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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Obesity | Research article

Obese rats intervened with Rhizoma coptidis revealed differential gene expression and microbiota by serum metabolomics

Authors: Yanhua Ji, Kexin Luo, Jiri Mutu Zhang, Peng Ni, Wangping Xiong, Xiaoquan Luo, Guoliang Xu, Hongning Liu, Zhijun Zeng

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

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Abstract

Background

Integrating systems biology is an approach for investigating metabolic diseases in humans. However, few studies use this approach to investigate the mechanism by which Rhizoma coptidis (RC) reduces the effect of lipids and glucose on high-fat induced obesity in rats.

Methods

Twenty-four specific pathogen-free (SPF) male Sprague–Dawley rats (80 ± 10 g) were used in this study. Serum metabolomics were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry. Liver tissue and cecum feces were used for RNA-Seq technology and 16S rRNA gene sequencing, respectively.

Results

We identified nine potential biomarkers, which are differential metabolites in the Control, Model and RC groups, including linoleic acid, eicosapentaenoic acid, arachidonic acid, stearic acid, and L-Alloisoleucine (p < 0.01). The liver tissue gene expression profile indicated the circadian rhythm pathway was significantly affected by RC (Q ≤ 0.05). A total of 149 and 39 operational taxonomic units (OTUs), which were highly associated with biochemical indicators and potential biomarkers in the cecum samples (FDR ≤ 0.05), respectively, were identified.

