Recent Development on Anti-Obesity Compounds and their Mechanisms of Action: A Review

Author(s): Yixing Qiu, Huanghe Yu, Rong Zeng, Shiyin Guo, Muhammad Daniyal, Zeyu Deng, Aibing Wang*, Wei Wang*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 21 , 2020

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Obesity, associated with a series of complications such as diabetes, hypertension, and heart disease, is a great threat to human health and leads to increased morbidity and mortality. Despite the presence of anti-obesity agents on the market, the application of these drugs is limited because of their typical side effects. More effective and safe weight-loss drugs are being pursued by many researchers, correspondingly, growing small molecules and natural products with anti-obesity effects have been identified and the molecular mechanisms underlying the action of the novel and known compounds have at least partially been revealed. Therefore, the field does witness great progress year by year. In this review, we intend to provide a comprehensive and updated view on the known and novel compounds which possess anti-obesity effects and further classify them according to the molecular mechanisms of their actions in regulating the major anti-obesity pathways.

Keywords: Obesity, active compounds, mechanisms of action, lipid metabolism and energy expenditure, adipocyte differentiation, insulin resistance, chronic inflammation, gut microorganism.

Skinner, A.C.; Ravanbakht, S.N.; Skelton, J.A.; Perrin, E.M.; Armstrong, S.C. Prevalence of obesity and severe obesity in US children, 1999-2016. Pediatrics, 2018, 141(3), e20173459
[] [PMID: 29483202]
Hales, C.M.; Carroll, M.D.; Fryar, C.D.; Ogden, C.L. Prevalence of obesity among adults and youth: United States, 2015-2016. NCHS Data Brief, 2017, (288), 1-8.
[PMID: 29155689]
Lobstein, T.; Jackson-Leach, R.; Moodie, M.L.; Hall, K.D.; Gortmaker, S.L.; Swinburn, B.A.; James, W.P.T.; Wang, Y.; McPherson, K. Child and adolescent obesity: part of a bigger picture. Lancet, 2015, 385(9986), 2510-2520.
[] [PMID: 25703114]
Ng, M.; Fleming, T.; Robinson, M.; Thomson, B.; Graetz, N.; Margono, C.; Mullany, E.C.; Biryukov, S.; Abbafati, C.; Abera, S.F.; Abraham, J.P.; Abu-Rmeileh, N.M.; Achoki, T.; AlBuhairan, F.S.; Alemu, Z.A.; Alfonso, R.; Ali, M.K.; Ali, R.; Guzman, N.A.; Ammar, W.; Anwari, P.; Banerjee, A.; Barquera, S.; Basu, S.; Bennett, D.A.; Bhutta, Z.; Blore, J.; Cabral, N.; Nonato, I.C.; Chang, J.C.; Chowdhury, R.; Courville, K.J.; Criqui, M.H.; Cundiff, D.K.; Dabhadkar, K.C.; Dandona, L.; Davis, A.; Dayama, A.; Dharmaratne, S.D.; Ding, E.L.; Durrani, A.M.; Esteghamati, A.; Farzadfar, F.; Fay, D.F.; Feigin, V.L.; Flaxman, A.; Forouzanfar, M.H.; Goto, A.; Green, M.A.; Gupta, R.; Hafezi-Nejad, N.; Hankey, G.J.; Harewood, H.C.; Havmoeller, R.; Hay, S.; Hernandez, L.; Husseini, A.; Idrisov, B.T.; Ikeda, N.; Islami, F.; Jahangir, E.; Jassal, S.K.; Jee, S.H.; Jeffreys, M.; Jonas, J.B.; Kabagambe, E.K.; Khalifa, S.E.; Kengne, A.P.; Khader, Y.S.; Khang, Y.H.; Kim, D.; Kimokoti, R.W.; Kinge, J.M.; Kokubo, Y.; Kosen, S.; Kwan, G.; Lai, T.; Leinsalu, M.; Li, Y.; Liang, X.; Liu, S.; Logroscino, G.; Lotufo, P.A.; Lu, Y.; Ma, J.; Mainoo, N.K.; Mensah, G.A.; Merriman, T.R.; Mokdad, A.H.; Moschandreas, J.; Naghavi, M.; Naheed, A.; Nand, D.; Narayan, K.M.; Nelson, E.L.; Neuhouser, M.L.; Nisar, M.I.; Ohkubo, T.; Oti, S.O.; Pedroza, A.; Prabhakaran, D.; Roy, N.; Sampson, U.; Seo, H.; Sepanlou, S.G.; Shibuya, K.; Shiri, R.; Shiue, I.; Singh, G.M.; Singh, J.A.; Skirbekk, V.; Stapelberg, N.J.; Sturua, L.; Sykes, B.L.; Tobias, M.; Tran, B.X.; Trasande, L.; Toyoshima, H.; van de Vijver, S.; Vasankari, T.J.; Veerman, J.L.; Velasquez-Melendez, G.; Vlassov, V.V.; Vollset, S.E.; Vos, T.; Wang, C.; Wang, X.; Weiderpass, E.; Werdecker, A.; Wright, J.L.; Yang, Y.C.; Yatsuya, H.; Yoon, J.; Yoon, S.J.; Zhao, Y.; Zhou, M.; Zhu, S.; Lopez, A.D.; Murray, C.J.; Gakidou, E. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2014, 384(9945), 766-781.
[] [PMID: 24880830]
Popkin, B.M.; Adair, L.S.; Ng, S.W. Global nutrition transition and the pandemic of obesity in developing countries. Nutr. Rev., 2012, 70(1), 3-21.
