Trans-10,cis-12 conjugated linoleic acid (CLA) interferes with lipid droplet accumulation during 3T3-L1 preadipocyte differentiation |
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| Affiliation: | 1. Minerva Foundation Institute for Medical Research, Biomedicum 2U, FI-00290 Helsinki, Finland;2. Department of Medicine, University of Helsinki, FI-00014 Finland;3. University of Helsinki and Helsinki University Hospital, Obstetrics and Gynecology, FI-00029 HUS, Helsinki, Finland;4. Folkhälsan Research Center, FI-00290 Helsinki, Finland;5. National Institute for Health and Welfare/Public Health Genomics Unit, Biomedicum, FI-00290 Helsinki, Finland;6. Department of Surgery, Helsinki University Central Hospital, FI-000290 HUS, Helsinki, Finland;7. Institute for Molecular Medicine Finland FIMM, University of Helsinki, FI-00014 Helsinki, Finland;8. Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, D-89075 Ulm, Germany;9. Department of Anatomy, Faculty of Medicine, University of Helsinki, FI-00014 Helsinki, Finland;1. Sichuan Agricultural University, Ya''an 625014, Sichuan, China;2. Virginia Polytechnic Institute and State University, Department of Animal and Poultry Sciences, Blacksburg, Virginia 24061, United States |
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| Abstract: | In this study, we hypothesize that the biologically active isomers of conjugated linoleic acid (CLA), cis-9,trans-11 (c9,t11) and trans-10,cis-12 (t10,c12) CLA, have different effects on early and late stages 3T3-L1 preadipocyte differentiation. Both c9-t11 and t10-c12CLA stimulated early stage pre-adipocyte differentiation (day 2), while t10-c12CLA inhibited late differentiation (day 8) as determined by lipid droplet numbers and both perilipin-1 levels and phosphorylation state. At day 8, the adipokines adiponectin, chemerin and adipsin were all reduced in t10-c12CLA treated cells versus control cells. Immunofluorescence microscopy showed perilipin-1 was present solely on lipid droplets on day 8 in t10-c12 treated 3T3-L1 cells, whereas preilipin-1 was also located in the perinuclear region in control and c9-t11 treated cells. The t10-c12CLA isomer also decreased levels of hormone-sensitive lipase and inhibited lipolysis. These findings indicate that the decrease in lipid droplets caused by t10-c12CLA is the result of an inhibition of lipid droplet production during adipogenesis rather than a stimulation of lipolysis. Additionally, treatment with Gö6976 blocked the effect of t10-c12CLA on perilipin-1 phosphorylation, implicating PKCα in perilipin-1 phosphorylation, and thus a regulator of triglyceride catabolism. These data are supported by evidence that t10-c12CLA activated PKCα. These are the first data to show that CLA isomers can affect lipid droplet dynamics in adipocytes through PKCα. |
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| Keywords: | Conjugated linoleic acid (CLA) Adipocytes Perilipin-1 Hormone-sensitive lipase PKCα Lipolysis |
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