Abstract
Background: Metabolic disorders are a major cause of illness and death worldwide. Metabolism is the process by which the body makes energy from proteins, carbohydrates, and fats; chemically breaking these down in the digestive system towards sugars and acids which constitute the human body's fuel for immediate use, or to store in body tissues, such as the liver, muscles, and body fat.
Objective: The efficiency of treatments for multifactor diseases has not been proved. It is accepted that to manage multifactor diseases, simultaneous modulation of multiple targets is required leading to the development of new strategies for discovery and development of drugs against metabolic disorders.
Methods: In silico studies are increasingly being applied by researchers due to reductions in time and costs for new prototype synthesis; obtaining substances that present better therapeutic profiles.
Discussion: In the present work, in addition to discussing multi-target drug discovery and the contributions of in silico studies to rational bioactive planning against metabolic disorders such as diabetes and obesity, we review various in silico study contributions to the fight against human metabolic pathologies.
Conclusion: In this review, we have presented various studies involved in the treatment of metabolic disorders; attempting to obtain hybrid molecules with pharmacological activity against various targets and expanding biological activity by using different mechanisms of action to treat a single pathology.
Keywords: Docking, multi-target drugs, polypharmacology, metabolic disorders, diabetes, obesity.
Graphical Abstract
[1]
Congenital anomalies fact sheet updated September 2016. Available at: http://www.who.int/mediacentre/factsheets/fs370/en/
(Accessed
December 1, 2017).
[2]
Metabolic disorders: MedlinePlus. www.nlm.nih.gov. Retrieved 27
July 2015. Available at: www.nlm.nih.govhttps://medlineplus.gov/metabolicdisorders.html (Accessed December 1, 2017).
[3]
Inherited metabolic disorders overview: overview, clinical features
and differential diagnosis, epidemiology and statistics. https://emedicine.medscape.com/article/1183253-overview (Accessed December 1, 2017).
[4]
Csermely, P.; Agoston, V.; Pongor, S. The efficiency of multi-target drugs: The network approach might help drug design. Trends Pharmacol. Sci., 2005, 26(4), 178-182.
[6]
Rogawski, M.A. Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability. Amino Acids, 2000, 19(1), 133-149.
[7]
Longo, M.G.; Vairo, F.; Souza, C.F.; Giugliani, R.; Vedolin, L.M. Brain imaging and genetic risk in the pediatric population, part 1: inherited metabolic diseases. Neuroimaging Clin. N. Am., 2015, 25(1), 31-51.
[8]
Kalache, A.; Keller, I. Ageing in developing countries.Increasing longevity: medical, social and political implications; Tallis, R., Ed.; Royal College of Physicians of London: London, 1998, pp. 69-80.
[9]
Site of the Brazilian institute of geography and statistics. http://www.ibge.gov.br/home/estatistica/populacao/ censo2000/populacao/censo2000_populacao.pdf
(Accessed December
1, 2017).
[10]
Chen, S.Y.; Chen, Y.; Li, Y.P.; Chen, S.H.; Tan, J.H.; Ou, T.M.; Gu, L.Q.; Huang, Z.S. Design, synthesis, and biological evaluation of curcumin analogues as multifunctional agents for the treatment of Alzheimer’s disease. Bioorg. Med. Chem., 2011, 19(18), 5596-5604.
[11]
Ray, B.; Lahiri, D.K. Neuroinflammation in Alzheimer’s disease: Different molecular targets and potential therapeutic agents including curcumin. Curr. Opin. Pharmacol., 2009, 9(4), 434-444.
[12]
Viegas, F.P.D.; Simões, M.C.R.; Rocha, M.D.; Castelli, M.R.; Moreira, M.S. Viegas, Junior, C. Doença de Alzheimer: caracterização, evolução e implicações do processo neuroinflamatório. Rev. Virtual Quim., 2011, 3, 286-306.
[13]
Palsson, B. Methods for identifying drug targets based on genomic sequence data. US Patent 20020012939, 2001.
[14]
Cornish-Bowden, A.; Cárdenas, M.L. Metabolic analysis in drug design. C. R. Biol., 2003, 326(5), 509-515.
[15]
Youdim, M.B.H.; Buccafusco, J.J. Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol. Sci., 2005, 26(1), 27-35.
[16]
Bolognesi, M.L.; Matera, R.; Minarini, A.; Rosini, M.; Melchiorre, C. Alzheimer’s disease: New approaches to drug discovery. Curr. Opin. Chem. Biol., 2009, 13(3), 303-308.
[17]
Piau, A.; Nourhashémi, F.; Hein, C.; Caillaud, C.; Vellas, B. Progress in the development of new drugs in Alzheimer’s disease. J. Nutr. Health Aging, 2011, 15(1), 45-57.
[18]
Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem., 2008, 51(3), 347-372.
[19]
Costantino, L.; Barlocco, D. Challenges in the design of multitarget drugs against multifactorial pathologies: A new life for medicinal chemistry? Future Med. Chem., 2013, 5(1), 5-7.
[20]
Korcsmáros, T.; Szalay, M.S.; Böde, C.; Kovács, I.A.; Csermely, P. How to design multi-target drugs. Expert Opin. Drug Discov., 2007, 2(6), 799-808.
[21]
Hughes, R.E.; Nikolic, K.; Ramsay, R.R. One for all hitting multiple alzheimer’s disease targets with one drug. Front. Neurosci., 2016, 10, 177.
[22]
Ekins, S.; Mestres, J.; Testa, B. In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br. J. Pharmacol., 2007, 152(1), 9-20.
[23]
Scotti, L.; Filho, F.J.; de Moura, R.O.; Ribeiro, F.F.; Ishiki, H.; da Silva, M.S.; Filho, J.M.; Scotti, M.T. Multi-target drugs for neglected diseases. Curr. Pharm. Des., 2016, 22(21), 3135-3163.
[24]
Scotti, L.; Ishiki, H.; Mendonça Júnior, F.J.; Da Silva, M.S.; Scotti, M.T. In-silico analyses of natural products on leishmania enzyme targets. Mini Rev. Med. Chem., 2015, 15(3), 253-269.
[25]
Scotti, L.; Mendonca, F.J., Junior; Ishiki, H.M.; Ribeiro, F.F.; Singla, R.K.; Barbosa Filho, J.M.; Da Silva, M.S.; Scotti, M.T. Docking studies for multi-target drugs. Curr. Drug Targets, 2017, 18(5), 592-604.
