AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Food Science and Human Wellness Article
PDF (3.7 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Microbial phenolic metabolites 3-(3’,4’-dihydroxyphenyl)propanoic acid and 3’,4’-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet

Wanbing Chena,b,c,d,1, Ruonan Liua,b,c,d,1, Xiaoling Zhue, Qun Lua,b,c,d, Hong Yanga,b, Rui Liua,b,c,d( )
College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430000, China
Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of education, Wuhan 430000, China
Wuhan Engineering Research Center of Bee Products on Quality and Safety Control, Wuhan 430000, China
Key Laboratory of Urban Agriculture in Central China, Ministry of Agriculture and Rural Affairs, Wuhan 430000, China
Hubei Provincial Institute for Food Supervision and Test, Wuhan 430070, China

1 Wanbing Chen and Ruonan Liu contributed equally to this work and are both fi rst author.

Peer review under responsibility of Tsinghua University Press.

Show Author Information

Abstract

Obesity is associated with numerous metabolic disorders, and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity. However, the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid (DHPA) and 3’,4’-dihydroxyphenylacetic acid (DHAA), two main metabolites of dietary polyphenols, on obesity remains poorly understood. In this study, DHPA and DHAA were found to alleviate obesity, as well as regulate insulin resistance, lipid metabolism, and oxidative stress response in high-fat diet (HFD)mice. Surprisingly, the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome, but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion, tyrosine metabolism, pentose phosphate and tricarboxylic acid (TCA) cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Correlation analysis revealed that the differential metabolites are strongly associated with body weight, blood glucose, insulin level, and superoxide dismutase (SOD) enzyme activity. Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose, lipid and tyrosine metabolism pathways.

Keywords

ObesityDietary polyphenol metabolitesGut microbiotaMetabonomics

References

[1]

J.Y. Xia, D.M. Lloyd-Jones, S.S. Khan, Association of body mass index with mortality in cardiovascular disease: new insights into the obesity paradox from multiple perspectives, Trends Cardiovasc. Med. 29 (2019) 220-225. https://doi.org/10.1016/j.tcm.2018.08.006.
Crossref Google Scholar
[2]

L.W. Amp, W.J. Circulation, Correction to: heart disease and stroke statistics—2018 update: a report from the american heart association, Circulation 137 (2018) e493. https://doi.org/10.1161/CIR.0000000000000558.
Crossref Google Scholar
[3]

M. Rosenbaum, R. Knight, R.L. Leibel, et al., The gut microbiota in human energy homeostasis and obesity, Trends Endocrinol. Metab. Sep. 26 (2015) 493-501. https://doi.org/10.1016/j.tem.2015.07.002.
Crossref Google Scholar
[4]

S. Moossavi, F. Bishehsari, Microbes: possible link between modern lifestyle transition and the rise of metabolic syndrome, Obes. Rev. 20 (2019) 407-419. https://doi.org/10.1111/obr.12784.
Crossref Google Scholar
[5]

A.M. de Oliveira, A.F.S. de Freitas, M.D.S. Costa, et al., Pilosocereus gounellei (Cactaceae) stem extract decreases insulin resistance, inflammation, oxidative stress, and cardio-metabolic risk in diet-induced obese mice, J. Ethnopharmacol. 265 (2021) 113327. https://doi.org/10.1016/j.jep.2020.113327.
Crossref Google Scholar
[6]

M. Werdermann, I. Berger, L.D. Scriba, et al., Insulin and obesity transforms hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state, Mol. Metab. 43 (2020) 101112. https://doi.org/10.1016/j.molmet.2020.101112.
Crossref Google Scholar
[7]

N.M. Hasan, K.F. Johnson, J. Yin, et al., Intestinal stem cell derived enteroids from morbidly obese patients preserve obesity-related phenotypes: elevated glucose absorption and gluconeogenesis, Mol. Metab. 44 (2021) 101129. https://doi.org/10.1016/j.molmet.2020.101129.
Crossref Google Scholar
[8]

M.H. Abu Bakar, M.R. Sarmidi, K.K. Cheng, et al., Metabolomics-the complementary field in systems biology: a review on obesity and type 2 diabetes, Mol. Biosyst. 11 (2015) 1742-1774. https://doi.org/doi:10.1039/c5mb00158g.
Crossref Google Scholar
[9]

L. Men, Z. Pi, Y. Zhou, et al., Urine metabolomics of high-fat diet induced obesity using UHPLC-Q-TOF-MS, J. Pharm. Biomed. Anal. 132 (2017) 258-266. https://doi.org/10.1016/j.jpba.2016.10.012.
Crossref Google Scholar
[10]

