title: Urolithin A, C, and D, but not iso-urolithin A and urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes.
abstract: Urolithins (Uro) are ellagic acid (EA)-derived metabolites produced by gut microbes. There is a growing interest in the biological activities of Uro. Our aim was to evaluate the impacts of Uro on regulating triglyceride (TG) accumulation using cultures of primary human adipocytes and hepatoma Huh7 cells.
  
  
  
  UroA, UroB, UroC, UroD, and iso-UroA were used to determine the effect of Uro on adipogenesis and lipogenesis. Individual Uro (30 μM) were added to human adipogenic stem cells during differentiation. UroA, UroC, and UroD, but not iso-UroA and UroB, significantly inhibited new fat cell formation by decreasing TG accumulation and adipogenic protein and gene expressions. The regulation of TG synthesis by Uro was investigated via metabolic chasing with radiolabeled precursors. UroA, UroC, and UroD attenuated TG accumulation, while increasing the fatty acid (FA) oxidation in adipocytes and h/epatoma Huh7 cells. Furthermore, UroC, UroD, and UroA promoted the phosphorylation of AMP-activated protein kinase, suggesting that Uro may alter energy-sensing metabolic pathways in primary human adipocytes.
  
  
  
  Taken together, our results demonstrated that UroA, UroC, and UroD, but not isoUroA and UroB, reduce TG accumulation and increase FA oxidation in adipocytes as well as hepatocytes.
authors.affiliation: Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Inhae
authors.initials: I
authors.lastname: Kang
authors.affiliation: Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: YongEun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.affiliation: Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espín
authors.affiliation: Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
chemical_list: D003374:Coumarins; D047348:Hydrolyzable Tannins; D014280:Triglycerides; C000595064:urolithin B; C588364:urolithin C; C000595063:urolithin D; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
keywords: AMP-activated protein kinase; Adipogenesis; Ellagic acid; Lipogenesis; Urolithins