[] [PMID: 22221213]
Poobalan, A.; Aucott, L. Obesity among young adults in developing countries: a systematic overview. Curr. Obes. Rep., 2016, 5(1), 2-13.
[] [PMID: 26883372]
Jia, P.; Xue, H.; Zhang, J.; Wang, Y. Time trend and demographic and geographic disparities in child-hood obesity prevalence in china-evidence from twenty years of longitudinal data. Int. J. Environ. Res. Public Health, 2017, 14(4), 369.
[] [PMID: 28362361]
Zhang, J.; Wang, H.; Wang, Z.; Du, W.; Su, C.; Zhang, J.; Jiang, H.; Jia, X.; Huang, F.; Ouyang, Y.; Wang, Y.; Zhang, B. Prevalence and stabilizing trends in overweight and obesity among children and adolescents in China, 2011-2015. BMC Public Health, 2018, 18(1), 571.
[] [PMID: 29716560]
Witkamp, R.F. 3.15-Biologically active compounds in food products and their effects on obesity and diabetes. Comprehensive Natural Products II, 2010, 46(1), 509-545.
Kumar, R.B.; Aronne, L.J. Review of multimodal therapies for obesity treatment: Including dietary, counseling strategies, and pharmacologic interventions. Tech. Gastrointest. Endosc., 2017, 19(1), 12-17.
Tilg, H.; Hotamisligil, G.S. Nonalcoholic fatty liver disease: Cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology, 2006, 131(3), 934-945.
[] [PMID: 16952562]
Zhang, W.L.; Zhu, L.; Jiang, J.G. Active ingredients from natural botanicals in the treatment of obesity. Obes. Rev., 2014, 15(12), 957-967.
[] [PMID: 25417736]
Martel, J.; Ojcius, D.M.; Chang, C-J.; Lin, C-S.; Lu, C-C.; Ko, Y-F.; Tseng, S-F.; Lai, H-C.; Young, J.D. Anti-obesogenic and antidiabetic effects of plants and mushrooms. Nat. Rev. Endocrinol., 2017, 13(3), 149-160.
[] [PMID: 27636731]
Yun, J.W. Possible anti-obesity therapeutics from nature--a review. Phytochemistry, 2010, 71(14-15), 1625-1641.
[] [PMID: 20732701]
Sinha, R. Role of addiction and stress neurobiology on food intake and obesity. Biol. Psychol., 2018, 131, 5-13.
[] [PMID: 28479142]
Redman, L.M.; Ravussin, E. Lorcaserin for the treatment of obesity. Drugs Today (Barc), 2010, 46(12), 901-910.
[] [PMID: 21589947]
Heal, D.J.; Smith, S.L.; Fisas, A.; Codony, X.; Buschmann, H. Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders. Pharmacol. Ther., 2008, 117(2), 207-231.
[] [PMID: 18068807]
Thomsen, W.J.; Grottick, A.J.; Menzaghi, F.; Reyes-Saldana, H.; Espitia, S.; Yuskin, D.; Whelan, K.; Martin, M.; Morgan, M.; Chen, W.; Al-Shamma, H.; Smith, B.; Chalmers, D.; Behan, D. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J. Pharmacol. Exp. Ther., 2008, 325(2), 577-587.
[] [PMID: 18252809]
Smith, S.R.; Weissman, N.J.; Anderson, C.M.; Sanchez, M.; Chuang, E.; Stubbe, S.; Bays, H.; Shanahan, W.R. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N. Engl. J. Med., 2010, 363(3), 245-256.
[] [PMID: 20647200]
Smith, S.R.; Prosser, W.A.; Donahue, D.J.; Morgan, M.E.; Anderson, C.M.; Shanahan, W.R. APD356-004 Study Group. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity (Silver Spring), 2009, 17(3), 494-503.
[] [PMID: 19057523]
Martin, C.K.; Redman, L.M.; Zhang, J.; Sanchez, M.; Anderson, C.M.; Smith, S.R.; Ravussin, E. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J. Clin. Endocrinol. Metab., 2011, 96(3), 837-845.
[] [PMID: 21190985]
Yang, H.Y.; Tae, J.; Seo, Y.W.; Kim, Y.J.; Im, H.Y.; Choi, G.D.; Cho, H.; Park, W.K.; Kwon, O.S.; Cho, Y.S.; Ko, M.; Jang, H.; Lee, J.; Choi, K.; Kim, C.H.; Lee, J.; Pae, A.N. Novel pyrimidoazepine analogs as serotonin 5-HT(2A) and 5-HT(2C) receptor ligands for the treatment of obesity. Eur. J. Med. Chem., 2013, 63(5), 558-569.
[] [PMID: 23537943]
Wren, A.M.; Seal, L.J.; Cohen, M.A.; Brynes, A.E.; Frost, G.S.; Murphy, K.G.; Dhillo, W.S.; Ghatei, M.A.; Bloom, S.R. Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab., 2001, 86(12), 5992.
[] [PMID: 11739476]
Takahashi, B.; Funami, H.; Iwaki, T.; Maruoka, H.; Shibata, M.; Koyama, M.; Nagahira, A.; Kamiide, Y.; Kanki, S.; Igawa, Y.; Muto, T. Orally active ghrelin receptor inverse agonists and their actions on a rat obesity model. Bioorg. Med. Chem., 2015, 23(15), 4792-4803.
[] [PMID: 26100441]
Kroog, G.S.; Jensen, R.T.; Battey, J.F. Mammalian bombesin receptors. Med. Res. Rev., 1995, 15(5), 389-417.