M. Chen, B. Lu, Y. Li, et al., Metabolomics insights into the modulatory effects of long-term compound polysaccharide intake in high-fat dietinduced obese rats, Nutr. Metab. (Lond) 15 (2018) 8. https://doi.org/10.1186/s12986-018-0246-2.
Crossref Google Scholar
[11]

L. Wang, B. Zeng, Z. Liu, et al., Green tea polyphenols modulate colonic microbiota diversity and lipid metabolism in high-fat diet treated HFA mice, J. Food Sci. 83 (2018) 864-873. https://doi.org/10.1111/1750-3841.14058.
Crossref Google Scholar
[12]

M. Mahmoudi, K. Charradi, F. Limam, et al., Grape seed and skin extract as an adjunct to xenical therapy reduces obesity, brain lipotoxicity and oxidative stress in high fat diet fed rats, Obes. Res. Clin. Pract. 12 (2018) 115-126. https://doi.org/10.1016/j.orcp.2016.04.006.
Crossref Google Scholar
[13]

C.D. Kay, G. Pereira-Caro, I.A. Ludwig, et al., Anthocyanins and flavanones are more bioavailable than previously perceived: a review of recent evidence, Annu. Rev. Food Sci. Technol. 8 (2017) 155-180. https://doi.org/10.1146/annurev-food-030216-025636.
Crossref Google Scholar
[14]

R.Y. Gan, H.B. Li, Z.Q. Sui, et al., Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): an updated review, Crit. Rev. Food Sci. Nutr. 58 (2018) 924-941. https://doi.org/10.1080/10408398.2016.1231168.
Crossref Google Scholar
[15]

W. Chen, X. Zhu, Q. Lu, et al., C-ring cleavage metabolites of catechin and epicatechin enhanced antioxidant activities through intestinal microbiota, Food Res. Int. 135 (2020) 109271. https://doi.org/10.1016/j.foodres.2020.109271.
Crossref Google Scholar
[16]

G. Borges, J.I. Ottaviani, J.J.J. van der Hooft, et al., Absorption, metabolism, distribution and excretion of (−)-epicatechin: a review of recent findings, Mol. Aspects. Med. 61 (2017) 18-30. https://doi.org/10.1016/j.mam.2017.11.002.
Crossref Google Scholar
[17]

G.V. Slot, H.U. Humpf, Degradation and metabolism of catechin, epigallocatechin-3-gallate (EGCG), and related compounds by the intestinal microbiota in the pig cecum model, J. Agric. Food Chem. 57 (2009) 8041-8048. https://doi.org/10.1021/jf900458e.
Crossref Google Scholar
[18]

G. Pereira-Caro, S. Gaillet, J.L. Ordóñez, et al., Bioavailability of red wine and grape seed proanthocyanidins in rats, Food Funct. 11 (2020) 3986-4001. https://doi.org/10.1039/d0fo00350f.
Crossref Google Scholar
[19]

V. Agullo, D. Villano, C. Garcia-Viguera, et al., Anthocyanin metabolites in human urine after the intake of new functional beverages, Molecules 25(2020) 371. https://doi.org/10.3390/molecules25020371.
Crossref Google Scholar
[20]

L. Duan, C. Zhang, Y. Zhao, et al., Comparison of bioactive phenolic compounds and antioxidant activities of different parts of Taraxacum mongolicum, Molecules 25 (2020) 3260. https://doi.org/10.3390/molecules25143260.
Crossref Google Scholar
[21]

I. Gil-Sánchez, C. Cueva, M. Sanz-Buenhombre, et al., Dynamic gastrointestinal digestion of grape pomace extracts: bioaccessible phenolic metabolites and impact on human gut microbiota, J. Food Compos. Anal. 68(2018) 41-52. https://doi.org/10.1016/j.jfca.2017.05.005.
Crossref Google Scholar
[22]

J. Taile, A. Arcambal, P. Clerc, et al., Medicinal plant polyphenols attenuate oxidative stress and improve inflammatory and vasoactive markers in cerebral endothelial cells during hyperglycemic condition, Antioxidants (Basel) 9 (2020) 573. https://doi.org/10.3390/antiox9070573.
Crossref Google Scholar
[23]

L.M. Harms, A. Scalbert, R. Zamora-Ros, et al., Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations: a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, Br. J. Nutr. 123 (2020) 198-208. https://doi.org/10.1017/S0007114519002538.
Crossref Google Scholar
[24]