Conclusion

This work provides information to better understand the mechanism of the effect of RC intervention on hyperlipidemia and hypoglycemic effects in obese rats. The present study demonstrates that integrating systems biology may be a powerful tool to reveal the complexity of metabolic diseases in rats intervened by traditional Chinese medicine.
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Literature
1.
Rosa-Caldwell ME, Lee DE, Brown JL, Brown LA, Perry RA Jr, Greene ES, Carvallo Chaigneau FR, Washington TA, Greene NP. Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice. Appl Physiol Nutr Metab. 2017;42(2):148–56.PubMedCrossRef
2.
Liu Y, Su D, Zhang L, Wei S, Liu K, Peng M, Li H, Song Y. Endogenous L-carnosine level in diabetes rat cardiac muscle. Evid Based Complement Alternat Med. 2016;2016:6230825.PubMedPubMedCentral
3.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–31.PubMedCrossRef
4.
Waldram A, Holmes E, Wang Y, Rantalainen M, Wilson ID, Tuohy KM, McCartney AL, Gibson GR, Nicholson JK. Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents. J Proteome Res. 2009;8(5):2361–75.PubMedCrossRef
5.
Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, Fu H, Xue X, Lu C, Ma J, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359(6380):1151–6.PubMedCrossRef
6.
De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Backhed F, Mithieux G. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156(1–2):84–96.PubMedCrossRef
7.
den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, Oosterveer MH, Jonker JW, Groen AK, Reijngoud DJ, et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation. Diabetes. 2015;64(7):2398–408.CrossRef
8.
De Vadder F, Kovatcheva-Datchary P, Zitoun C, Duchampt A, Backhed F, Mithieux G. Microbiota-produced succinate improves glucose homeostasis via intestinal gluconeogenesis. Cell Metab. 2016;24(1):151–7.PubMedCrossRef
9.
Mollica MP, Mattace Raso G, Cavaliere G, Trinchese G, De Filippo C, Aceto S, Prisco M, Pirozzi C, Di Guida F, Lama A, et al. Butyrate regulates liver mitochondrial function, efficiency, and dynamics in insulin-resistant obese mice. Diabetes. 2017;66(5):1405–18.PubMedCrossRef
10.
Serena C, Ceperuelo-Mallafre V, Keiran N, Queipo-Ortuno MI, Bernal R, Gomez-Huelgas R, Urpi-Sarda M, Sabater M, Perez-Brocal V, Andres-Lacueva C, et al. Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. ISME J. 2018;12(7):1642–57.PubMedPubMedCentralCrossRef
11.
Wu G, Zhang C, Wang J, Zhang F, Wang R, Shen J, Wang L, Pang X, Zhang X, Zhao L, et al. Diminution of the gut resistome after a gut microbiota-targeted dietary intervention in obese children. Sci Rep. 2016;6:24030.PubMedPubMedCentralCrossRef
12.
Gu Y, Liu C, Zheng N, Jia W, Zhang W, Li H. Metabolic and gut microbial characterization of obesity-prone mice under a high-fat diet. J Proteome Res. 2019;18(4):1703–14.PubMedCrossRef
13.
Barengolts E. Gut microbiota, prebiotics, probiotics, and synbiotics in management of obesity and prediabetes: review of randomized controlled trials. Endocr Pract. 2016;22(10):1224–34.PubMedCrossRef
14.
Li WL, Zheng HC, Bukuru J, De Kimpe N. Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. J Ethnopharmacol. 2004;92(1):1–21.PubMedCrossRef
15.
Yuan L, Tu D, Ye X, Wu J. Hypoglycemic and hypocholesterolemic effects of Coptis chinensis franch inflorescence. Plant Foods Hum Nutr. 2006;61(3):139–44.PubMedCrossRef
16.
Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y. Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J Ethnopharmacol. 2009;126(1):5–17.PubMedCrossRef
17.
Li JY, Wang XB, Luo JG, Kong LY. Seasonal variation of alkaloid contents and anti-inflammatory activity of Rhizoma coptidis based on fingerprints combined with chemometrics methods. J Chromatogr Sci. 2015;53(7):1131–9.PubMedCrossRef
18.
Xie W, Gu D, Li J, Cui K, Zhang Y. Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS One. 2011;6(9):e24520.PubMedPubMedCentralCrossRef
19.
He K, Kou S, Zou Z, Hu Y, Feng M, Han B, Li X, Ye X. Hypolipidemic effects of alkaloids from Rhizoma Coptidis in diet-induced hyperlipidemic hamsters. Planta Med. 2016;82(8):690–7.PubMedCrossRef
20.
Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004;10(12):1344–51.PubMedCrossRef
21.