[26]
Mendonça Júnior, F.J.; Scotti, L.; Ishiki, H.; Botelho, S.P.S.; Da Silva, M.S.; Scotti, M.T. Benzo- and thienobenzo- diazepines: multi-target drugs for CNS disorders. Mini Rev. Med. Chem., 2015, 15(8), 630-647.
[27]
Scotti, L.; Bezerra Mendonça, F.J., Junior; Magalhaes Moreira, D.R.; da Silva, M.S.; Pitta, I.R.; Scotti, M.T. SAR, QSAR and docking of anticancer flavonoids and variants: a review. Curr. Top. Med. Chem., 2012, 12(24), 2785-2809.
[28]
Hopkins, A.L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[29]
Wishart, D.S.; Knox, C.; Guo, A.C.; Shrivastava, S.; Hassanali, M.; Stothard, P.; Chang, Z.; Woolsey, J. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res., 2006, 34(Database issue), D668-D672.
[30]
Wunberg, T.; Hendrix, M.; Hillisch, A.; Lobell, M.; Meier, H.; Schmeck, C.; Wild, H.; Hinzen, B. Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits. Drug Discov. Today, 2006, 11(3-4), 175-180.
[31]
Ma, X.H.; Shi, Z.; Tan, C.; Jiang, Y.; Go, M.L.; Low, B.C.; Chen, Y.Z. In-silico approaches to multi-target drug discovery: Computer aided multi-target drug design, multi-target virtual screening. Pharm. Res., 2010, 27(5), 739-749.
[32]
Knight, J.; Nigam, Y.; Andrade, M. Diabetes management 1: Disease types, symptoms and diagnosis. Nurs. Times, 2017, 113(4), 40-44.
[33]
Bluestone, J.A.; Herold, K.; Eisenbarth, G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature, 2010, 464(7293), 1293-1300.
[35]
Stumvoll, M.; Goldstein, B.J.; van Haeften, T.W. Type 2 diabetes: principles of pathogenesis and therapy. Lancet, 2005, 365(9467), 1333-1346.
[36]
Gu, J.; Zhang, H.; Chen, L.; Xu, S.; Yuan, G.; Xu, X. Drug-target network and polypharmacology studies of a Traditional Chinese Medicine for type II diabetes mellitus. Comput. Biol. Chem., 2011, 35(5), 293-297.
[37]
Sengupta, U.; Ukil, S.; Dimitrova, N.; Agrawal, S. Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications. PLoS One, 2009, 4(12), e8100.
[38]
Smith, S.C., Jr Multiple risk factors for cardiovascular disease and diabetes mellitus. Am. J. Med., 2007, 120(3)(Suppl. 1), S3-S11.
[39]
Mazzone, T.; Chait, A.; Plutzky, J. Cardiovascular disease risk in type 2 diabetes mellitus: Insights from mechanistic studies. Lancet, 2008, 371(9626), 1800-1809.
[40]
Tian, S.; Li, Y.; Li, D.; Xu, X.; Wang, J.; Zhang, Q.; Hou, T. Modeling compound-target interaction network of traditional Chinese medicines for type II diabetes mellitus: insight for polypharmacology and drug design. J. Chem. Inf. Model., 2013, 53(7), 1787-1803.
[41]
Kahn, S.E.; Cooper, M.E.; Del Prato, S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet, 2014, 383(9922), 1068-1083.
[42]
Wishart, D.S.; Knox, C.; Guo, A.C.; Cheng, D.; Shrivastava, S.; Tzur, D.; Gautam, B.; Hassanali, M. DrugBank: A knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res., 2008, 36(Database issue), D901-D906.
[43]
Kanehisa, M.; Goto, S.; Furumichi, M.; Tanabe, M.; Hirakawa, M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res., 2010, 38(Database issue), D355-D360.
[44]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[45]
Tian, S.; Li, Y.; Wang, J.; Xu, X.; Xu, L.; Wang, X.; Chen, L.; Hou, T. Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines. J. Cheminform., 2013, 5(1), 5.
[46]
Zhu, F.; Shi, Z.; Qin, C.; Tao, L.; Liu, X.; Xu, F.; Zhang, L.; Song, Y.; Liu, X.; Zhang, J.; Han, B.; Zhang, P.; Chen, Y. Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res., 2012, 40(Database issue), D1128-D1136.
[47]
Moller, D.E. New drug targets for type 2 diabetes and the metabolic syndrome. Nature, 2001, 414(6865), 821-827.
[48]
Qiao, X.; Hou, T.; Zhang, W.; Guo, S.; Xu, X. A 3D structure database of components from Chinese traditional medicinal herbs. J. Chem. Inf. Comput. Sci., 2002, 42(3), 481-489.
[49]
Shen, M.; Tian, S.; Li, Y.; Li, Q.; Xu, X.; Wang, J.; Hou, T. Drug-likeness analysis of traditional Chinese medicines: 1. property distributions of drug-like compounds, non-drug-like compounds and natural compounds from traditional Chinese medicines. J. Cheminform., 2012, 4(1), 31.
[50]
Tian, S.; Wang, J.; Li, Y.; Xu, X.; Hou, T. Drug-likeness analysis of traditional Chinese medicines: Prediction of drug-likeness using machine learning approaches. Mol. Pharm., 2012, 9(10), 2875-2886.
[51]
Chen, C.Y-C. TCM Database@Taiwan: The world’s largest traditional Chinese medicine database for drug screening in silico. PLoS One, 2011, 6(1), e15939.
[52]
Wang, F-R.; Yang, X-W.; Zhang, Y.; Liu, J-X.; Yang, X-B.; Liu, Y.; Shi, R-B. Three new isoflavone glycosides from Tongmai granules. J. Asian Nat. Prod. Res., 2011, 13(4), 319-329.
[53]
Liu, L.; Ma, Y.; Wang, R.L.; Xu, W.R.; Wang, S.Q.; Chou, K.C. Find novel dual-agonist drugs for treating type 2 diabetes by means of cheminformatics. Drug Des. Devel. Ther., 2013, 7, 279-288.
[54]
Markt, P.; Schuster, D.; Kirchmair, J.; Laggner, C.; Langer, T. Pharmacophore modeling and parallel screening for PPAR ligands. J. Comput. Aided Mol. Des., 2007, 21(10-11), 575-590.