W. Chen, L. Zhang, L. Zhao, et al., Metabolomic profiles of A-type procyanidin dimer and trimer with gut microbiota in vitro, J. Funct. Foods 85 (2021) 104637. https://doi.org/10.1016/j.jff.2021.104637.
Crossref Google Scholar
[25]

J. Yang, I. Martínez, J. Walter, et al., In vitro characterization of the impact of selected dietary fibers on fecal microbiota composition and short chain fatty acid production, Anaerobe 23 (2013) 74-81. https://doi.org/10.1016/j.anaerobe.2013.06.012.
Crossref Google Scholar
[26]

J. Zhang, Y. Zhao, D. Ren, et al., Effect of okra fruit powder supplementation on metabolic syndrome and gut microbiota diversity in high fat diet-induced obese mice, Food Res. Int. 130 (2020) 108929. https://doi.org/10.1016/j.foodres.2019.108929.
Crossref Google Scholar
[27]

S.H. Duncan, G.E. Lobley, G. Holtrop, et al., Human colonic microbiota associated with diet, obesity and weight loss, Int. J. Obes. (Lond) 32 (2008) 1720-1724. https://doi.org/10.1038/ijo.2008.155.
Crossref Google Scholar
[28]

R.E. Ley, P.J. Turnbaugh, S. Klein, et al., Human gut microbes associated with obesity, Nature 444 (2006) 1022-1023. https://doi.org/10.1038/4441022a.
Crossref Google Scholar
[29]

F. Castello, G. Costabile, L. Bresciani, et al., Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans, Arch. Biochem. Biophys. 646 (2018) 1-9. https://doi.org/10.1016/j.abb.2018.03.021.
Crossref Google Scholar
[30]

A. Serra, A. Macia, M.P. Romero, et al., Metabolic pathways of the colonic metabolism of flavonoids (flavonols, flavones and flavanones) and phenolic acids, Food Chem. 130 (2012) 383-393. https://doi.org/10.1016/j.foodchem.2011.07.055.
Crossref Google Scholar
[31]

A. Rodriguez-Mateos, D. Vauzour, C.G Krueger, et al., Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update, Arch. Toxicol. 88 (2014) 1803-1853. https://doi.org/10.1007/s00204-014-1330-7.
Crossref Google Scholar
[32]

M. de Ligt, M. Bergman, R.M. Fuentes, et al., No effect of resveratrol supplementation after 6 months on insulin sensitivity in overweight adults: a randomized trial, Am. J. Clin. Nutr. 112 (2020) 1029-1038. https://doi.org/10.1093/ajcn/nqaa125.
Crossref Google Scholar
[33]

R. Khlifi, Z. Dhaouefi, I.B. Toumia, et al., Erica multiflora extract rich in quercetin-3-O-glucoside and kaempferol-3-O-glucoside alleviates high fat and fructose diet-induced fatty liver disease by modulating metabolic and inflammatory pathways in Wistar rats, J. Nutr. Biochem. 86 (2020) 108490. https://doi.org/10.1016/j.jnutbio.2020.108490.
Crossref Google Scholar
[34]

S. Francque, G. Szabo, M.F. Abdelmalek, et al., Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors, Nat. Rev. Gastroenterol. Hepatol. 18 (2020) 24-39. https://doi.org/10.1038/s41575-020-00366-5.
Crossref Google Scholar
[35]

S.M. Sparks, C. Aquino, P. Banker, et al., Exploration of phenylpropanoic acids as agonists of the free fatty acid receptor 4 (FFA4): identification of an orally efficacious FFA4 agonist, Bioorg. Med. Chem. Lett. 27 (2017) 1278-1283. https://doi.org/10.1016/j.bmcl.2017.01.034.
Crossref Google Scholar
[36]

Y. Yang, T. Li, W. Li, et al., Effect of 4-hydroxyphenylacetic acid on M1 macrophage polarization and the formation of macrophage-derived foam cells, Food and Machinery 12 (2020) 2-6. https://doi.org/10.13652/j.issn.1003-5788.2020.12.001.
Crossref Google Scholar
[37]

L. Zhao, F. Zhang, X. Ding, et al., Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes, Science 359 (2018) 1151-1156. https://doi.org/10.1126/science.aao5774.
Crossref Google Scholar
[38]

Z. Cheng, F. Almeida, Mitochondrial alteration in type 2 diabetes and obesity: an epigenetic link, Cell Cycle 13 (2014) 890-897. https://doi.org/10.4161/cc.28189.
Crossref Google Scholar
[39]