Wang L, Ye X, Li X, Chen Z, Chen X, Gao Y, Zhao Z, Huang W, Chen X, Yi J. Metabolism, transformation and distribution of Coptis chinensis total alkaloids in rat. Zhongguo Zhong Yao Za Zhi. 2010;35(15):2017–20.PubMed
22.
He K, Hu Y, Ma H, Zou Z, Xiao Y, Yang Y, Feng M, Li X, Ye X. Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways. Biochim Biophys Acta. 2016;1862(9):1696–709.PubMedCrossRef
23.
Zhang X, Zhao Y, Xu J, Xue Z, Zhang M, Pang X, Zhang X, Zhao L. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci Rep. 2015;5:14405.PubMedPubMedCentralCrossRef
24.
Formisano E, Pasta A, Cremonini AL, Favari E, Ronca A, Carbone F, Semino T, Di Pierro F, Sukkar SG, Pisciotta L. Efficacy of nutraceutical combination of monacolin K, berberine, and silymarin on lipid profile and PCSK9 plasma level in a cohort of hypercholesterolemic patients. J Med Food. 2020;23(6):658–66.PubMedCrossRef
25.
26.
Liu KY, Song YG, Liu YL, Peng M, Li HY, Li XL, Feng BW, Xu PF, Su D. An integrated strategy using UPLC-QTOF-MSE and UPLC-QTOF-MRM (enhanced target) for pharmacokinetics study of wine processed Schisandra Chinensis fructus in rats. J Pharmaceut Biomed. 2017;139:165–78.CrossRef
27.
Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C, Li M, Zhang C, Zhang Z, Zhang Y, et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS One. 2012;7(8):e42529.PubMedPubMedCentralCrossRef
28.
Zhang Q, Xu G, Li J, Guo X, Wang H, Li B, Tu J, Zhang H. Metabonomic study on the plasma of streptozotocin-induced diabetic rats treated with Ge Gen Qin Lian Decoction by ultra high performance liquid chromatography-mass spectrometry. J Pharm Biomed Anal. 2016;120:175–80.PubMedCrossRef
29.
Zeng ZJ, Ji YH, Huang X, Jiang YN, Ou ZM, Xiong WP, Li BT, Zhang QY, Nie P, Xu GL, et al. Integrating the Metpa and Ipa to verify the biological function of the potential biomarkers from plasma metabonomics in diabetic rats. Acta Med Mediterr. 2019;35(3):1627–31.
30.
Shi XB, Yang SM, Zhang G, Song YG, Su D, Liu YL, Guo F, Shan LN, Cai JQ. The different metabolism of morusin in various species and its potent inhibition against UDP-glucuronosyltransferase (UGT) and cytochrome p450 (CYP450) enzymes. Xenobiotica. 2016;46(5):467–76.PubMedCrossRef
31.
Shi XB, Zhang G, Ge GB, Guo Z, Song YG, Su D, Shan LN. In vitro metabolism of auriculasin and its inhibitory effects on human cytochrome P450 and UDP-glucuronosyltransferase enzymes. Chem Res Toxicol. 2019;32(10):2125–34.PubMedCrossRef
32.
Zeng ZJ, Gao Y, Liu LY, Yan XJ, Xu GL, Liu HN, Ji YH. Quickly evaluating the synergistic effects of top anti-cancer drugs by the computer high performance computing power and complex network visualization. J Intell Fuzzy Syst. 2020;38(1):277–81.CrossRef
33.
Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022–3.PubMedCrossRef
34.
Munoz-Garach A, Diaz-Perdigones C, Tinahones FJ. Gut microbiota and type 2 diabetes mellitus. Endocrinol Nutr. 2016;63(10):560–8.PubMedCrossRef
35.
He MZ, Fang SM, Huang XC, Zhao YZ, Ke SL, Yang H, Li ZJ, Gao J, Chen CY, Huang LS. Evaluating the contribution of gut microbiota to the variation of porcine fatness with the cecum and fecal samples. Front Microbiol. 2016;7:2108.PubMedPubMedCentralCrossRef
36.
Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JA, Brandsma E, Marczynska J, Imhann F, Weersma RK, et al. The gut microbiome contributes to a substantial proportion of the variation in blood lipids. Circ Res. 2015;117(9):817–24.PubMedPubMedCentralCrossRef
37.
Pang B, Yu XT, Zhou Q, Zhao TY, Wang H, Gu CJ, Tong XL. Effect of Rhizoma coptidis (Huang Lian) on treating diabetes mellitus. Evid Based Complement Alternat Med. 2015;2015:921416.PubMedPubMedCentralCrossRef
38.
Ge AH, Bai Y, Li J, Liu J, He J, Liu EW, Zhang P, Zhang BL, Gao XM, Chang YX. An activity-integrated strategy involving ultra-high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and fraction collector for rapid screening and characterization of the alpha-glucosidase inhibitors in Coptis chinensis Franch. (Huanglian). J Pharm Biomed Anal. 2014;100:79–87.PubMedCrossRef
39.
Chang YX, Ge AH, Donnapee S, Li J, Bai Y, Liu J, He J, Yang X, Song LJ, Zhang BL, et al. The multi-targets integrated fingerprinting for screening anti-diabetic compounds from a Chinese medicine Jinqi Jiangtang Tablet. J Ethnopharmacol. 2015;164:210–22.PubMedCrossRef
