PMID- 32197417 OWN - NLM STAT- MEDLINE DCOM- 20201201 LR - 20201201 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 6 DP - 2020 Mar 18 TI - Ellagic Acid and Urolithins A and B Differentially Regulate Fat Accumulation and Inflammation in 3T3-L1 Adipocytes While Not Affecting Adipogenesis and Insulin Sensitivity. LID - 10.3390/ijms21062086 [doi] LID - 2086 AB - Ellagic acid (EA) is a component of ellagitannins, present in crops such as pecans, walnuts, and many berries, which metabolized by the gut microbiota forms urolithins A, B, C, or D. In this study, ellagic acid, as well as urolithins A and B, were tested on 3T3-L1 preadipocytes for differentiation and lipid accumulation. In addition, inflammation was studied in mature adipocytes challenged with lipopolysaccharide (LPS). Results indicated that EA and urolithins A and B did not affect differentiation (adipogenesis) and only EA and urolithin A attenuated lipid accumulation (lipogenesis), which seemed to be through gene regulation of glucose transporter type 4 (GLUT4) and adiponectin. On the other hand, gene expression of cytokines and proteins associated with the inflammation process indicate that urolithins and EA differentially inhibit tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Urolithins A and B were found to reduce nuclear levels of phosphorylated nuclear factor kappaB (p-NF-kappaB), whereas all treatments showed expression of nuclear phosphorylated protein kinase B (p-AKT) in challenged LPS cells when treated with insulin, indicating the fact that adipocytes remained insulin sensitive. In general, urolithin A is a compound able to reduce lipid accumulation, without affecting the protein expression of peroxisome proliferator-activated receptor-gamma (PPARgamma), CCAAT/enhancer binding protein-alpha (c/EBPalpha), and PPARalpha, whereas EA and urolithin B were found to enhance PPARgamma and c/EBPalpha protein expressions as well as fatty acid (FA) oxidation, and differentially affected lipid accumulation. FAU - Cisneros-Zevallos, Luis AU - Cisneros-Zevallos L AD - Department of Horticultural Sciences, Texas A&M University, College Station, TX 77843-2133, USA. AD - Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA. FAU - Bang, Woo Young AU - Bang WY AD - Department of Horticultural Sciences, Texas A&M University, College Station, TX 77843-2133, USA. FAU - Delgadillo-Puga, Claudia AU - Delgadillo-Puga C AD - Departamento de Nutricion Animal Dr. Fernando Perez-Gil Romo, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ), CDMX 14080, Mexico. LA - eng PT - Journal Article DEP - 20200318 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Coumarins) RN - 0 (urolithin B) RN - 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one) RN - 19YRN3ZS9P (Ellagic Acid) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*metabolism MH - Adipogenesis/*drug effects MH - Animals MH - Coumarins/*pharmacology MH - Ellagic Acid/*pharmacology MH - *Insulin Resistance MH - Lipogenesis/*drug effects MH - Mice PMC - PMC7139477 OTO - NOTNLM OT - 3T3-L1 adipocytes OT - adipogenesis OT - ellagic acid OT - inflammation OT - insulin sensitivity OT - lipid metabolism OT - urolithins A and B COIS- The authors declare no conflict of interest. EDAT- 2020/03/22 06:00 MHDA- 2020/12/02 06:00 PMCR- 2020/03/01 CRDT- 2020/03/22 06:00 PHST- 2019/12/14 00:00 [received] PHST- 2020/03/10 00:00 [revised] PHST- 2020/03/11 00:00 [accepted] PHST- 2020/03/22 06:00 [entrez] PHST- 2020/03/22 06:00 [pubmed] PHST- 2020/12/02 06:00 [medline] PHST- 2020/03/01 00:00 [pmc-release] AID - ijms21062086 [pii] AID - ijms-21-02086 [pii] AID - 10.3390/ijms21062086 [doi] PST - epublish SO - Int J Mol Sci. 2020 Mar 18;21(6):2086. doi: 10.3390/ijms21062086.