Effects and Mechanism of Chlorogenic Acid on Weight Loss

Author(s): Yanchun Zhong, Yueling Ding, Laiqing Li, Meina Ge, Guangguo Ban, Hongxia Yang, Jun Dai, Licheng Zhang*

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 11 , 2020


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Graphical Abstract:


Abstract:

Background: Chlorogenic Acid (CA) has diverse, recognized health effects.

Objective: This study aimed to explore the effects of CA on fat reduction and the underlying mechanism of these effects.

Materials and Methods: First, we established a Monosodium Glutamate (MSG)-induced obesity mouse model and subjected the mice to 4 weeks of CA gavage. Then, we established an oleic acidinduced model of human fatty liver in HepG2 cells, and administered a CA intervention to the cells for 48 h. Finally, we used Oil red O staining, biochemical detection kits, RT-PCR and Western blot analysis to evaluate the effects of CA on fat reduction and on related pathways.

Results: The CA treatment could reduce fat accumulation in the liver and reduce blood lipid levels. In addition, CA decreased the mRNA and protein levels of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α) and Uncoupling Protein 1 (UCP1) in the MSG-induced obesity mouse model and the oleic acid-induced HepG2 cells.

Conclusion: Based on the above results, we deduced that CA could reduce body weight and fat deposition in vitro and in vivo and that the mechanism may be related to the PGC-1α/UCP-1 pathway. CA can be developed as a drug to lower blood lipids and to treat obesity.

Keywords: Chlorogenic acid, fat deposition, obesity, PGC-1α/UCP-1 pathway, monosodium glutamate.