[55]
Xu, H.E.; Lambert, M.H.; Montana, V.G.; Plunket, K.D.; Moore, L.B.; Collins, J.L.; Oplinger, J.A.; Kliewer, S.A.; Gampe, R.T., Jr; McKee, D.D.; Moore, J.T.; Willson, T.M. Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. USA, 2001, 98(24), 13919-13924.
[56]
Waites, C.R.; Dominick, M.A.; Sanderson, T.P.; Schilling, B.E. Nonclinical safety evaluation of muraglitazar, a novel PPARalpha/gamma agonist. Toxicol. Sci., 2007, 100(1), 248-258.
[57]
Heppner, T.J.; Bonev, A.D.; Eckman, D.M.; Gomez, M.F.; Petkov, G.V.; Nelson, M.T. Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries. Pharmacology, 2005, 73(1), 15-22.
[58]
Pavankuamr, V.V.; Vinu, C.A.; Mullangi, R.; Srinivas, N.R. Preclinical pharmacokinetics and interspecies scaling of ragaglitazar, a novel biliary excreted PPAR dual activator. Eur. J. Drug Metab. Pharmacokinet., 2007, 32(1), 29-37.
[59]
Skrumsager, B.K.; Nielsen, K.K.; Müller, M.; Pabst, G.; Drake, P.G.; Edsberg, B. Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. J. Clin. Pharmacol., 2003, 43(11), 1244-1256.
[60]
Chakrabarti, R.; Vikramadithyan, R.K.; Misra, P.; Hiriyan, J.; Raichur, S.; Damarla, R.K.; Gershome, C.; Suresh, J.; Rajagopalan, R. Ragaglitazar: a novel PPAR alpha PPAR gamma agonist with potent lipid-lowering and insulin-sensitizing efficacy in animal models. Br. J. Pharmacol., 2003, 140(3), 527-537.
[61]
Wang, X.J.; Zhang, J.; Wang, S.Q.; Xu, W.R.; Cheng, X.C.; Wang, R.L. Identification of novel multitargeted PPARα/γ/δ pan agonists by core hopping of rosiglitazone. Drug Des. Devel. Ther., 2014, 8, 2255-2262.
[62]
Cronet, P.; Petersen, J.F.; Folmer, R.; Blomberg, N.; Sjöblom, K.; Karlsson, U.; Lindstedt, E.L.; Bamberg, K. Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family. Structure, 2001, 9(8), 699-706.
[63]
Nolte, R.T.; Wisely, G.B.; Westin, S.; Cobb, J.E.; Lambert, M.H.; Kurokawa, R.; Rosenfeld, M.G.; Willson, T.M.; Glass, C.K.; Milburn, M.V. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature, 1998, 395(6698), 137-143.
[64]
Oyama, T.; Toyota, K.; Waku, T.; Hirakawa, Y.; Nagasawa, N.; Kasuga, J.I.; Hashimoto, Y.; Miyachi, H.; Morikawa, K. Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures. Acta Crystallogr. D Biol. Crystallogr., 2009, 65(Pt 8), 786-795.
[65]
Navarrete-Vázquez, G.; Torres-Gómez, H.; Hidalgo-Figueroa, S.; Ramírez-Espinosa, J.J.; Estrada-Soto, S.; Medina-Franco, J.L.; León-Rivera, I.; Alarcón-Aguilar, F.J.; Almanza-Pérez, J.C. Synthesis, in vitro and in silico studies of a PPARγ and GLUT-4 modulator with hypoglycemic effect. Bioorg. Med. Chem. Lett., 2014, 24(18), 4575-4579.
[66]
Hidalgo-Figueroa, S.; Ramírez-Espinosa, J.J.; Estrada-Soto, S.; Almanza-Pérez, J.C.; Román-Ramos, R.; Alarcón-Aguilar, F.J.; Hernández-Rosado, J.V.; Moreno-Díaz, H.; Díaz-Coutiño, D.; Navarrete-Vázquez, G. Discovery of thiazolidine-2,4-dione/biphenylcarbonitrile hybrid as dual PPAR α/γ modulator with antidiabetic effect: in vitro, in silico and in vivo approaches. Chem. Biol. Drug Des., 2013, 81(4), 474-483.
[67]
Navarrete-Vázquez, G.; Paoli, P.; León-Rivera, I.; Villalobos-Molina, R.; Medina-Franco, J.L.; Ortiz-Andrade, R.; Estrada-Soto, S.; Camici, G.; Diaz-Coutiño, D.; Gallardo-Ortiz, I.; Martinez-Mayorga, K.; Moreno-Díaz, H. Synthesis, in vitro and computational studies of protein tyrosine phosphatase 1B inhibition of a small library of 2-arylsulfonylaminobenzothiazoles with antihyperglycemic activity. Bioorg. Med. Chem., 2009, 17(9), 3332-3341.
[68]
Torres-Piedra, M.; Ortiz-Andrade, R.; Villalobos-Molina, R.; Singh, N.; Medina-Franco, J.L.; Webster, S.P.; Binnie, M.; Navarrete-Vázquez, G.; Estrada-Soto, S. A comparative study of flavonoid analogues on streptozotocin-nicotinamide induced diabetic rats: quercetin as a potential antidiabetic agent acting via 11beta-hydroxysteroid dehydrogenase type 1 inhibition. Eur. J. Med. Chem., 2010, 45(6), 2606-2612.
[69]
Navarrete-Vázquez, G.; Alaniz-Palacios, A.; Hidalgo-Figueroa, S.; González-Acevedo, C.; Ávila-Villarreal, G.; Estrada-Soto, S.; Webster, S.P.; Medina-Franco, J.L.; López-Vallejo, F.; Guerrero-Álvarez, J.; Tlahuext, H. Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent. Bioorg. Med. Chem. Lett., 2013, 23(11), 3244-3247.
[70]
Abirami, N.; Natarajan, B. Isolation and Characterization of (4Z, 12Z)- Cyclopentadeca-4, 12-Dienone from Indian Medicinal Plant Grewia hirsuta and its Hyperglycemic Effect on 3 T3 and L6 Cell Lines. IJPPR, 2014, 6(2), 393-398.
[71]
Natarajan, A.; Sugumar, S.; Bitragunta, S.; Balasubramanyan, N. Molecular docking studies of (4Z, 12Z)-cyclopentadeca-4, 12-dienone from Grewia hirsuta with some targets related to type 2 diabetes. BMC Complement. Altern. Med., 2015, 15, 73.