40.
den Hartigh LJ, Han CY, Wang S, Omer M, Chait A. 10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species. J Lipid Res. 2013;54(11):2964–78.CrossRef
41.
Jackson RL, Taunton OD, Morrisett JD, Gotto AM Jr. The role of dietary polyunsaturated fat in lowering blood cholesterol in man. Circ Res. 1978;42(4):447–53.PubMedCrossRef
42.
Demetz E, Schroll A, Auer K, Heim C, Patsch JR, Eller P, Theurl M, Theurl I, Theurl M, Seifert M, et al. The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism. Cell Metab. 2014;20(5):787–98.PubMedPubMedCentralCrossRef
43.
Li JJ, Huang CJ, Xie D. Anti-obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. Mol Nutr Food Res. 2008;52(6):631–45.PubMedCrossRef
44.
Mason RP, Jacob RF. Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism. Biochim Biophys Acta. 2015;1848(2):502–9.PubMedCrossRef
45.
Rink F, Bauer E, Eklund M, Mosenthin R. The effect of betaine on in vitro fermentation of carbohydrate and protein combinations under osmotic stress in pigs. J Sci Food Agric. 2012;92(12):2486–93.PubMedCrossRef
46.
McIntosh FM, Shingfield KJ, Devillard E, Russell WR, Wallace RJ. Mechanism of conjugated linoleic acid and vaccenic acid formation in human faecal suspensions and pure cultures of intestinal bacteria. Microbiology. 2009;155(Pt 1):285–94.PubMedCrossRef
47.
Piazzi G, D’Argenio G, Prossomariti A, Lembo V, Mazzone G, Candela M, Biagi E, Brigidi P, Vitaglione P, Fogliano V, et al. Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota. Int J Cancer. 2014;135(9):2004–13.PubMedCrossRef
48.
49.
Dardente H, Fortier EE, Martineau V, Cermakian N. Cryptochromes impair phosphorylation of transcriptional activators in the clock: a general mechanism for circadian repression. Biochem J. 2007;402(3):525–36.PubMedPubMedCentralCrossRef
50.
Masri S, Rigor P, Cervantes M, Ceglia N, Sebastian C, Xiao C, Roqueta-Rivera M, Deng C, Osborne TF, Mostoslavsky R, et al. Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell. 2014;158(3):659–72.PubMedPubMedCentralCrossRef
51.
Eeckhaut V, Wang J, Van Parys A, Haesebrouck F, Joossens M, Falony G, Raes J, Ducatelle R, Van Immerseel F. The probiotic Butyricicoccus pullicaecorum reduces feed conversion and protects from potentially harmful intestinal microorganisms and necrotic enteritis in broilers. Front Microbiol. 2016;7:1416.PubMedPubMedCentralCrossRef
52.
Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, Raisen C, Goulding D, Rad R, Schreiber F, Brandt C, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog. 2012;8(10):e1002995.PubMedPubMedCentralCrossRef
53.
Schubert AM, Rogers MA, Ring C, Mogle J, Petrosino JP, Young VB, Aronoff DM, Schloss PD. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. MBio. 2014;5(3):e01021-01014.PubMedPubMedCentralCrossRef
54.
Zhang J, Guo Z, Xue Z, Sun Z, Zhang M, Wang L, Wang G, Wang F, Xu J, Cao H, et al. A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities. ISME J. 2015;9(9):1979–90.PubMedPubMedCentralCrossRef
55.
De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107(33):14691–6.PubMedPubMedCentralCrossRef
56.
Ridlon JM, Ikegawa S, Alves JM, Zhou B, Kobayashi A, Iida T, Mitamura K, Tanabe G, Serrano M, De Guzman A, et al. Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens. J Lipid Res. 2013;54(9):2437–49.PubMedPubMedCentralCrossRef
57.
Greathouse KL, Harris CC, Bultman SJ. Dysfunctional families: Clostridium scindens and secondary bile acids inhibit the growth of Clostridium difficile. Cell Metab. 2015;21(1):9–10.PubMedCrossRef
58.
59.
Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Rasanen SM, Lee S, Mancina RM, Bergentall M, Pietilainen KH, et al. An integrated understanding of the rapid metabolic benefits of a carbohydrate-restricted diet on hepatic steatosis in humans. Cell Metab. 2018;27(3):559-571.e555.PubMedPubMedCentralCrossRef
Metadata
Title
Obese rats intervened with Rhizoma coptidis revealed differential gene expression and microbiota by serum metabolomics
Authors
Yanhua Ji
Kexin Luo
Jiri Mutu Zhang
Peng Ni
Wangping Xiong
Xiaoquan Luo
Guoliang Xu
Hongning Liu
Zhijun Zeng
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-021-03382-3

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