[1]
Fox, C.K.; Ryder, J.R.; Gross, A.C.; Kelly, A.S. Severe obesity in the pediatric population: Current concepts in clinical care. Curr. Obes. Rep., 2019, 8, 201–209.
[2]
Chen, C.M. Overview of obesity in Mainland China. Obes. Rev., 2008, 9(Suppl. 1), 14-21.
[http://dx.doi.org/10.1111/j.1467-789X.2007.00433.x] [PMID: 18307694]
[3]
Haslam, D.W.; James, W.P. Obesity. Lancet, 2005, 366(9492), 1197-1209.
[http://dx.doi.org/10.1016/S0140-6736(05)67483-1] [PMID: 16198769]
[4]
Islam, M.S.; Hossain, M.A. Obesity and cardiovascular disase risk factors, paradox and impact of weight loss. J. Am. Coll. Cardiol., 2017, 53, 1925-1932.
[http://dx.doi.org/10.3329/kyamcj.v5i1.32320]
[5]
Porter, J.A.; Raebel, M.A.; Conner, D.A.; Lanty, F.A.; Vogel, E.A.; Gay, E.C.; Merenich, J.A. The long-term outcomes of sibutramine effectiveness on weight (LOSE Weight) study: Evaluating the role of drug therapy within a weight management program in a group-model health maintenance organization. Am. J. Manag. Care, 2004, 10(6), 369-376.
[http://dx.doi.org/dx. doi.org/10.1097/00001888-200406000-00022] [PMID: 15209480]
[6]
Domecq, J.P.; Prutsky, G.; Wang, Z.; Elraiyah, T.; Brito, J.P.; Mauck, K.; Lababidi, M.H.; Leppin, A.; Fidahussein, S.; Prokop, L.J.; Montori, V.M.; Murad, M.H. Drugs commonly associated with weight change: Umbrella systematic review and meta-analysis (Protocol). Syst. Rev., 2012, 1, 44-50.
[http://dx.doi.org/10.1186/2046-4053-1-44] [PMID: 23020969]
[7]
Olthof, M.R.; Hollman, P.C.; Buijsman, M.N.; van Amelsvoort, J.M.; Katan, M.B. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J. Nutr., 2003, 133(6), 1806-1814.
[http://dx.doi.org/10.1093/jn/133.6.1806] [PMID: 12771321]
[8]
He, X.; Wang, J.; Li, M.; Hao, D.; Yang, Y.; Zhang, C.; He, R.; Tao, R. Eucommia ulmoides Oliv.: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine. J. Ethnopharmacol., 2014, 151(1), 78-92.
[http://dx.doi.org/10.1016/j.jep.2013.11.023] [PMID: 24296089]
[9]
dos Santos, M.D.; Almeida, M.C.; Lopes, N.P.; de Souza, G.E. Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid. Biol. Pharm. Bull., 2006, 29(11), 2236-2240.
[http://dx.doi.org/10.1248/bpb.29.2236] [PMID: 17077520]
[10]
Rodriguez de Sotillo, D.V.; Hadley, M. Chlorogenic acid modifies plasma and liver concentrations of: cholesterol, triacylglycerol, and minerals in (fa/fa) Zucker rats. J. Nutr. Biochem., 2002, 13(12), 717-726.
[http://dx.doi.org/10.1016/S0955-2863(02)00231-0 ] [PMID: 12550056]
[11]
Cho, A.S.; Jeon, S.M.; Kim, M.J.; Yeo, J.; Seo, K.I.; Choi, M.S.; Lee, M.K. Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice. Food. Chem. Toxicol., 2010, 48, 0-943.
[http://dx.doi.org/10.1016/j.fct.2010.01.003 PMID: 20064576]
[12]
Wan, C.W.; Wong, C.N.; Pin, W.K.; Wong, M.H.; Kwok, C.Y.; Chan, R.Y.; Yu, P.H.; Chan, S.W. Chlorogenic acid exhibits cholesterol lowering and fatty liver attenuating properties by up-regulating the gene expression of PPAR-α in hypercholesterolemic rats induced with a high-cholesterol diet. Phytother. Res., 2013, 27(4), 545-551.
[http://dx.doi.org/10.1002/ptr.4751] [PMID: 22674675]
[13]
Sasaki, Y.; Suzuki, W.; Shimada, T.; Iizuka, S.; Nakamura, S.; Nagata, M.; Fujimoto, M.; Tsuneyama, K.; Hokao, R.; Miyamoto, K.; Aburada, M. Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice. Life Sci., 2009, 85(13-14), 490-498.
[http://dx.doi.org/10.1016/j.lfs.2009.07.017] [PMID: 19683013]
[14]
Hernández Bautista, R.J.; Mahmoud, A.M.; Königsberg, M.; López Díaz Guerrero, N.E. Obesity: Pathophysiology, monosodium glutamate-induced model and anti-obesity medicinal plants. Biomed. Pharmacother., 2019, 111, 503-516.
[http://dx.doi.org/10.1016/j.biopha.2018.12.108] [PMID: 30597304]
[15]
Guzik, T.J.; Mangalat, D.; Korbut, R. Adipocytokines - novel link between inflammation and vascular function? J. Physiol. Pharmacol., 2006, 57(4), 505-528.
[http://dx.doi.org/10.2170/physiolsci.TN009306] [PMID: 17229978]
[16]
Yang, J.; Lee, N. Skin permeation and antiinflammatory effects of hydrolysis of Gardeniae fructus. J. Pharm. Investig., 2004, 34, 115-123.
[http://dx.doi.org/10.4333/KPS.2004.34.2.115]
[17]
Ma, Y.; Gao, M.; Liu, D. Chlorogenic acid improves high fat diet-induced hepatic steatosis and insulin resistance in mice. Pharm. Res., 2015, 32(4), 1200-1209.
[http://dx.doi.org/10.1007/s11095-014-1526-9] [PMID: 25248334]
[18]