[72]
Begum, A.; Begum, S.; Kvsrg, P.; Bharathi, K. In silico studies on functionalized azaglycine derivatives containing 2,4-thiazolidinedione scaffold on multiple targets. Int. J. Pharm. Pharm. Sci., 2017, 9(8), 209-215.
[73]
Kaladhar, D.S.V.G.K.; Yarla, N.S.; Anusha, N. Functional analysis and molecular docking studies of medicinal compounds for AChE and BChE in alzheimer’s disease and Type 2 diabetes mellitus. Aging Dis., 2013, 4(4), 186-200.
[74]
Zhang, Z.Y.; Wang, M.W. Obesity, a health burden of a global nature. Acta Pharmacol. Sin., 2012, 33(2), 145-147.
[75]
Jen, H.C.; Rickard, D.G.; Shew, S.B.; Maggard, M.A.; Slusser, W.M.; Dutson, E.P.; DeUgarte, D.A. Trends and outcomes of adolescent bariatric surgery in California, 2005-2007. Pediatrics, 2010, 126(4), e746-e753.
[76]
Obesity and overweight. WHO fact sheet N° 311. World Health Organization website; World Health Organization: Geneva, Switzerland, 2015.
[77]
Colon-Gonzalez, F.; Kim, G.W.; Lin, J.E.; Valentino, M.A.; Waldman, S.A. Obesity pharmacotherapy: what is next? Mol. Aspects Med., 2013, 34(1), 71-83.
[78]
CDC. Adult Obesity Facts. Centers for Disease Control and Prevention, 2014. Available at: https://www.cdc.gov/obesity/data/adult.html (Accessed December 1, 2017).
[79]
Heal, D.J.; Gosden, J.; Smith, S.L. What is the prognosis for new centrally-acting anti-obesity drugs? Neuropharmacology, 2012, 63(1), 132-146.
[80]
Prentice, A.M.; Jebb, S.A. Obesity in Britain: Gluttony or sloth? BMJ, 1995, 311(7002), 437-439.
[81]
Deedwania, P.C. Metabolic syndrome and vascular disease: Is nature or nurture leading the new epidemic of cardiovascular disease? Circulation, 2004, 109(1), 2-4.
[83]
Block, J.P.; Scribner, R.A.; DeSalvo, K.B. Fast food, race/ethnicity, and income: a geographic analysis. Am. J. Prev. Med., 2004, 27(3), 211-217.
[84]
Bowman, S.A.; Gortmaker, S.L.; Ebbeling, C.B.; Pereira, M.A.; Ludwig, D.S. Effects of fast-food consumption on energy intake and diet quality among children in a national household survey. Pediatrics, 2004, 113(1 Pt 1), 112-118.
[85]
Jensen, M.D.; Ryan, D.H.; Apovian, C.M.; Ard, J.D.; Comuzzie, A.G.; Donato, K.A.; Hu, F.B.; Hubbard, V.S.; Jakicic, J.M.; Kushner, R.F.; Loria, C.M.; Millen, B.E.; Nonas, C.A.; Pi-Sunyer, F.X.; Stevens, J.; Stevens, V.J.; Wadden, T.A.; Wolfe, B.M.; Yanovski, S.Z.; Jordan, H.S.; Kendall, K.A.; Lux, L.J.; Mentor-Marcel, R.; Morgan, L.C.; Trisolini, M.G.; Wnek, J.; Anderson, J.L.; Halperin, J.L.; Albert, N.M.; Bozkurt, B.; Brindis, R.G.; Curtis, L.H.; DeMets, D.; Hochman, J.S.; Kovacs, R.J.; Ohman, E.M.; Pressler, S.J.; Sellke, F.W.; Shen, W.K.; Smith, S.C., Jr; Tomaselli, G.F. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and The obesity society. Circulation, 2014, 129(25)(Suppl. 2), S102-S138.
[86]
Shrager, B.; Jibara, G.A.; Tabrizian, P.; Roayaie, S.; Ward, S.C. Resection of nonalcoholic steatohepatitis-associated hepatocellular carcinoma: a Western experience. Int. J. Surg. Oncol., 2012, 2012915128.
[87]
Calle, E.E.; Rodriguez, C.; Walker-Thurmond, K.; Thun, M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med., 2003, 348(17), 1625-1638.
[88]
Hall, J.E.; do Carmo, J.M.; da Silva, A.A.; Wang, Z.; Hall, M.E. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ. Res., 2015, 116(6), 991-1006.
[89]
Guh, D.P.; Zhang, W.; Bansback, N.; Amarsi, Z.; Birmingham, C.L.; Anis, A.H. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health, 2009, 9(1), 88.
[90]
Polonsky, K.S.; Klein, S. Gastric banding to treat obesity: Band-aid or breakthrough? Nat. Clin. Pract. Endocrinol. Metab., 2008, 4(8), 421.
[91]
Al-Muammar, M.N.; Khan, F. Obesity: The preventive role of the pomegranate (Punica granatum). Nutrition, 2012, 28(6), 595-604.
[92]
Meye, F.J.; Trezza, V.; Vanderschuren, L.J.; Ramakers, G.M.J.; Adan, R.A.H. Neutral antagonism at the cannabinoid 1 receptor: A safer treatment for obesity. Mol. Psychiatry, 2013, 18(12), 1294-1301.
[93]
James, W.P.T.; Caterson, I.D.; Coutinho, W.; Finer, N.; Van Gaal, L.F.; Maggioni, A.P.; Torp-Pedersen, C.; Sharma, A.M.; Shepherd, G.M.; Rode, R.A.; Renz, C.L. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N. Engl. J. Med., 2010, 363(10), 905-917.
[94]
Ioannides-Demos, L.L.; Piccenna, L.; McNeil, J.J. Pharmacotherapies for obesity: past, current, and future therapies. J. Obes., 2011, 2011179674.
[95]
Yanovski, S.Z.; Yanovski, J.A. Long-term drug treatment for obesity: A systematic and clinical review. JAMA, 2014, 311(1), 74-86.
[96]
Bellido, D. Sobrepeso y obesidad: el future del tratamiento de la obesidad. Libro Obesidad y Sobrepeso de La SEEDO, 2015, 3, 3-4.