K. Sharma, Obesity and diabetic kidney disease: role of oxidant stress and redox balance, Antioxid. Redox. Signal 25 (2016) 208-216. https://doi.org/10.1089/ars.2016.6696.
Crossref Google Scholar
[40]

N. Alkhouri, L.J. Dixon, A.E. Feldstein, Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal, Expert. Rev. Gastroenterol. Hepatol. 3 (2009) 445-451. https://doi.org/10.1586/egh.09.32.
Crossref Google Scholar
[41]

D. Álvarez-Cilleros, M. Á. Martín, L. Goya, et al., (−)-Epicatechin and the colonic metabolite 3,4-dihydroxyphenylacetic acid protect renal proximal tubular cell against high glucose-induced oxidative stress by modulating NOX-4/SIRT-1 signalling, J. Funct. Foods 46 (2018) 19-28. https://doi.org/10.1016/j.jff.2018.04.051.
Crossref Google Scholar
[42]

P. Wang, J. Gao, W. Ke, et al., Resveratrol reduces obesity in high-fat diet-fed mice via modulating the composition and metabolic function of the gut microbiota, Free Radic. Biol. Med. 156 (2020) 83-98. https://doi.org/10.1016/j.freeradbiomed.2020.04.013.
Crossref Google Scholar
[43]

C. Yang, Z. Xu, Q. Deng, et al., Beneficial effects of flaxseed polysaccharides on metabolic syndrome via gut microbiota in high-fat diet fed mice, Food Res. Int. 131 (2020) 108994. https://doi.org/10.1016/j.foodres.2020.108994.
Crossref Google Scholar
[44]

Y. Konishi, S. Kobayashi, Transepithelial transport of chlorogenic acid, caffeic acid, and their colonic metabolites in intestinal Caco-2 cell monolayers, J. Agric. Food Chem. 52 (2004) 2518-2526. https://doi.org/10.1021/jf035407c.
Crossref Google Scholar
[45]

S. Sadeghi Ekbatan, M. Iskandar, L. Sleno, et al., Absorption and metabolism of phenolics from digests of polyphenol-rich potato extracts using the Caco-2/HepG2 co-culture system, Foods 7 (2018). https://doi.org/10.3390/foods7010008.
Crossref Google Scholar
[46]

G. Pereira-Caro, M.N. Clifford, T. Polyviou, et al., Plasma pharmacokinetics of (poly)phenol metabolites and catabolites after ingestion of orange juice by endurance trained men, Free Radic. Biol. Med. 160 (2020) 784-795. https://doi.org/10.1016/j.freeradbiomed.2020.09.007.
Crossref Google Scholar
[47]

Q. Nie, H. Chen, J. Hu, et al., Arabinoxylan attenuates type 2 diabetes by improvement of carbohydrate, lipid, and amino acid metabolism, Mol. Nutr. Food Res. 62 (2018) e1800222. https://doi.org/10.1002/mnfr.201800222.
Crossref Google Scholar
[48]

L. Li, Y. Wang, J. Yuan, et al., Undaria pinnatifida improves obesity-related outcomes in association with gut microbiota and metabolomics modulation in high-fat diet-fed mice, Appl. Microbiol. Biotechnol. 104 (2020) 10217-10231. https://doi.org/10.1007/s00253-020-10954-9.
Crossref Google Scholar
[49]

Y. Liu, Y. Luo, X. Wang, et al., Gut microbiome and metabolome response of Pu-erh tea on metabolism disorder induced by chronic alcohol consumption, J. Agric. Food Chem. 68 (2020) 6615-6627. https://doi.org/10.1021/acs.jafc.0c01947.
Crossref Google Scholar
[50]

M. Monagas, M. Urpi-Sarda, F. Sanchez-Patan, et al., Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites, Food Funct. 1 (2010) 233-253. https://doi.org/10.1039/c0fo00132e.
Crossref Google Scholar
[51]

S. Masumoto, S. Aoki, T. Miura, et al., Flavan-3-ol/procyanidin metabolomics in rat urine using HPLC-quadrupole TOF/MS, Mol. Nutr. Food Res. 62 (2018) e1700867. https://doi.org/10.1002/mnfr.201700867.
Crossref Google Scholar
[52]

S.J. Moon, W. Dong, G.N. Stephanopoulos, et al., Oxidative pentose phosphate pathway and glucose anaplerosis support maintenance of mitochondrial NADPH pool under mitochondrial oxidative stress, Bioeng. Transl. Med. 5 (2020) e10184. https://doi.org/10.1002/btm2.10184.
Crossref Google Scholar
[53]