[] [PMID: 8531502]
Guan, X.M.; Chen, H.; Dobbelaar, P.H.; Dong, Y.; Fong, T.M.; Gagen, K.; Gorski, J.; He, S.; Howard, A.D.; Jian, T.; Jiang, M.; Kan, Y.; Kelly, T.M.; Kosinski, J.; Lin, L.S.; Liu, J.; Marsh, D.J.; Metzger, J.M.; Miller, R.; Nargund, R.P.; Palyha, O.; Shearman, L.; Shen, Z.; Stearns, R.; Strack, A.M.; Stribling, S.; Tang, Y.S.; Wang, S.P.; White, A.; Yu, H.; Reitman, M.L. Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity. Cell Metab., 2010, 11(2), 101-112.
[] [PMID: 20096642]
Ohki-Hamazaki, H.; Watase, K.; Yamamoto, K.; Ogura, H.; Yamano, M.; Yamada, K.; Maeno, H.; Imaki, J.; Kikuyama, S.; Wada, E.; Wada, K. Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature, 1997, 390(6656), 165-169.
[] [PMID: 9367152]
Chobanian, H.R.; Guo, Y.; Liu, P.; Chioda, M.; Lanza, T.J., Jr; Chang, L.; Kelly, T.M.; Kan, Y.; Palyha, O.; Guan, X.M.; Marsh, D.J.; Metzger, J.M.; Gorski, J.N.; Raustad, K.; Wang, S.P.; Strack, A.M.; Miller, R.; Pang, J.; Madeira, M.; Lyons, K.; Dragovic, J.; Reitman, M.L.; Nargund, R.P.; Lin, L.S. Discovery of MK-7725, A potent, selective bombesin receptor subtype-3 agonist for the treatment of obesity. ACS Med. Chem. Lett., 2012, 3(3), 252-256.
[] [PMID: 24900461]
Liu, J.; He, S.; Jian, T.; Dobbelaar, P.H.; Sebhat, I.K.; Lin, L.S.; Goodman, A.; Guo, C.; Guzzo, P.R.; Hadden, M.; Henderson, A.J.; Pattamana, K.; Ruenz, M.; Sargent, B.J.; Swenson, B.; Yet, L.; Tamvakopoulos, C.; Peng, Q.; Pan, J.; Kan, Y.; Palyha, O.; Kelly, T.M.; Guan, X.M.; Howard, A.D.; Marsh, D.J.; Metzger, J.M.; Reitman, M.L.; Wyvratt, M.J.; Nargund, R.P. Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity. Bioorg. Med. Chem. Lett., 2010, 20(7), 2074-2077.
[] [PMID: 20219372]
Kowalski, T.J.; McBriar, M.D. Therapeutic potential of melanin-concentrating hormone-1 receptor antagonists for the treatment of obesity. Expert Opin. Investig. Drugs, 2004, 13(9), 1113-1122.
[] [PMID: 15330743]
Ludwig, D.S.; Tritos, N.A.; Mastaitis, J.W.; Kulkarni, R.; Kokkotou, E.; Elmquist, J.; Lowell, B.; Flier, J.S.; Maratos-Flier, E. Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J. Clin. Invest., 2001, 107(3), 379-386.
[] [PMID: 11160162]
Mihalic, J.T.; Chen, X.; Fan, P.; Chen, X.; Fu, Y.; Liang, L.; Reed, M.; Tang, L.; Chen, J.L.; Jaen, J.; Li, L.; Dai, K. Discovery of a novel series of melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity. Bioorg. Med. Chem. Lett., 2011, 21(23), 7001-7005.
[] [PMID: 22019296]
Schober, G.; Arnold, M.; Birtles, S.; Buckett, L.K.; Pacheco-López, G.; Turnbull, A.V.; Langhans, W.; Mansouri, A. Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats. J. Lipid Res., 2013, 54(5), 1369-1384.
[] [PMID: 23449193]
Qian, Y.; Wertheimer, S.J.; Ahmad, M.; Cheung, A.W-H.; Firooznia, F.; Hamilton, M.M.; Hayden, S.; Li, S.; Marcopulos, N.; McDermott, L.; Tan, J.; Yun, W.; Guo, L.; Pamidimukkala, A.; Chen, Y.; Huang, K.S.; Ramsey, G.B.; Whittard, T.; Conde-Knape, K.; Taub, R.; Rondinone, C.M.; Tilley, J.; Bolin, D. Discovery of orally active carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamide as potent diacylglycerol acyltransferase-1 inhibitors for the potential treatment of obesity and diabetes. J. Med. Chem., 2011, 54(7), 2433-2446.
[] [PMID: 21413799]
Schober, G.; Arnold, M.; Birtles, S.; Buckett, L.; Turnbull, A.V.; Langhans, W. Diacylglycerol acyl-transferase-1 (DGAT-1) inhibition reduces food intake and blunts postprandial increases in circulating fat metabolites in high fat diet (HFD)-fed rats. Appetite, 2010, 54(3), 674-674.
Saely, C.H.; Geiger, K.; Drexel, H. Brown versus white adipose tissue: a mini-review. Gerontology, 2012, 58(1), 15-23.
[] [PMID: 21135534]
Enerbäck, S. Brown adipose tissue in humans. Int. J. Obes., 2010, 34(Suppl. 1), S43-S46.
[] [PMID: 20935666]
Fujioka, S.; Matsuzawa, Y.; Tokunaga, K.; Tarui, S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism, 1987, 36(1), 54-59.