[97]
Solas, M.; Milagro, F.I.; Martínez-Urbistondo, D.; Ramirez, M.J.; Martínez, J.A. Precision obesity treatments including pharmacogenetic and nutrigenetic approaches. Trends Pharmacol. Sci., 2016, 37(7), 575-593.
[98]
van Bloemendaal, L.; Ten Kulve, J.S.; la Fleur, S.E.; Ijzerman, R.G.; Diamant, M. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J. Endocrinol., 2014, 221(1), T1-T16.
[99]
Smith, S.M.; Meyer, M.; Trinkley, K.E. Phentermine/topiramate for the treatment of obesity. Ann. Pharmacother., 2013, 47(3), 340-349.
[100]
Ali, K.F.; Shukla, A.P.; Aronne, L.J. Bupropion-SR plus naltrexone-SR for the treatment of mild-to-moderate obesity. Expert Rev. Clin. Pharmacol., 2016, 9(1), 27-34.
[101]
Sweeting, A.N.; Tabet, E.; Caterson, I.D.; Markovic, T.P. Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. Diabetes Metab. Syndr. Obes., 2014, 7, 35-44.
[102]
Vorsanger, M.H.; Subramanyam, P.; Weintraub, H.S.; Lamm, S.H.; Underberg, J.A.; Gianos, E.; Goldberg, I.J.; Schwartzbard, A.Z. Cardiovascular effects of the new weight loss agents. J. Am. Coll. Cardiol., 2016, 68(8), 849-859.
[103]
Rodgers, R.J.; Tschöp, M.H.; Wilding, J.P. Anti-obesity drugs: Past, present and future. Dis. Model. Mech., 2012, 5(5), 621-626.
[104]
Gadde, K.M.; Allison, D.B. Combination pharmaceutical therapies for obesity. Expert Opin. Pharmacother., 2009, 10(6), 921-925.
[105]
Kakkar, A.K.; Dahiya, N. Drug treatment of obesity: current status and future prospects. Eur. J. Intern. Med., 2015, 26(2), 89-94.
[106]
Greenway, F.L.; Bray, G.A. Combination drugs for treating obesity. Curr. Diab. Rep., 2010, 10(2), 108-115.
[107]
Roth, J.D.; Trevaskis, J.L.; Turek, V.F.; Parkes, D.G. “Weighing in” on synergy: Preclinical research on neurohormonal anti-obesity combinations. Brain Res., 2010, 1350, 86-94.
[108]
Chatzigeorgiou, A.; Kandaraki, E.; Papavassiliou, A.G.; Koutsilieris, M. Peripheral targets in obesity treatment: A comprehensive update. Obes. Rev., 2014, 15(6), 487-503.
[109]
Morphy, R.; Kay, C.; Rankovic, Z. From magic bullets to designed multiple ligands. Drug Discov. Today, 2004, 9(15), 641-651.
[110]
Yu, H.; Jin, H.; Gong, W.; Wang, Z.; Liang, H. Pharmacological actions of multi-target-directed evodiamine. Molecules, 2013, 18(2), 1826-1843.
[111]
Martinez, J.A. Body-weight regulation: causes of obesity. Proc. Nutr. Soc., 2000, 59(3), 337-345.
[112]
Schoeller, D.A. The energy balance equation: Looking back and looking forward are two very different views. Nutr. Rev., 2009, 67(5), 249-254.
[113]
Gautron, L.; Elmquist, J.K.; Williams, K.W. Neural control of energy balance: Translating circuits to therapies. Cell, 2015, 161(1), 133-145.
[114]
Wilson, J.L.; Enriori, P.J. A talk between fat tissue, gut, pancreas and brain to control body weight. Mol. Cell. Endocrinol., 2015, 418(Pt 2), 108-119.
[115]
Fasshauer, M.; Blüher, M. Adipokines in health and disease. Trends Pharmacol. Sci., 2015, 36(7), 461-470.
[116]
Byrne, C.S.; Chambers, E.S.; Morrison, D.J.; Frost, G. The role of short chain fatty acids in appetite regulation and energy homeostasis. Int. J. Obes., 2015, 39(9), 1331-1338.
[117]
Greenway, F.L. Physiological adaptations to weight loss and factors favouring weight regain. Int. J. Obes., 2015, 39(8), 1188-1196.
[118]
Pucci, A.; Finer, N. New medications for treatment of obesity: Metabolic and cardiovascular effects. Can. J. Cardiol., 2015, 31(2), 142-152.
[119]
Martinez, J.A.; Milagro, F.I. Genetics of weight loss: A basis for personalized obesity management. Trends Food Sci. Technol., 2015, 42, 97-115.
[120]
Tentolouris, N.; Alexiadou, K.; Kokkinos, A.; Koukou, E.; Perrea, D.; Kyriaki, D.; Katsilambros, N. Meal-induced thermogenesis and macronutrient oxidation in lean and obese women after consumption of carbohydrate-rich and fat-rich meals. Nutrition, 2011, 27(3), 310-315.
[121]
Butsch, W.S. Obesity medications: what does the future look like? Curr. Opin. Endocrinol. Diabetes Obes., 2015, 22(5), 360-366.
[122]
Mordes, J.P.; Liu, C.; Xu, S. Medications for weight loss. Curr. Opin. Endocrinol. Diabetes Obes., 2015, 22(2), 91-97.
[123]
Guo, L.; Tabrizchi, R. Peroxisome proliferator-activated receptor gamma as a drug target in the pathogenesis of insulin resistance. Pharmacol. Ther., 2006, 111(1), 145-173.
[124]
Hsu, S.C.; Huang, C.J. Changes in liver PPARalpha mRNA expression in response to two levels of high-safflower-oil diets correlate with changes in adiposity and serum leptin in rats and mice. J. Nutr. Biochem., 2007, 18(2), 86-96.
[125]
Huang, T.H.; Peng, G.; Kota, B.P.; Li, G.Q.; Yamahara, J.; Roufogalis, B.D.; Li, Y. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids. Br. J. Pharmacol., 2005, 145(6), 767-774.
[126]
Li, Y.; Huang, T.H-W.; Yamahara, J. Salacia root, a unique Ayurvedic medicine, meets multiple targets in diabetes and obesity. Life Sci., 2008, 82(21-22), 1045-1049.
[127]
Jain, K.S.; Kathiravan, M.K.; Somani, R.S.; Shishoo, C.J. The biology and chemistry of hyperlipidemia. Bioorg. Med. Chem., 2007, 15(14), 4674-4699.
