PMID- 26872561 OWN - NLM STAT- MEDLINE DCOM- 20171205 LR - 20180117 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 60 IP - 5 DP - 2016 May TI - Urolithin A, C, and D, but not iso-urolithin A and urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes. PG - 1129-38 LID - 10.1002/mnfr.201500796 [doi] AB - SCOPE: 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. METHODS AND RESULTS: UroA, UroB, UroC, UroD, and iso-UroA were used to determine the effect of Uro on adipogenesis and lipogenesis. Individual Uro (30 muM) 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. CONCLUSIONS: 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. CI - (c) 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Kang, Inhae AU - Kang I AD - Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA. FAU - Kim, YongEun AU - Kim Y AD - Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA. FAU - Tomas-Barberan, Francisco A AU - Tomas-Barberan FA AD - Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain. FAU - Espin, Juan Carlos AU - Espin JC AD - Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain. FAU - Chung, Soonkyu AU - Chung S AD - Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20160413 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Coumarins) RN - 0 (Hydrolyzable Tannins) RN - 0 (Triglycerides) RN - 0 (urolithin B) RN - 0 (urolithin C) RN - 0 (urolithin D) RN - 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one) SB - IM MH - Adipocytes/*drug effects/metabolism MH - Adipogenesis/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Coumarins/*pharmacology MH - Hepatocytes/*drug effects/metabolism MH - Humans MH - Hydrolyzable Tannins/*pharmacology MH - Lipid Metabolism/drug effects MH - Triglycerides/metabolism OTO - NOTNLM OT - AMP-activated protein kinase OT - Adipogenesis OT - Ellagic acid OT - Lipogenesis OT - Urolithins EDAT- 2016/02/14 06:00 MHDA- 2017/12/06 06:00 CRDT- 2016/02/14 06:00 PHST- 2015/10/09 00:00 [received] PHST- 2016/01/30 00:00 [revised] PHST- 2016/02/03 00:00 [accepted] PHST- 2016/02/14 06:00 [entrez] PHST- 2016/02/14 06:00 [pubmed] PHST- 2017/12/06 06:00 [medline] AID - 10.1002/mnfr.201500796 [doi] PST - ppublish SO - Mol Nutr Food Res. 2016 May;60(5):1129-38. doi: 10.1002/mnfr.201500796. Epub 2016 Apr 13.