[] [PMID: 3796297]
Solini, A.; Bonora, E.; Bonadonna, R.; Castellino, P.; DeFronzo, R.A. Protein metabolism in human obesity: relationship with glucose and lipid metabolism and with visceral adipose tissue. J. Clin. Endocrinol. Metab., 1997, 82(8), 2552-2558.
[] [PMID: 9253333]
Yamamoto, T.; Yamaguchi, H.; Miki, H.; Kitamura, S.; Nakada, Y.; Aicher, T.D.; Pratt, S.A.; Kato, K. A novel coenzyme A:diacylglycerol acyltransferase 1 inhibitor stimulates lipid metabolism in muscle and lowers weight in animal models of obesity. Eur. J. Pharmacol., 2011, 650(2-3), 663-672.
[] [PMID: 21034741]
Yamamoto, T.; Yamaguchi, H.; Miki, H.; Shimada, M.; Nakada, Y.; Ogino, M.; Asano, K.; Aoki, K.; Tamura, N.; Masago, M.; Kato, K. Coenzyme A: diacylglycerol acyltransferase 1 inhibitor ameliorates obesity, liver steatosis, and lipid metabolism abnormality in KKAy mice fed high-fat or high-carbohydrate diets. Eur. J. Pharmacol., 2010, 640(1-3), 243-249.
[] [PMID: 20478303]
Fox, B.M.; Furukawa, N.; Hao, X.; Iio, K.; Inaba, T.; Jackson, S.M.; Kayser, F.; Labelle, M.; Li, K.; Matsui, T. Fused bicyclic nitrogen-containing heterocycles; Google Patents, 2007.
Tsuda, N.; Kumadaki, S.; Higashi, C.; Ozawa, M.; Shinozaki, M.; Kato, Y.; Hoshida, K.; Kikuchi, S.; Nakano, Y.; Ogawa, Y.; Furusako, S. Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice. PLoS One, 2014, 9(11), e112027-e112027.
[] [PMID: 25405858]
Desvergne, B.; Wahli, W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev., 1999, 20(5), 649-688.
[PMID: 10529898]
Girroir, E.E.; Hollingshead, H.E.; He, P.; Zhu, B.; Perdew, G.H.; Peters, J.M. Quantitative expression patterns of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) protein in mice. Biochem. Biophys. Res. Commun., 2008, 371(3), 456-461.
[] [PMID: 18442472]
Braissant, O.; Foufelle, F.; Scotto, C.; Dauça, M.; Wahli, W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology, 1996, 137(1), 354-366.
[] [PMID: 8536636]
Szkudelska, K.; Szkudelski, T. Resveratrol, obesity and diabetes. Eur. J. Pharmacol., 2010, 635(1-3), 1-8.
[] [PMID: 20303945]
Szkudelski, T.; Szkudelska, K. Anti-diabetic effects of resveratrol. Ann. N. Y. Acad. Sci., 2011, 1215(1), 34-39.
[] [PMID: 21261639]
Aguirre, L.; Fernández-Quintela, A.; Arias, N.; Portillo, M.P. Resveratrol: anti-obesity mechanisms of action. Molecules, 2014, 19(11), 18632-18655.
[] [PMID: 25405284]
Lasa, A.; Churruca, I.; Eseberri, I.; Andrés-Lacueva, C.; Portillo, M.P. Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol. Nutr. Food Res., 2012, 56(10), 1559-1568.
[] [PMID: 22945685]
Fernández-Quintela, A.; Carpéné, C.; Fernández, M.; Aguirre, L.; Milton-Laskibar, I.; Contreras, J.; Portillo, M.P. Anti-obesity effects of resveratrol: comparison between animal models and humans. J. Physiol. Biochem., 2016, 73(3), 417-429.
[] [PMID: 27981508]
Timmers, S.; Konings, E.; Bilet, L.; Houtkooper, R.H.; van de Weijer, T.; Goossens, G.H.; Hoeks, J.; van der Krieken, S.; Ryu, D.; Kersten, S.; Moonen-Kornips, E.; Hesselink, M.K.C.; Kunz, I.; Schrauwen-Hinderling, V.B.; Blaak, E.; Auwerx, J.; Schrauwen, P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab., 2011, 14(5), 612-622.
[] [PMID: 22055504]
Ghadieh, H.E.; Smiley, Z.N.; Kopfman, M.W.; Najjar, M.G.; Hake, M.J.; Najjar, S.M. Chlorogenic acid/chromium supplement rescues diet-induced insulin resistance and obesity in mice. Nutr. Metab. (Lond.), 2015, 12(1), 19.
[] [PMID: 26045713]
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(3), 937-943.
[] [PMID: 20064576]
Diamant, M.; Heine, R.J. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. Drugs, 2003, 63(13), 1373-1405.
[] [PMID: 12825962]
Saltiel, A.R.; Olefsky, J.M. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes, 1996, 45(12), 1661-1669.
[] [PMID: 8922349]
Bhattarai, B.R.; Kafle, B.; Hwang, J-S.; Ham, S.W.; Lee, K-H.; Park, H.; Han, I-O.; Cho, H. Novel thiazolidinedione derivatives with anti-obesity effects: dual action as PTP1B inhibitors and PPAR-γ activators. Bioorg. Med. Chem. Lett., 2010, 20(22), 6758-6763.
[] [PMID: 20850970]
Tercel, M.; Marnane, R.N.; Tatnell, M.A.; Stevenson, R.J.; Halim, A.; Lu, G.L.; Duchesnes, C.; Truong, M.; Denny, W.A.; Wilson, W.R.; Mountjoy, K.G. An indoline-derived compound that markedly reduces mouse body weight. Int. J. Obes., 2013, 37(5), 685-692.