[128]
Pirat, C.; Farce, A.; Lebègue, N.; Renault, N.; Furman, C.; Millet, R.; Yous, S.; Speca, S.; Berthelot, P.; Desreumaux, P.; Chavatte, P. Targeting peroxisome proliferator-activated receptors (PPARs): Development of modulators. J. Med. Chem., 2012, 55(9), 4027-4061.
[129]
Okazaki, S.; Noguchi-Yachide, T.; Sakai, T.; Ishikawa, M.; Makishima, M.; Hashimoto, Y.; Yamaguchi, T. Discovery of N-(1-(3-(4-phenoxyphenyl)-1,2,4-oxadiazol-5-yl)ethyl)acetamides as novel acetyl-CoA carboxylase 2 (ACC2) inhibitors with peroxisome proliferator-activated receptor α/δ (PPARα/δ) dual agonistic activity. Bioorg. Med. Chem., 2016, 24(21), 5258-5269.
[130]
Masuzaki, H.; Paterson, J.; Shinyama, H.; Morton, N.M.; Mullins, J.J.; Seckl, J.R.; Flier, J.S. A transgenic model of visceral obesity and the metabolic syndrome. Science, 2001, 294(5549), 2166-2170.
[131]
Hammer, F.; Stewart, P.M. Cortisol metabolism in hypertension. Best Pract. Res. Clin. Endocrinol. Metab., 2006, 20(3), 337-353.
[132]
Ge, R.; Huang, Y.; Liang, G.; Li, X. 11beta-hydroxysteroid dehydrogenase type 1 inhibitors as promising therapeutic drugs for diabetes: status and development. Curr. Med. Chem., 2010, 17(5), 412-422.
[133]
Freund, T.F.; Katona, I.; Piomelli, D. Role of endogenous cannabinoids in synaptic signaling. Physiol. Rev., 2003, 83(3), 1017-1066.
[134]
Cuchel, M.; Rader, D.J. Microsomal transfer protein inhibition in humans. Curr. Opin. Lipidol., 2013, 24(3), 246-250.
[135]
Roevens, P.; Heeres, J.; Meerpoel, L.; Dupont, A.; Borghys, H.; Lammens, L.; Auwerx, L.; Staels, B.; De Chaffoy De Courcelles, D. Hypolipidemic effects of R103757, a potent stereoselective inhibitor of microsomal triglyceride transfer protein (MTP). Atherosclerosis, 1999, 144(Suppl. 1), 38.
[136]
Gruetzmann, R.; Beuck, M.; Mueller, U.; Nielsch, U. Bay 13-9952 (implitapide), an inhibitor of microsomal triglyceride transfer protein (MTP), blocks secretion of Apo-B lipoproteins. Atherosclerosis, 2000, 151, 91-92.
[137]
Tao, Y.X. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocr. Rev., 2010, 31(4), 506-543.
[138]
Wikberg, J.E.; Mutulis, F. Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction. Nat. Rev. Drug Discov., 2008, 7(4), 307-323.
[139]
Billes, S.K.; Sinnayah, P.; Cowley, M.A. Naltrexone/bupropion for obesity: An investigational combination pharmacotherapy for weight loss. Pharmacol. Res., 2014, 84, 1-11.
[140]
Kelly, M.J.; Loose, M.D.; Ronnekleiv, O.K. Opioids hyperpolarize beta-endorphin neurons via mu-receptor activation of a potassium conductance. Neuroendocrinology, 1990, 52(3), 268-275.
[141]
Cowley, M.A.; Smart, J.L.; Rubinstein, M.; Cerdán, M.G.; Diano, S.; Horvath, T.L.; Cone, R.D.; Low, M.J. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature, 2001, 411(6836), 480-484.
[142]
Ibrahim, N.; Bosch, M.A.; Smart, J.L.; Qiu, J.; Rubinstein, M.; Rønnekleiv, O.K.; Low, M.J.; Kelly, M.J. Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels. Endocrinology, 2003, 144(4), 1331-1340.
[143]
Elias, C.F.; Lee, C.; Kelly, J.; Aschkenasi, C.; Ahima, R.S.; Couceyro, P.R.; Kuhar, M.J.; Saper, C.B.; Elmquist, J.K. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron, 1998, 21(6), 1375-1385.
[144]
Kalra, S.P.; Dube, M.G.; Pu, S.; Xu, B.; Horvath, T.L.; Kalra, P.S. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr. Rev., 1999, 20(1), 68-100.
[145]
Kanatani, A.; Mashiko, S.; Murai, N.; Sugimoto, N.; Ito, J.; Fukuroda, T.; Fukami, T.; Morin, N.; MacNeil, D.J.; Van der Ploeg, L.H.; Saga, Y.; Nishimura, S.; Ihara, M. Role of the Y1 receptor in the regulation of neuropeptide Y-mediated feeding: comparison of wild-type, Y1 receptor-deficient, and Y5 receptor-deficient mice. Endocrinology, 2000, 141(3), 1011-1016.
[146]
Mashiko, S.; Moriya, R.; Ishihara, A.; Gomori, A.; Matsushita, H.; Egashira, S.; Iwaasa, H.; Takahashi, T.; Haga, Y.; Fukami, T.; Kanatani, A. Synergistic interaction between neuropeptide Y1 and Y5 receptor pathways in regulation of energy homeostasis. Eur. J. Pharmacol., 2009, 615(1-3), 113-117.
[147]
Carlini, V.P.; Varas, M.M.; Cragnolini, A.B.; Schiöth, H.B.; Scimonelli, T.N.; de Barioglio, S.R. Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem. Biophys. Res. Commun., 2004, 313(3), 635-641.
[148]
Date, Y.; Murakami, N.; Toshinai, K.; Matsukura, S.; Niijima, A.; Matsuo, H.; Kangawa, K.; Nakazato, M. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology, 2002, 123(4), 1120-1128.
[149]
Naleid, A.M.; Grace, M.K.; Cummings, D.E.; Levine, A.S. Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides, 2005, 26(11), 2274-2279.
[150]
Korbonits, M.; Grossman, A.B. Ghrelin: Update on a novel hormonal system. Eur. J. Endocrinol., 2004, 151(Suppl. 1), S67-S70.