K.C. Patra, N. Hay, The pentose phosphate pathway and cancer, Trends Biochem. Sci. 39 (2014) 347-354. https://doi.org/10.1016/j.tibs.2014.06.005.
Crossref Google Scholar
[54]

Z. Zhu, T. Umehara, N. Tsujita, et al., Itaconate regulates the glycolysis/pentose phosphate pathway transition to maintain boar sperm linear motility by regulating redox homeostasis, Free Radic. Biol. Med. 159 (2020) 44-53. https://doi.org/10.1016/j.freeradbiomed.2020.07.008.
Crossref Google Scholar
[55]

P. Koivunen, M. Hirsila, A.M. Remes, et al., Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF, J. Biol. Chem. 282 (2007) 4524-4532. https://doi.org/10.1074/jbc.M610415200.
Crossref Google Scholar
[56]

D. Dodd, M.H. Spitzer, W. van Treuren, et al., A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites, Nature 551 (2017) 648-652. https://doi.org/10.1038/nature24661.
Crossref Google Scholar
[57]

A. Agus, J. Planchais, H. Sokol, Gut microbiota regulation of tryptophan metabolism in health and disease, Cell Host. Microbe. 23 (2018) 716-724. https://doi.org/10.1016/j.chom.2018.05.003.
Crossref Google Scholar
[58]

M. Arnoriaga-Rodriguez, J. Mayneris-Perxachs, A. Burokas, et al., Obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids, Cell Metab. 32 (2020) 548-560 e547. https://doi.org/10.1016/j.cmet.2020.09.002.
Crossref Google Scholar
[59]

Y. Yao, H. Chen, L. Yan, et al., Berberine alleviates type 2 diabetic symptoms by altering gut microbiota and reducing aromatic amino acids, Biomed. Pharmacother. 131 (2020) 110669. https://doi.org/10.1016/j.biopha.2020.110669.
Crossref Google Scholar
[60]

A.P. Okekunle, X. Wu, R. Feng, et al., Higher intakes of energy-adjusted dietary amino acids are inversely associated with obesity risk, Amino Acids 51 (2019) 373-382. https://doi.org/10.1007/s00726-018-2672-x.
Crossref Google Scholar
[61]

S. Bel-Serrat, T. Mouratidou, I. Huybrechts, et al., The role of dietary fat on the association between dietary amino acids and serum lipid profile in European adolescents participating in the HELENA study, Eur. J. Clin. Nutr. 68 (2014) 464-473. https://doi.org/10.1038/ejcn.2013.284.
Crossref Google Scholar
[62]

H.M. Roager, T.R. Licht, Microbial tryptophan catabolites in health and disease, Nat. Commun. 9 (2018) 3294. https://doi.org/10.1038/s41467-018-05470-4.
Crossref Google Scholar
[63]

X. Li, Z.H. Zhang, H.M. Zabed, et al., An insight into the roles of dietary tryptophan and its metabolites in intestinal inflammation and inflammatory bowel disease, Mol. Nutr. Food Res. 65 (2021) e2000461. https://doi.org/10.1002/mnfr.202000461.
Crossref Google Scholar
[64]

W. Di, J. Lv, S. Jiang, et al., PGC-1: the energetic regulator in cardiac metabolism, Curr. Issues. Mol. Biol. 28 (2018) 29-46. https://doi.org/10.21775/cimb.028.029.
Crossref Google Scholar
[65]

B. Gross, M. Pawlak, P. Lefebvre, et al., PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD, Nat. Rev. Endocrinol. 13 (2017) 36-49. https://doi.org/10.1038/nrendo.2016.135.
Crossref Google Scholar
[66]

T. Wood Dos Santos, Q. Cristina Pereira, L. Teixeira, et al., Effects of polyphenols on thermogenesis and mitochondrial biogenesis, Int. J. Mol. Sci. 19 (2018) 2757. https://doi.org/10.3390/ijms19092757.
Crossref Google Scholar
Food Science and Human Wellness
Volume 13 Issue 1,
January 2024
Pages 327-338
DOI: 10.26599/FSHW.2022.9250027
Cite this article:
Chen W, Liu R, Zhu X, et al. Microbial phenolic metabolites 3-(3’,4’-dihydroxyphenyl)propanoic acid and 3’,4’-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet. Food Science and Human Wellness, 2024, 13(1): 327-338. https://doi.org/10.26599/FSHW.2022.9250027

2125

Views

396

Downloads

7

Crossref

6

Web of Science

8

Scopus

0

CSCD

Altmetrics
Received: 28 March 2022
Revised: 05 May 2022
Accepted: 22 June 2022
Published: 01 June 2023
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return