[] [PMID: 22732909]
Shimano, H.; Yahagi, N.; Amemiya-Kudo, M.; Hasty, A.H.; Osuga, J.; Tamura, Y.; Shionoiri, F.; Iizuka, Y.; Ohashi, K.; Harada, K.; Gotoda, T.; Ishibashi, S.; Yamada, N. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J. Biol. Chem., 1999, 274(50), 35832-35839.
[] [PMID: 10585467]
Shimano, H. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog. Lipid Res., 2001, 40(6), 439-452.
[] [PMID: 11591434]
Zhao, X.; Xiaoli, ; Zong, H.; Abdulla, A.; Yang, E.S.; Wang, Q.; Ji, J.Y.; Pessin, J.E.; Das, B.C.; Yang, F. Inhibition of SREBP transcriptional activity by a boron-containing compound improves lipid homeostasis in diet-induced obesity. Diabetes, 2014, 63(7), 2464-2473.
[] [PMID: 24608444]
Kim, D.D.; Krishnarajah, J.; Lillioja, S.; de Looze, F.; Marjason, J.; Proietto, J.; Shakib, S.; Stuckey, B.G.A.; Vath, J.E.; Hughes, T.E. Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial. Diabetes Obes. Metab., 2015, 17(6), 566-572.
[] [PMID: 25732625]
Hughes, T.E.; Kim, D.D.; Marjason, J.; Proietto, J.; Whitehead, J.P.; Vath, J.E. Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women. Obesity (Silver Spring), 2013, 21(9), 1782-1788.
[] [PMID: 23512440]
Rupnick, M.A.; Panigrahy, D.; Zhang, C.Y.; Dallabrida, S.M.; Lowell, B.B.; Langer, R.; Folkman, M.J. Adipose tissue mass can be regulated through the vasculature. Proc. Natl. Acad. Sci. USA, 2002, 99(16), 10730-10735.
[] [PMID: 12149466]
Lee, S.; Yang, W.K.; Song, J.H.; Ra, Y.M.; Jeong, J.H.; Choe, W.; Kang, I.; Kim, S.S.; Ha, J. Anti-obesity effects of 3-hydroxychromone derivative, a novel small-molecule inhibitor of glycogen synthase kinase-3. Biochem. Pharmacol., 2013, 85(7), 965-976.
[] [PMID: 23337568]
Shi, L.; Wang, J.; Wang, Y.; Feng, Y. MDG-1, an Ophiopogon polysaccharide, alleviates hyperlipidemia in mice based on metabolic profile of bile acids. Carbohydr. Polym., 2016, 150, 74-81.
[] [PMID: 27312615]
Edwards, P.A.; Kast, H.R.; Anisfeld, A.M. BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis. J. Lipid Res., 2002, 43(1), 2-12.
[PMID: 11792716]
Calkin, A.C.; Tontonoz, P. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nat. Rev. Mol. Cell Biol., 2012, 13(4), 213-224.
[] [PMID: 22414897]
Souza, G.A.; Ebaid, G.X.; Seiva, F.R.; Rocha, K.H.; Galhardi, C.M.; Mani, F.; Novelli, E.L. N-acetylcysteine an allium plant compound improves high-sucrose diet-induced obesity and related effects. Evid. Based Complement. Alternat. Med., 2011, 2011, 643269
[] [PMID: 19001480]
Mela, D.J.; Rogers, P.J. Energy intake and expenditure: basic concepts and issues; Springer: US, 1998.
Bonet, M.L.; Oliver, P.; Palou, A. Pharmacological and nutritional agents promoting browning of white adipose tissue. Biochim. Biophys. Acta, 2013, 1831(5), 969-985.
[] [PMID: 23246573]
Ricquier, D.; Bouillaud, F. Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance. J. Physiol., 2000, 529(Pt 1), 3-10.
[] [PMID: 11080246]
Brand, M.D.; Esteves, T.C. Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab., 2005, 2(2), 85-93.
[] [PMID: 16098826]
Maeda, H.; Hosokawa, M.; Sashima, T.; Murakami-Funayama, K.; Miyashita, K. Anti-obesity and anti-diabetic effects of fucoxanthin on diet-induced obesity conditions in a murine model. Mol. Med. Rep., 2009, 2(6), 897-902.
[] [PMID: 21475918]
Gammone, M.A.; D’Orazio, N. Anti-obesity activity of the marine carotenoid fucoxanthin. Mar. Drugs, 2015, 13(4), 2196-2214.
[] [PMID: 25871295]
Maeda, H. Nutraceutical effects of fucoxanthin for obesity and diabetes therapy: a review. J. Oleo Sci., 2015, 64(2), 125-132.
[] [PMID: 25748372]
Woo, M.N.; Jeon, S.M.; Shin, Y.C.; Lee, M.K.; Kang, M.A.; Choi, M.S. Anti-obese property of fucoxanthin is partly mediated by altering lipid-regulating enzymes and uncoupling proteins of visceral adipose tissue in mice. Mol. Nutr. Food Res., 2009, 53(12), 1603-1611.
[] [PMID: 19842104]
Fu, Y.Y.; Zhang, M.; Turner, N.; Zhang, L.N.; Dong, T.C.; Gu, M.; Leslie, S.J.; Li, J.Y.; Nan, F.J.; Li, J. A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake. Diabetologia, 2013, 56(10), 2297-2307.
