title: Eicosapentaenoic acid and arachidonic acid differentially regulate adipogenesis, acquisition of a brite phenotype and mitochondrial function in primary human adipocytes.
abstract: n-3 and n-6 PUFAs have several opposing biological effects and influence white adipose tissue (WAT) function. The recent discovery of thermogenic UCP1-expressing brite adipocytes within WAT raised the question whether n-3 and n-6 PUFAs exert differential effects on brite adipocyte formation and mitochondrial function.
  
  
  
  Primary human preadipocytes were treated with n-3 PUFAs (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or n-6 PUFA (arachidonic acid, ARA) during differentiation, and adipogenesis, white and brite gene expression markers, mitochondrial content and function were analyzed at day 12 of differentiation. Adipogenesis was equally increased by n-3 and n-6 PUFAs. The n-6 PUFA ARA increased lipid droplet size and expression of the white-specific marker TCF21 while decreased mitochondrial protein expression and respiratory function. In contrast, EPA increased expression of the brown adipocyte-related genes UCP1 and CPT1B, and improved mitochondrial function of adipocytes. The opposing effects of EPA and ARA on gene expression and mitochondrial function were also observed in cells treated from day 8 to 12 of adipocyte differentiation.
  
  
  
  EPA promotes brite adipogenesis and improves parameters of mitochondrial function, such as increased expression of CPTB1, citrate synthase activity and higher maximal respiratory capacity, while ARA reduced mitochondrial spare respiratory capacity in vitro.
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.|German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Fleckenstein-Elsen
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.|German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dinnies
authors.affiliation: German Center for Diabetes Research, Partner Düsseldorf, Germany.|Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelenik
authors.affiliation: German Center for Diabetes Research, Partner Düsseldorf, Germany.|Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.|German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Romacho
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany. Eckel@uni-duesseldorf.de.|German Center for Diabetes Research, Partner Düsseldorf, Germany. Eckel@uni-duesseldorf.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Eckel
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics
chemical_list: C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; C542591:CPT1B protein, human; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase
keywords: Adipogenesis; Brite adipocyte; Human adipocytes; Mitochondrial function; Polyunsaturated fatty acids