[151]
Theander-Carrillo, C.; Wiedmer, P.; Cettour-Rose, P.; Nogueiras, R.; Perez-Tilve, D.; Pfluger, P.; Castaneda, T.R.; Muzzin, P.; Schürmann, A.; Szanto, I.; Tschöp, M.H.; Rohner-Jeanrenaud, F. Ghrelin action in the brain controls adipocyte metabolism. J. Clin. Invest., 2006, 116(7), 1983-1993.
[152]
Jerlhag, E.; Egecioglu, E.; Dickson, S.L.; Douhan, A.; Svensson, L.; Engel, J.A. Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens. Addict. Biol., 2007, 12(1), 6-16.
[153]
Skibicka, K.P.; Hansson, C.; Egecioglu, E.; Dickson, S.L. Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression. Addict. Biol., 2012, 17(1), 95-107.
[154]
Cummings, D.E.; Purnell, J.Q.; Frayo, R.S.; Schmidova, K.; Wisse, B.E.; Weigle, D.S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes, 2001, 50(8), 1714-1719.
[155]
Callahan, H.S.; Cummings, D.E.; Pepe, M.S.; Breen, P.A.; Matthys, C.C.; Weigle, D.S. Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans. J. Clin. Endocrinol. Metab., 2004, 89(3), 1319-1324.
[156]
Druce, M.R.; Wren, A.M.; Park, A.J.; Milton, J.E.; Patterson, M.; Frost, G.; Ghatei, M.A.; Small, C.; Bloom, S.R. Ghrelin increases food intake in obese as well as lean subjects. Int. J. Obes., 2005, 29(9), 1130-1136.
[157]
Adrian, T.E.; Ferri, G.L.; Bacarese-Hamilton, A.J.; Fuessl, H.S.; Polak, J.M.; Bloom, S.R. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology, 1985, 89(5), 1070-1077.
[158]
Onaga, T.; Zabielski, R.; Kato, S. Multiple regulation of peptide YY secretion in the digestive tract. Peptides, 2002, 23(2), 279-290.
[159]
le Roux, C.W.; Batterham, R.L.; Aylwin, S.J.; Patterson, M.; Borg, C.M.; Wynne, K.J.; Kent, A.; Vincent, R.P.; Gardiner, J.; Ghatei, M.A.; Bloom, S.R. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology, 2006, 147(1), 3-8.
[160]
Hort, Y.; Baker, E.; Sutherland, G.R.; Shine, J.; Herzog, H. Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1. Genomics, 1995, 26(1), 77-83.
[161]
Larhammar, D. Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regul. Pept., 1996, 65(3), 165-174.
[162]
Adrian, T.E.; Bloom, S.R.; Bryant, M.G.; Polak, J.M.; Heitz, P.H.; Barnes, A.J. Distribution and release of human pancreatic polypeptide. Gut, 1976, 17(12), 940-944.
[163]
Asakawa, A.; Inui, A.; Yuzuriha, H.; Ueno, N.; Katsuura, G.; Fujimiya, M.; Fujino, M.A.; Niijima, A.; Meguid, M.M.; Kasuga, M. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology, 2003, 124(5), 1325-1336.
[164]
Reinehr, T.; Enriori, P.J.; Harz, K.; Cowley, M.A.; Roth, C.L. Pancreatic polypeptide in obese children before and after weight loss. Int. J. Obes., 2006, 30(10), 1476-1481.
[165]
Myers, M.G., Jr Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog. Horm. Res., 2004, 59, 287-304.
[166]
Schwartz, M.W.; Seeley, R.J.; Woods, S.C.; Weigle, D.S.; Campfield, L.A.; Burn, P.; Baskin, D.G. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes, 1997, 46(12), 2119-2123.
[167]
Stephens, T.W.; Basinski, M.; Bristow, P.K.; Bue-Valleskey, J.M.; Burgett, S.G.; Craft, L.; Hale, J.; Hoffmann, J.; Hsiung, H.M.; Kriauciunas, A.; MacKellar, W.; Rosteck, P.R., Jr; Schoner, B.; Smith, D.; Tinsley, F.C.; Zhang, X-Y.; Heiman, M. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature, 1995, 377(6549), 530-532.
[168]
Halaas, J.L.; Gajiwala, K.S.; Maffei, M.; Cohen, S.L.; Chait, B.T.; Rabinowitz, D.; Lallone, R.L.; Burley, S.K.; Friedman, J.M. Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 1995, 269(5223), 543-546.
[169]
Campfield, L.A.; Smith, F.J.; Burn, P. The OB protein (leptin) pathway--A link between adipose tissue mass and central neural networks. Horm. Metab. Res., 1996, 28(12), 619-632.
[170]
Myers, M.G.; Cowley, M.A.; Münzberg, H. Mechanisms of leptin action and leptin resistance. Annu. Rev. Physiol., 2008, 70, 537-556.
[171]
Hommel, J.D.; Trinko, R.; Sears, R.M.; Georgescu, D.; Liu, Z.W.; Gao, X.B.; Thurmon, J.J.; Marinelli, M.; DiLeone, R.J. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron, 2006, 51(6), 801-810.
[173]
Tartaglia, L.A.; Dembski, M.; Weng, X.; Deng, N.; Culpepper, J.; Devos, R.; Richards, G.J.; Campfield, L.A.; Clark, F.T.; Deeds, J.; Muir, C.; Sanker, S.; Moriarty, A.; Moore, K.J.; Smutko, J.S.; Mays, G.G.; Wool, E.A.; Monroe, C.A.; Tepper, R.I. Identification and expression cloning of a leptin receptor, OB-R. Cell, 1995, 83(7), 1263-1271.
[174]
Lee, G.H.; Proenca, R.; Montez, J.M.; Carroll, K.M.; Darvishzadeh, J.G.; Lee, J.I.; Friedman, J.M. Abnormal splicing of the leptin receptor in diabetic mice. Nature, 1996, 379(6566), 632-635.
[175]
Ozcan, L.; Ergin, A.S.; Lu, A.; Chung, J.; Sarkar, S.; Nie, D.; Myers, M.G., Jr; Ozcan, U. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab., 2009, 9(1), 35-51.
[176]
Cone, R.D. Anatomy and regulation of the central melanocortin system. Nat. Neurosci., 2005, 8(5), 571-578.
[177]
Woods, S.C.; Decke, E.; Vasselli, J.R. Metabolic hormones and regulation of body weight. Psychol. Rev., 1974, 81(1), 26-43.
[178]
Brange, J.; Langkjoer, L. Insulin structure and stability. Pharm. Biotechnol., 1993, 5, 315-350.