[] [PMID: 23912111]
Zhang, Z.; Zhang, H.; Li, B.; Meng, X.; Wang, J.; Zhang, Y.; Yao, S.; Ma, Q.; Jin, L.; Yang, J.; Wang, W.; Ning, G. Berberine activates thermogenesis in white and brown adipose tissue. Nat. Commun., 2014, 5(5), 5493.
[] [PMID: 25423280]
Ma, X.; Xu, L.; Alberobello, A.T.; Gavrilova, O.; Bagattin, A.; Skarulis, M.; Liu, J.; Finkel, T.; Mueller, E. Celastrol protects against obesity and metabolic dysfunction through activation of a HSF1-PGC1α transcriptional axis. Cell Metab., 2015, 22(4), 695-708.
[] [PMID: 26344102]
Wankhade, U.D.; Shen, M.; Yadav, H.; Thakali, K.M. Novel browning agents, mechanisms, and therapeutic potentials of brown adipose tissue. BioMed Res. Int., 2016, 2016, 2365609
[] [PMID: 28105413]
Silvester, A.J.; Aseer, K.R.; Yun, J.W. Dietary polyphenols and their roles in fat browning. J. Nutr. Biochem., 2019, 64, 1-12.
[] [PMID: 30414469]
Joo, J.I.; Kim, D.H.; Choi, J-W.; Yun, J.W. Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet. J. Proteome Res., 2010, 9(6), 2977-2987.
[] [PMID: 20359164]
Choi, J.H.; Kim, S.W.; Yu, R.; Yun, J.W. Monoterpene phenolic compound thymol promotes browning of 3T3-L1 adipocytes. Eur. J. Nutr., 2017, 56(7), 2329-2341.
[] [PMID: 27431894]
Parray, H.A.; Lone, J.; Park, J.P.; Choi, J.W.; Yun, J.W. Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes. Nutrition, 2018, 50, 82-90.
[] [PMID: 29547798]
Gregoire, F.M.; Smas, C.M.; Sul, H.S. Understanding adipocyte differentiation. Physiol. Rev., 1998, 78(3), 783-809.
[] [PMID: 9674695]
Gregoire, F.M. Adipocyte differentiation: from fibroblast to endocrine cell. Exp. Biol. Med. (Maywood), 2001, 226(11), 997-1002.
White, U.A.; Stephens, J.M. Transcriptional factors that promote formation of white adipose tissue. Mol. Cell. Endocrinol., 2010, 318(1-2), 10-14.
[] [PMID: 19733624]
Cristancho, A.G.; Lazar, M.A. Forming functional fat: a growing understanding of adipocyte differentiation. Nat. Rev. Mol. Cell Biol., 2011, 12(11), 722-734.
[] [PMID: 21952300]
Hwang, J.T.; Lee, M.S.; Kim, H.J.; Sung, M.J.; Kim, H.Y.; Kim, M.S.; Kwon, D.Y. Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways. Phytother. Res., 2009, 23(2), 262-266.
[] [PMID: 18844326]
Hwang, J-T.; Kim, S-H.; Lee, M-S.; Kim, S.H.; Yang, H-J.; Kim, M-J.; Kim, H-S.; Ha, J.; Kim, M.S.; Kwon, D.Y. Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte. Biochem. Biophys. Res. Commun., 2007, 364(4), 1002-1008.
[] [PMID: 17971295]
Siraj, F.M.; SathishKumar, N.; Kim, Y.J.; Kim, S.Y.; Yang, D.C. Ginsenoside F2 possesses anti-obesity activity via binding with PPARγ and inhibiting adipocyte differentiation in the 3T3-L1 cell line. J. Enzyme Inhib. Med. Chem., 2015, 30(1), 9-14.
[] [PMID: 24666293]
Gu, W.; Kim, K.A.; Kim, D.H. Ginsenoside Rh1 ameliorates high fat diet-induced obesity in mice by inhibiting adipocyte differentiation. Biol. Pharm. Bull., 2013, 36(1), 102-107.
[] [PMID: 23302642]
Park, D.; Yoon, M.; Compound, K. Compound K, a novel ginsenoside metabolite, inhibits adipocyte differentiation in 3T3-L1 cells: involvement of angiogenesis and MMPs. Biochem. Biophys. Res. Commun., 2012, 422(2), 263-267.
[] [PMID: 22575448]
Liu, Q.; Zhang, X.L.; Tao, R.Y.; Niu, Y.J.; Chen, X.G.; Tian, J.Y.; Ye, F. Rhein, an inhibitor of adipocyte differentiation and adipogenesis. J. Asian Nat. Prod. Res., 2011, 13(8), 714-723.
[] [PMID: 21751839]
Seo, J.B.; Choe, S.S.; Jeong, H.W.; Park, S.W.; Shin, H.J.; Choi, S.M.; Park, J.Y.; Choi, E.W.; Kim, J.B.; Seen, D.S.; Jeong, J.Y.; Lee, T.G. Anti-obesity effects of Lysimachia foenum-graecum characterized by decreased adipogenesis and regulated lipid metabolism. Exp. Mol. Med., 2011, 43(4), 205-215.
[] [PMID: 21389766]
Seo, J.B.; Park, S.W.; Choe, S.S.; Jeong, H.W.; Park, J.Y.; Choi, E.W.; Seen, D.S.; Jeong, J.Y.; Lee, T.G. Foenumoside B from Lysimachia foenum-graecum inhibits adipocyte differentiation and obesity induced by high-fat diet. Biochem. Biophys. Res. Commun., 2012, 417(2), 800-806.
