Title:Conjugated Linoleic Acid Isomers Exert Differential Effects on an Adipocyte Model of HIV-associated Lipodystrophy
VOLUME: 15 ISSUE: 1
Author(s):Cathriona R. Loonam*, Sandra D. O'Dell, Paul A. Sharp and Anne Mullen
Affiliation:King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, London, SE1 9NH, King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, London, SE1 9NH, King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, London, SE1 9NH, King's College London, School of Medicine, Diabetes and Nutritional Sciences Division, London, SE1 9NH
Keywords:Antiretroviral therapy, conjugated linoleic acid, HIV-associated lipodystrophy, PPAR-γ, ritonavir.
Abstract:Background: 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.
Method: 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.
Results: 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).
Conclusion: 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.
