trans10,cis12 or vehicle control, DMSO. Microarray analysis, RT-PCR, DNA binding ELISA and Oil Red O staining were used to investigate adipocyte gene expression and binding, protein secretion and triglyceride storage.
  
  
  
  trans10, cis12 + ritonavir altered the expression of 2160 gene transcripts greater than 1.5-fold compared with control, while 257 gene transcripts were altered by cis9,trans11 + ritonavir (P<0.001). trans10,cis12 + ritonavir down-regulated Pparg (-1.55) and Adipoq (-2.95), as well as differentiation (Fcor (-4.78-fold), Arl4a (-4.84), Itga6 (-2.45), Id4 (-2.01)) and triglyceride storage genes (Mrap (- 8.25), Scd1 (-4.34), Lipin1 (-2.52)). Changes in Adipoq were confirmed by RT-PCR (P=0.038) and adiponectin secretion by ELISA (P= 0.003). cis9,trans11 + ritonavir increased PPAR-γ nuclear binding to its gene response element (P=0.038). Both isomers increased triglyceride storage in the presence of ritonavir (P<0.001).
  
  
  
  In the presence of ritonavir, trans10, cis12 appears to be detrimental, while cis9, trans11 was beneficial and may mediate its effects via PPAR-γ. Further research is required to determine the potential role of CLA isomers as therapeutic agents in the management of HIV-associated lipodystrophy.
authors.affiliation: King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, London, SE1 9NH, United Kingdom.
authors.forename: Cathríona R
authors.initials: CR
authors.lastname: Loonam
authors.forename: Sandra D
authors.initials: SD
authors.lastname: O'Dell
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sharp
authors.forename: Anne
authors.initials: A
authors.lastname: Mullen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D039682:HIV-Associated Lipodystrophy Syndrome / Q000503:physiopathology*; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D051379:Mice; D046228:Microarray Analysis; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013194:Staining and Labeling
chemical_list: D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma
keywords: Antiretroviral therapy; HIV-associated lipodystrophy; PPAR-γ; conjugated linoleic acid; ritonavir