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.