title: Ellagic acid modulates lipid accumulation in primary human adipocytes and human hepatoma Huh7 cells via discrete mechanisms.
abstract: Previously, we have reported that consumption of a muscadine grape phytochemical powder (MGP) decreased lipid accumulation in high-fat fed mice. The aim of this study was to identify the responsible polyphenolic constituents and elucidate the underlying mechanisms. In mice, MGP supplementation significantly reduced visceral fat mass as well as adipocyte size. To determine whether MGP affects adipogenesis or hypertrophic lipid accumulation, we used a human adipogenic stem cell (hASCs) model. Among the MGP, ellagic acid (EA) was identified as a potent negative regulator of adipogenesis of hASCs. In addition, EA substantially decreased the conversion of [(3)H]-acetyl CoA into fatty acids (FAs), suggesting that EA inhibits de novo synthesis of FA in mature adipocytes. Similarly, MGP supplementation significantly decreased hepatic triglyceride (TG) levels. The TG-lowering effects of EA were confirmed in human hepatoma Huh7 cells. EA reduced [(3)H]-oleic acid esterification into [(3)H]-TG as well as the de novo synthesis of FA from [(3)H]-acetyl CoA in Huh7 cells. Intriguingly, EA also increased oxygen consumption rate and β-oxidation-related gene expression. Taken together, EA attenuated new fat cell formation and FA biosynthesis in adipose tissue, while it reduced the synthesis of TG and FA and increased FA oxidation in the liver. These results suggest that EA exerts unique lipid-lowering effects both in adipose tissue and liver via discrete mechanisms.
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Meshail
authors.initials: M
authors.lastname: Okla
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Inhae
authors.initials: I
authors.lastname: Kang
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: Da Mi
authors.initials: DM
authors.lastname: Kim
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: Vishnupriya
authors.initials: V
authors.lastname: Gourineni
authors.affiliation: Department of Food Science and Technology, Oregon State University, Corvallis, OR, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Shay
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: Liwei
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Food Science and Human Nutrition, University of Florida, Gainesville, FL, USA; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, USA. Electronic address: schung4@unl.edu.
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D045744:Cell Line, Tumor; D004610:Ellagic Acid / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D044949:Kaempferols / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064209:Phytochemicals / Q000494:pharmacology; D011208:Powders / Q000737:chemistry; D011794:Quercetin / Q000494:pharmacology; D027843:Vitis / Q000737:chemistry
chemical_list: D005419:Flavonoids; D044949:Kaempferols; D064209:Phytochemicals; D011208:Powders; D004610:Ellagic Acid; C006552:kaempferol; C040015:myricetin; D011794:Quercetin
keywords: Adipogenesis; Ellagic acid; Liver lipid; Muscadine grape; Obesity