title: Trans-10,cis-12 conjugated linoleic acid (CLA) interferes with lipid droplet accumulation during 3T3-L1 preadipocyte differentiation.
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.
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Yeganeh
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada; Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Carla G
authors.initials: CG
authors.lastname: Taylor
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Leslee
authors.initials: L
authors.lastname: Tworek
authors.affiliation: Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada.
authors.forename: Jenna
authors.initials: J
authors.lastname: Poole
authors.affiliation: Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada; Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Canada. Electronic address: peterz@sbrc.ca.
authors.forename: Peter
authors.initials: P
authors.lastname: Zahradka
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D066292:Lipid Droplets / Q000378:metabolism*; D051379:Mice; D000070778:Perilipin-1 / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002227:Carbazoles; D044243:Linoleic Acids, Conjugated; D000070778:Perilipin-1; C000602979:Plin1 protein, mouse; D014280:Triglycerides; C081021:Go 6976; C496630:Prkca protein, mouse; D051571:Protein Kinase C-alpha
keywords: Adipocytes; Conjugated linoleic acid (CLA); Hormone-sensitive lipase; Lipolysis; PKCα; Perilipin-1