Individual Saturated and Monounsaturated Fatty Acids Trigger Distinct Transcriptional Networks in Differentiated 3T3-L1 Preadipocytes

<b><i>Background/Aims:</i></b> Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). <b><i>Methods:</i></b> Differentiated preadipocytes were treated with either 250 µ<smlcap>M</smlcap> PA, SA, PMA, or OA for 48 h. Gene expression was analyzed using microarrays and real-time RT-PCR. Data were compared with those of a previous study reporting AT gene expression in humans following the consumption of SFA- or MUFA-enriched diets. <b><i>Results:</i></b> Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling and a reduction in TLR signalling. <i>Ccl5</i> was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. <b><i>Conclusions:</i></b> Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids.