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

Molecular Nutrition and Food Research

Volumn 60, Issue 5, 2016, Pages 1129-1138

  Kang, Inhae ^a   Kim, Yongeun ^a   Tomás Barberán, Francisco A ^b   Espín, Juan Carlos ^b   Chung, Soonkyu ^a  

^a UNIVERSITY OF NEBRASKA LINCOLN   (United States)

^b RESEARCH GROUP ON QUALITY   (Spain)

Author keywords

Adipogenesis; AMP activated protein kinase; Ellagic acid; Lipogenesis; Urolithins

Indexed keywords

3,8-DIHYDROXY-6H-DIBENZO(B,D)PYRAN-6-ONE; COUMARIN DERIVATIVE; TANNIN; TRIACYLGLYCEROL; UROLITHIN B; UROLITHIN C; UROLITHIN D;

ADIPOCYTE; ADIPOGENESIS; CELL CULTURE; CELL SURVIVAL; DRUG EFFECTS; HUMAN; LIPID METABOLISM; LIVER CELL; METABOLISM;

ADIPOCYTES; ADIPOGENESIS; CELL SURVIVAL; CELLS, CULTURED; COUMARINS; HEPATOCYTES; HUMANS; HYDROLYZABLE TANNINS; LIPID METABOLISM; TRIGLYCERIDES;

EID: 84963647506     PISSN: 16134125     EISSN: 16134133     Source Type: Journal    
DOI: 10.1002/mnfr.201500796     Document Type: Article

References (48)

1. Yu, Y. M., Chang, W. C., Wu, C. H., Chiang, S. Y., Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid. J. Nutr. Biochem. 2005, 16, 675-681.
2. Park, S. H., Kim, J. L., Lee, E. S., Han, S. Y. et al., Dietary ellagic acid attenuates oxidized LDL uptake and stimulates cholesterol efflux in murine macrophages. J. Nutr. 2011, 141, 1931-1937.
3. Losso, J. N., Bansode, R. R., Trappey, A., Bawadi, H. A. et al., In vitro anti-proliferative activities of ellagic acid. J. Nutr. Biochem. 2004, 15, 672-678.
4. Panchal, S. K., Ward, L., Brown, L., Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. Eur. J. Nutr. 2013, 52, 559-568.
5. Lei, F., Zhang, X. N., Wang, W., Xing, D. M. et al., Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int. J. Obes. 2007, 31, 1023-1029.
6. Gourineni, V., Shay, N. F., Chung, S., Sandhu, A. K. et al., Muscadine grape (Vitis rotundifolia) and wine phytochemicals prevented obesity-associated metabolic complications in C57BL/6J mice. J. Agric. Food Chem. 2012, 60, 7674-7681.
7. Kang, I., Okla, M., Chung, S., Ellagic acid inhibits adipocyte differentiation through coactivator-associated arginine methyltransferase 1-mediated chromatin modification. J. Nutr. Biochem. 2014, 25, 946-953.
8. Okla, M., Kang, I., Kim, D. M., Gourineni, V. et al., Ellagic acid modulates lipid accumulation in primary human adipocytes and human hepatoma Huh7 cells via discrete mechanisms. J. Nutr. Biochem. 2015, 26, 82-90.
9. González-Sarrías, A., García-Villalba, R., Núñez-Sánchez, M. A., Tomé-Carneiro, J. et al., Identifying the limits for ellagic acid bioavailability: a crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts (DOI: 10.1016). J. Funct. Foods 2015, 19, 225-235.
10. Seeram, N. P., Lee, R., Heber, D., Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin. Chim. Acta 2004, 348, 63-68.
11. Garcia-Villalba, R., Beltran, D., Espin, J. C., Selma, M. V. et al., Time course production of urolithins from ellagic acid by human gut microbiota. J. Agric. Food Chem. 2013, 61, 8797-8806.
12. Espin, J. C., Larrosa, M., Garcia-Conesa, M. T., Tomas-Barberan, F., Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far. Evid. Based Complement. Altern. Med. 2013, 2013, 270418.
13. Tomas-Barberan, F. A., Garcia-Villalba, R., Gonzalez-Sarrias, A., Selma, M. V. et al., Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status. J. Agric. Food Chem. 2014, 62, 6535-6538.
14. Cerda, B., Espin, J. C., Parra, S., Martinez, P. et al., The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans. Eur. J. Nutr. 2004, 43, 205-220.
15. Seeram, N. P., Henning, S. M., Zhang, Y., Suchard, M. et al., Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. J. Nutr. 2006, 136, 2481-2485.
16. Nunez-Sanchez, M. A., Garcia-Villalba, R., Monedero-Saiz, T., Garcia-Talavera, N. V. et al., Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol. Nutr. Food Res. 2014, 58, 1199-1211.
17. Larrosa, M., Gonzalez-Sarrias, A., Yanez-Gascon, M. J., Selma, M. V. et al., Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. J. Nutr. Biochem. 2010, 21, 717-725.
18. Gonzalez-Sarrias, A., Gimenez-Bastida, J. A., Nunez-Sanchez, M. A., Larrosa, M. et al., Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells. Eur. J. Nutr. 2014, 53, 853-864.
19. Adams, L. S., Zhang, Y., Seeram, N. P., Heber, D. et al., Pomegranate ellagitannin-derived compounds exhibit antiproliferative and antiaromatase activity in breast cancer cells in vitro. Cancer Prev. Res. 2010, 3, 108-113.
20. Verzelloni, E., Pellacani, C., Tagliazucchi, D., Tagliaferri, S. et al., Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites. Mol. Nutr. Food Res. 2011, 55(Suppl 1), S35-S43.
21. Bialonska, D., Kasimsetty, S. G., Khan, S. I., Ferreira, D., Urolithins, intestinal microbial metabolites of pomegranate ellagitannins, exhibit potent antioxidant activity in a cell-based assay. J. Agric. Food Chem. 2009, 57, 10181-10186.
22. Garcia-Villalba, R., Espin, J. C., Tomas-Barberan, F. A., Chromatographic and spectroscopic characterization of urolithins for their determination in biological samples after the intake of foods containing ellagitannins and ellagic acid. J. Chromatogr. A 2016, 8, 162-175.
23. Bligh, E. G., Dyer, W. J., A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 1959, 37, 911-917.
24. Olpin, S. E., Manning, N. J., Pollitt, R. J., Clarke, S., Improved detection of long-chain fatty acid oxidation defects in intact cells using [9, 10-3H]oleic acid. J. Inherit. Metab. Dis. 1997, 20, 415-419.
25. Hwang, J. T., Park, I. J., Shin, J. I., Lee, Y. K. et al., Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem. Biophys. Res. Commun. 2005, 338, 694-699.
26. Jeong, M. Y., Kim, H. L., Park, J., An, H. J. et al., Rubi fructus (Rubus coreanus) inhibits differentiation to adipocytes in 3T3-L1 cells. Evid. Based Complement. Altern. Med. 2013, 2013, 475386.
27. Chen, S., Li, Z., Li, W., Shan, Z. et al., Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can. J. Physiol. Pharmacol. 2011, 89, 793-799.
28. Choi, H. S., Jeon, H. J., Lee, O. H., Lee, B. Y., Dieckol, a major phlorotannin in Ecklonia cava, suppresses lipid accumulation in the adipocytes of high-fat diet-fed zebrafish and mice: inhibition of early adipogenesis via cell-cycle arrest and AMPKalpha activation. Mol. Nutr. Food Res. 2015, 59, 1458-1471.
29. Hardie, D. G., Ross, F. A., Hawley, S. A., AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 2012, 13, 251-262.
30. Gonzalez-Sarrias, A., Espin, J. C., Tomas-Barberan, F. A., Garcia-Conesa, M. T., Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to ellagic acid and its metabolites, urolithins. Mol. Nutr. Food Res. 2009, 53, 686-698.
31. Piwowarski, J. P., Kiss, A. K., Granica, S., Moeslinger, T., Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages. Mol. Nutr. Food Res. 2015, 59, 2168-2177.
32. Backhed, F., Ding, H., Wang, T., Hooper, L. V. et al., The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 2004, 101, 15718-15723.
33. Backhed, F., Manchester, J. K., Semenkovich, C. F., Gordon, J. I., Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl. Acad. Sci. USA 2007, 104, 979-984.
34. Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V. et al., An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444, 1027-1031.
35. Selma, M. V., Romo-Vaquero, M., García-Villalba, R., Gonzalez-Sarrias, A. et al., The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism. Food Funct. 2016, doi: 10.1039/C5FO01100K. [Epub ahead of print].
36. Selma, M. V., Beltran, D., Garcia-Villalba, R., Espin, J. C. et al., Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species. Food Funct. 2014, 5, 1779-1784.
37. Clavel, T., Desmarchelier, C., Haller, D., Gerard, P. et al., Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance. Gut Microbes 2014, 5, 544-551.
38. Espin, J. C., Gonzalez-Barrio, R., Cerda, B., Lopez-Bote, C. et al., Iberian pig as a model to clarify obscure points in the bioavailability and metabolism of ellagitannins in humans. J. Agric. Food Chem. 2007, 55, 10476-10485.
39. Cho, H., Jung, H., Lee, H., Yi, H. C. et al., Chemopreventive activity of ellagitannins and their derivatives from black raspberry seeds on HT-29 colon cancer cells. Food Funct. 2015, 6, 1675-1683.
40. Pedram, A., Razandi, M., Blumberg, B., Levin, E. R., Membrane and nuclear estrogen receptor alpha collaborate to suppress adipogenesis but not triglyceride content. FASEB J. 2016, 30, 230-240.
41. Larrosa, M., Gonzalez-Sarrias, A., Garcia-Conesa, M. T., Tomas-Barberan, F. A. et al., Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J. Agric. Food Chem. 2006, 54, 1611-1620.
42. Kiss, A. K., Granica, S., Stolarczyk, M., Melzig, M. F., Epigenetic modulation of mechanisms involved in inflammation: influence of selected polyphenolic substances on histone acetylation state. Food Chem. 2012, 131, 1015-1020.
43. Mandal, S., Shivapurkar, N. M., Galati, A. J., Stoner, G. D., Inhibition of N-nitrosobenzylmethylamine metabolism and DNA binding in cultured rat esophagus by ellagic acid. Carcinogenesis 1988, 9, 1313-1316.
44. Teel, R. W., Ellagic acid binding to DNA as a possible mechanism for its antimutagenic and anticarcinogenic action. Cancer Lett. 1986, 30, 329-336.
45. Canto, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M. et al., AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009, 458, 1056-1060.
46. Kahn, B. B., Alquier, T., Carling, D., Hardie, D. G., AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005, 1, 15-25.
47. Wang, L., Li, L., Ran, X., Long, M. et al., Ellagic acid reduces adipogenesis through inhibition of differentiation-prevention of the induction of Rb phosphorylation in 3T3-L1 adipocytes. Evid. Based Complement. Altern. Med. 2013, 2013, 287534.
48. Cao, K., Xu, J., Pu, W., Dong, Z. et al., Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation. Sci. Rep. 2015, 5, 14014.