[] [PMID: 22197824]
Rahman, N.; Jeon, M.; Song, H.Y.; Kim, Y.S. Cryptotanshinone, a compound of Salvia miltiorrhiza inhibits pre-adipocytes differentiation by regulation of adipogenesis-related genes expression via STAT3 signaling. Phytomedicine, 2016, 23(1), 58-67.
[] [PMID: 26902408]
Altaf, Q.A.; Barnett, A.H.; Tahrani, A.A. Novel therapeutics for type 2 diabetes: insulin resistance. Diabetes Obes. Metab., 2015, 17(4), 319-334.
[] [PMID: 25308775]
de Luca, C.; Olefsky, J.M. Inflammation and insulin resistance. FEBS Lett., 2008, 582(1), 97-105.
[] [PMID: 18053812]
Kajimoto, Y.; Kaneto, H. Role of oxidative stress in pancreatic beta-cell dysfunction. Ann. N. Y. Acad. Sci., 2004, 1011(1), 168-176.
[] [PMID: 15126294]
Matsuzawa-Nagata, N.; Takamura, T.; Ando, H.; Nakamura, S.; Kurita, S.; Misu, H.; Ota, T.; Yokoyama, M.; Honda, M.; Miyamoto, K.; Kaneko, S. Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. Metabolism, 2008, 57(8), 1071-1077.
[] [PMID: 18640384]
Ravussin, E.; Smith, S.R. Increased fat intake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes mellitus. Ann. N. Y. Acad. Sci., 2002, 967(1), 363-378.
[] [PMID: 12079864]
Dandona, P.; Aljada, A.; Bandyopadhyay, A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol., 2004, 25(1), 4-7.
[] [PMID: 14698276]
Ye, J. Mechanisms of insulin resistance in obesity. Front. Med., 2013, 7(1), 14-24.
[] [PMID: 23471659]
Ding, L.; Li, J.; Song, B.; Xiao, X.; Zhang, B.; Qi, M.; Huang, W.; Yang, L.; Wang, Z. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway. Toxicol. Appl. Pharmacol., 2016, 304, 99-109.
[] [PMID: 27208389]
Shao, W.; Yu, Z.; Chiang, Y.; Yang, Y.; Chai, T.; Foltz, W.; Lu, H.; Fantus, I.G.; Jin, T. Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS One, 2012, 7(1), e28784
[] [PMID: 22253696]
Zheng, Z.G.; Zhou, Y.P.; Zhang, X.; Thu, P.M.; Xie, Z.S.; Lu, C.; Pang, T.; Xue, B.; Xu, D.Q.; Chen, Y.; Chen, X.W.; Li, H.J.; Xu, X. Anhydroicaritin improves diet-induced obesity and hyperlipidemia and alleviates insulin resistance by suppressing SREBPs activation. Biochem. Pharmacol., 2016, 122, 42-61.
[] [PMID: 27816546]
Fjære, E.; Aune, U.L.; Røen, K.; Keenan, A.H.; Ma, T.; Borkowski, K.; Kristensen, D.M.; Novotny, G.W.; Mandrup-Poulsen, T.; Hudson, B.D.; Milligan, G.; Xi, Y.; Newman, J.W.; Haj, F.G.; Liaset, B.; Kristiansen, K.; Madsen, L. Indomethacin treatment prevents high fat diet-induced obesity and insulin resistance but not glucose intolerance in C57BL/6J mice. J. Biol. Chem., 2014, 289(23), 16032-16045.
[] [PMID: 24742673]
Ozcan, L.; Xu, X.; Deng, S.X.; Ghorpade, D.S.; Thomas, T.; Cremers, S.; Hubbard, B.; Serrano-Wu, M.H.; Gaestel, M.; Landry, D.W.; Tabas, I. Treatment of obese insulin-resistant mice with an allosteric MAPKAPK2/3 inhibitor lowers blood glucose and improves insulin sensitivity. Diabetes, 2015, 64(10), 3396-3405.
[] [PMID: 26068544]
Xu, N.; Zhang, L.; Dong, J.; Zhang, X.; Chen, Y.G.; Bao, B.; Liu, J. Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice. Mol. Nutr. Food Res., 2014, 58(6), 1258-1268.
[] [PMID: 24668788]
Zhang, L.; Han, Y.J.; Zhang, X.; Wang, X.; Bao, B.; Qu, W.; Liu, J. Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages. Diabetologia, 2016, 59(10), 2219-2228.
[] [PMID: 27377644]
Luft, V.C.; Schmidt, M.I.; Pankow, J.S.; Couper, D.; Ballantyne, C.M.; Young, J.H.; Duncan, B.B. Chronic inflammation role in the obesity-diabetes association: a case-cohort study. Diabetol. Metab. Syndr., 2013, 5(1), 31.
[] [PMID: 23806173]
Monteiro, R.; Azevedo, I. Chronic inflammation in obesity and the metabolic syndrome Chronic in-flammation in obesity and the metabolic syndrome. Mediators Inflamm., 2010, 2010, pii: 289645
[] [PMID: 20706689]
González-Chávez, A.; Elizondo-Argueta, S.; Gutiérrez-Reyes, G.; León-Pedroza, J.I. Pathophysiological implications between chronic inflammation and the development of diabetes and obesity. Cir. Cir., 2011, 79(2), 209-216.
[PMID: 21631985]
Dixon, R.A.; Ferreira, D. Genistein. Phytochemistry, 2002, 60(3), 205-211.
[] [PMID: 12031439]
Ibrahim, A.S.; El-Shishtawy, M.M.; Peña, A., Jr; Liou, G.I. Genistein attenuates retinal inflammation associated with diabetes by targeting of microglial activation. Mol. Vis., 2010, 16, 2033-2042.