Zheng, G.; Qiu, Y.; Zhang, Q.F.; Li, D. Chlorogenic acid and caffeine in combination inhibit fat accumulation by regulating hepatic lipid metabolism-related enzymes in mice. Br. J. Nutr., 2014, 112(6), 1034-1040.
[http://dx.doi.org/10.1017/S0007114514001652] [PMID: 25201308]
[19]
Barroso, W.A.; Victorino, V.J.; Jeremias, I.C.; Petroni, R.C.; Ariga, S.K.K.; Salles, T.A.; Barbeiro, D.F.; de Lima, T.M.; de Souza, H.P. High-fat diet inhibits PGC-1α suppressive effect on NFκB signaling in hepatocytes. Eur. J. Nutr., 2018, 57(5), 1891-1900.
[http://dx.doi.org/10.1007/s00394-017-1472-5] [PMID: 28540526]
[20]
Wilson-Fritch, L.; Nicoloro, S.; Chouinard, M.; Lazar, M.A.; Chui, P.C.; Leszyk, J.; Straubhaar, J.; Czech, M.P.; Corvera, S. Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J. Clin. Invest., 2004, 114(9), 1281-1289.
[http://dx.doi.org/10.1172/JCI21752] [PMID: 15520860]
[21]
Wrann, C.D.; White, J.P.; Salogiannnis, J.; Laznik-Bogoslavski, D.; Wu, J.; Ma, D.; Lin, J.D.; Greenberg, M.E.; Spiegelman, B.M. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab., 2013, 18(5), 649-659.
[http://dx.doi.org/10.1016/j.cmet.2013.09.008] [PMID: 24120943]
[22]
Kleiner, S.; Mepani, R.J.; Laznik, D.; Jurczak, M.J.; Jornayvaz, F.R.; Estall, J.L.; Bhowmick, D.C.; Shulman, G.I.; Spiegelman, B.M. Development of insulin resistance in mice lacking PGC-1α in adipose tissues. Proc. Natl. Acad. Sci. USA, 2012, 109, 9635-9640.
[http://dx.doi.org/dx. doi.org/10.1073/pnas.1207287109 ] [PMID: 22645355]
[23]
Zhou, Y.; Ruan, Z.; Zhou, L.; Shu, X.; Sun, X.; Mi, S.; Yang, Y.; Yin, Y. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation. Biochem. Biophys. Res. Commun., 2016, 469(4), 1083-1089.
[http://dx.doi.org/10.1016/j.bbrc.2015.12.094] [PMID: 26740181]
[24]
Villarroya, F.; Peyrou, M.; Giralt, M. Transcriptional regulation of the uncoupling protein-1 gene. Biochimie, 2017, 134, 86-92.
[http://dx.doi.org/10.1016/j.biochi.2016.09.017] [PMID: 27693079]
[25]
Ravaud, C. Resveratrol and HIV, rotease inhibitors control UCP1 expression through opposite effects on p38 MAPK phosphorylation in human adipocytes. J. Cellul. Physiol. 2019, 6
[http://dx.doi.org/10.1002/jcp.29032]
[26]
Arias, N.; Picó, C.; Teresa Macarulla, M.; Oliver, P.; Miranda, J.; Palou, A.; Portillo, M.P. A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet. Obesity (Silver Spring), 2017, 25(1), 111-121.
[http://dx.doi.org/10.1002/oby.21706] [PMID: 27874268]
[27]
Fujikawa, T.; Hirata, T.; Hosoo, S.; Nakajima, K.; Wada, A.; Yurugi, Y.; Soya, H.; Matsui, T.; Yamaguchi, A.; Ogata, M.; Nishibe, S. Asperuloside stimulates metabolic function in rats across several organs under high-fat diet conditions, acting like the major ingredient of Eucommia leaves with anti-obesity activity. J. Nutr. Sci., 2012, 1, e10-e20.
[http://dx.doi.org/10.1017/jns.2012.12] [PMID: 25191539]
[28]
Fromme, T.; Kleigrewe, K.; Dunkel, A.; Retzler, A.; Li, Y.; Maurer, S.; Fischer, N.; Diezko, R.; Kanzleiter, T.; Hirschberg, V.; Hofmann, T.; Klingenspor, M. Degradation of brown adipocyte purine nucleotides regulates uncoupling protein 1 activity. Mol. Metab., 2018, 8, 77-85.
[http://dx.doi.org/10.1016/j.molmet.2017.12.010] [PMID: 29310935]
[29]
Yan, H.; Gao, Y.Q.; Zhang, Y.; Wang, H.; Liu, G.S.; Lei, J.Y. Chlorogenic acid alleviates autophagy and insulin resistance by suppressing JNK pathway in a rat model of nonalcoholic fatty liver disease. J. Biosci., 2018, 43(2), 287-294.
[http://dx.doi.org/10.1007/s12038-018-9746-5] [PMID: 29872017]
[30]
Zheng, S.Q.; Huang, X.B.; Xing, T.K.; Ding, A.J.; Wu, G.S.; Luo, H.R. Chlorogenic acid extends the lifespan of Caenorhabditis elegans via insulin/IGF-1 signaling pathway. J. Gerontol. A Biol. Sci. Med. Sci., 2017, 72(4), 464-472.
[http://dx.doi.org/10.1093/gerona/glw105] [PMID: 27378235]
[31]
Muraoka, M.; Fukushima, A.; Viengchareun, S.; Lombès, M.; Kishi, F.; Miyauchi, A.; Kanematsu, M.; Doi, J.; Kajimura, J.; Nakai, R.; Uebi, T.; Okamoto, M.; Takemori, H. Involvement of SIK2/TORC2 signaling cascade in the regulation of insulin-induced PGC-1alpha and UCP-1 gene expression in brown adipocytes. Am. J. Physiol. Endocrinol. Metab., 2009, 296(6), E1430-E1439.
[http://dx.doi.org/10.1152/ajpendo.00024.2009] [PMID: 19351809]


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Article Details

VOLUME: 21
ISSUE: 11
Year: 2020
Published on: 20 September, 2020
Page: [1099 - 1106]
Pages: 8
DOI: 10.2174/1389201021666200318124922
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