Urolithin A, C and D, but not iso-Urolithin A and Urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes

Authors

Inhae Kang, University of Nebraska-LincolnFollow
YongEun Kim, University of Nebraska-Lincoln
Francisco A. Tomás-Barberán, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
Juan Carlos Espín, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
Soonkyu Chung, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2016

Citation

Molecular Nutrition & Food Research p. 1-29 2016

Comments

This article is protected by copyright. All rights reserved.

Abstract

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, B, C, D, and iso-UroA, were used to determine the effect of Uro on adipogenesis and lipogenesis. Individual Uro (30 M) were added to human adipogenic stem cells (hASCs) during differentiation. UroA, C and D, 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, C, and D attenuated TG accumulation, while increasing the FA oxidation in adipocytes and hepatoma Huh7 cells. Furthermore, UroC, D and A promoted the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that Uro may alter energy-sensing metabolic pathways in primary human adipocytes.

Conclusions: Taken together, our results demonstrated that UroA, C, and D, but not isoUroA and UroB, reduce TG accumulation and increase FA oxidation in adipocytes as well as hepatocytes.