[PMID: 21042558]
Saisho, Y. Metformin and inflammation: its potential beyond glucose-lowering effect. Endocr. Metab. Immune Disord. Drug Targets, 2015, 15(3), 196-205.
[] [PMID: 25772174]
Evia-Viscarra, M.L.; Rodea-Montero, E.R.; Apolinar-Jiménez, E.; Muñoz-Noriega, N.; García-Morales, L.M.; Leaños-Pérez, C.; Figueroa-Barrón, M.; Sánchez-Fierros, D.; Reyes-García, J.G. The effects of metformin on inflammatory mediators in obese adolescents with insulin resistance: controlled randomized clinical trial. J. Pediatr. Endocrinol. Metab., 2012, 25(1-2), 41-49.
[] [PMID: 22570949]
Fidan, E.; Onder Ersoz, H.; Yilmaz, M.; Yilmaz, H.; Kocak, M.; Karahan, C.; Erem, C. The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus. Acta Diabetol., 2011, 48(4), 297-302.
[] [PMID: 21424914]
Lu, A.; Wu, H. Structural mechanisms of inflammasome assembly. FEBS J., 2015, 282(3), 435-444.
[] [PMID: 25354325]
Honda, H.; Nagai, Y.; Matsunaga, T.; Okamoto, N.; Watanabe, Y.; Tsuneyama, K.; Hayashi, H.; Fujii, I.; Ikutani, M.; Hirai, Y.; Muraguchi, A.; Takatsu, K. Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation. J. Leukoc. Biol., 2014, 96(6), 1087-1100.
[] [PMID: 25210146]
Oh, D.Y.; Walenta, E.; Akiyama, T.E.; Lagakos, W.S.; Lackey, D.; Pessentheiner, A.R.; Sasik, R.; Hah, N.; Chi, T.J.; Cox, J.M.; Powels, M.A.; Di Salvo, J.; Sinz, C.; Watkins, S.M.; Armando, A.M.; Chung, H.; Evans, R.M.; Quehenberger, O.; McNelis, J.; Bogner-Strauss, J.G.; Olefsky, J.M.A.A. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat. Med., 2014, 20(8), 942-947.
[] [PMID: 24997608]
Lederberg, J. Infectious history. Science, 2000, 288(5464), 287-293.
[] [PMID: 10777411]
Lin, C.S.; Chang, C.J.; Lu, C.C.; Martel, J.; Ojcius, D.M.; Ko, Y.F.; Young, J.D.; Lai, H.C. Impact of the gut microbiota, prebiotics, and probiotics on human health and disease. Biomed. J., 2014, 37(5), 259-268.
[] [PMID: 25179725]
DiBaise, J.K.; Zhang, H.; Crowell, M.D.; Krajmalnik-Brown, R.; Decker, G.A.; Rittmann, B.E. Gut microbiota and its possible relationship with obesity. Mayo Clin. Proc., 2008, 83(4), 460-469.
[] [PMID: 18380992]
Shen, J.; Obin, M.S.; Zhao, L. The gut microbiota, obesity and insulin resistance. Mol. Aspects Med., 2013, 34(1), 39-58.
[] [PMID: 23159341]
Murphy, E.F.; Cotter, P.D.; Healy, S.; Marques, T.M.; O’Sullivan, O.; Fouhy, F.; Clarke, S.F.; O’Toole, P.W.; Quigley, E.M.; Stanton, C.; Ross, P.R.; O’Doherty, R.M.; Shanahan, F. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut, 2010, 59(12), 1635-1642.
[] [PMID: 20926643]
de La Serre, C.B.; Ellis, C.L.; Lee, J.; Hartman, A.L.; Rutledge, J.C.; Raybould, H.E. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am. J. Physiol. Gastrointest. Liver Physiol., 2010, 299(2), G440-G448.
[] [PMID: 20508158]
Verdam, F.J.; Fuentes, S.; de Jonge, C.; Zoetendal, E.G.; Erbil, R.; Greve, J.W.; Buurman, W.A.; de Vos, W.M.; Rensen, S.S. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring), 2013, 21(12), E607-E615.
[] [PMID: 23526699]
Kootte, R.S.; Vrieze, A.; Holleman, F.; Dallinga-Thie, G.M.; Zoetendal, E.G.; de Vos, W.M.; Groen, A.K.; Hoekstra, J.B.L.; Stroes, E.S.; Nieuwdorp, M. The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes. Metab., 2012, 14(2), 112-120.
[] [PMID: 21812894]
Hu, Y.; Davies, G.E. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice. Fitoterapia, 2010, 81(5), 358-366.
[] [PMID: 19861153]
Zhang, X.; Zhao, Y.; Zhang, M.; Pang, X.; Xu, J.; Kang, C.; Li, M.; Zhang, C.; Zhang, Z.; Zhang, Y.; Li, X.; Ning, G.; Zhao, L. 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
[] [PMID: 22880019]
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
[] [PMID: 21915347]
Masumoto, S.; Terao, A.; Yamamoto, Y.; Mukai, T.; Miura, T.; Shoji, T. Non-absorbable apple procyanidins prevent obesity associated with gut microbial and metabolomic changes. Sci. Rep., 2016, 6, 31208.
[] [PMID: 27506289]
Witkamp, R.F. Biologically active compounds in food products and their effects on obesity and diabetes. Comp. Nat. Prod., 2010, 3, 509-545.

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Year: 2020
Published on: 15 June, 2020
Page: [3577 - 3597]
Pages: 21
DOI: 10.2174/0929867326666190215114359
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