[179]
Menéndez, J.A.; Atrens, D.M. Insulin and the paraventricular hypothalamus: modulation of energy balance. Brain Res., 1991, 555(2), 193-201.
[180]
Palmiter, R.D. Is dopamine a physiologically relevant mediator of feeding behavior? Trends Neurosci., 2007, 30(8), 375-381.
[181]
Błajecka, K.; Borgström, A.; Arcaro, A. Phosphatidylinositol 3-kinase isoforms as novel drug targets. Curr. Drug Targets, 2011, 12(7), 1056-1081.
[182]
Di Gregorio, G.B.; Yao-Borengasser, A.; Rasouli, N.; Varma, V.; Lu, T.; Miles, L.M.; Ranganathan, G.; Peterson, C.A.; McGehee, R.E.; Kern, P.A. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes, 2005, 54(8), 2305-2313.
[183]
Engelman, J.A. Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat. Rev. Cancer, 2009, 9(8), 550-562.
[184]
Hattori, Y.; Suzuki, K.; Hattori, S.; Kasai, K. Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension, 2006, 47(6), 1183-1188.
[185]
Pittner, R.A.; Albrandt, K.; Beaumont, K.; Gaeta, L.S.; Koda, J.E.; Moore, C.X.; Rittenhouse, J.; Rink, T.J. Molecular physiology of amylin. J. Cell. Biochem., 1994, 55(Suppl.), 19-28.
[186]
Koda, J.E.; Fineman, M.S.; Kolterman, O.G.; Caro, J.F. 24 hour plasma amylin profiles are elevated in IGT subjects vs normal controls. Diabetes, 1995, 44(Suppl. 1), 238A.
[187]
Lutz, T.A.; Mollet, A.; Rushing, P.A.; Riediger, T.; Scharrer, E. The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats. Int. J. Obes. Relat. Metab. Disord., 2001, 25(7), 1005-1011.
[188]
Rushing, P.A.; Hagan, M.M.; Seeley, R.J.; Lutz, T.A.; D’Alessio, D.A.; Air, E.L.; Woods, S.C. Inhibition of central amylin signaling increases food intake and body adiposity in rats. Endocrinology, 2001, 142(11), 5035.
[189]
Qi, Y.; Takahashi, N.; Hileman, S.M.; Patel, H.R.; Berg, A.H.; Pajvani, U.B.; Scherer, P.E.; Ahima, R.S. Adiponectin acts in the brain to decrease body weight. Nat. Med., 2004, 10(5), 524-529.
[190]
Kadowaki, T.; Yamauchi, T. Adiponectin and adiponectin receptors. Endocr. Rev., 2005, 26(3), 439-451.
[192]
Näslund, E.; King, N.; Mansten, S.; Adner, N.; Holst, J.J.; Gutniak, M.; Hellström, P.M. Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects. Br. J. Nutr., 2004, 91(3), 439-446.
[193]
Turton, M.D.; O’Shea, D.; Gunn, I.; Beak, S.A.; Edwards, C.M.; Meeran, K.; Choi, S.J.; Taylor, G.M.; Heath, M.M.; Lambert, P.D.; Wilding, J.P.; Smith, D.M.; Ghatei, M.A.; Herbert, J.; Bloom, S.R. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature, 1996, 379(6560), 69-72.
[194]
Flint, A.; Raben, A.; Ersbøll, A.K.; Holst, J.J.; Astrup, A. The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int. J. Obes. Relat. Metab. Disord., 2001, 25(6), 781-792.
[195]
MacDonald, P.E.; De Marinis, Y.Z.; Ramracheya, R.; Salehi, A.; Ma, X.; Johnson, P.R.; Cox, R.; Eliasson, L.; Rorsman, P.A.K. ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans. PLoS Biol., 2007, 5(6), e143.
[196]
Cryer, P.E. Minireview: Glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology, 2012, 153(3), 1039-1048.
[197]
Sadry, S.A.; Drucker, D.J. Emerging combinatorial hormone therapies for the treatment of obesity and T2DM. Nat. Rev. Endocrinol., 2013, 9(7), 425-433.
[198]
Nair, K.S. Hyperglucagonemia increases resting metabolic rate in man during insulin deficiency. J. Clin. Endocrinol. Metab., 1987, 64(5), 896-901.
[199]
Berryman, D.E.; Glad, C.A.; List, E.O.; Johannsson, G. The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. Nat. Rev. Endocrinol., 2013, 9(6), 346-356.
[200]
Johannsson, G. Management of adult growth hormone deficiency. Endocrinol. Metab. Clin. North Am., 2007, 36(1), 203-220.
[201]
Schwartz, M.W.; Woods, S.C.; Porte, D., Jr; Seeley, R.J.; Baskin, D.G. Central nervous system control of food intake. Nature, 2000, 404(6778), 661-671.
[202]
Wang, G.J.; Volkow, N.D.; Fowler, J.S. The role of dopamine in motivation for food in humans: implications for obesity. Expert Opin. Ther. Targets, 2002, 6(5), 601-609.
[203]
Yin, H.H.; Knowlton, B.J.; Balleine, B.W. Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning. Eur. J. Neurosci., 2004, 19(1), 181-189.
[204]
Johnson, P.M.; Kenny, P.J. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat. Neurosci., 2010, 13(5), 635-641.
[205]
Wang, G-J.; Geliebter, A.; Volkow, N.D.; Telang, F.W.; Logan, J.; Jayne, M.C.; Galanti, K.; Selig, P.A.; Han, H.; Zhu, W.; Wong, C.T.; Fowler, J.S. Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity (Silver Spring), 2011, 19(8), 1601-1608.
[206]
Oltmans, G.A. Norepinephrine and dopamine levels in hypothalamic nuclei of the genetically obese mouse (ob/ob). Brain Res., 1983, 273(2), 369-373.
[207]
Leibowitz, S.F.; Roossin, P.; Rosenn, M. Chronic norepinephrine injection into the hypothalamic paraventricular nucleus produces hyperphagia and increased body weight in the rat. Pharmacol. Biochem. Behav., 1984, 21(5), 801-808.
[208]
Garfield, A.S.; Heisler, L.K. Pharmacological targeting of the serotonergic system for the treatment of obesity. J. Physiol., 2009, 587(1), 49-60.
[209]
Leibowitz, S.F.; Weiss, G.F.; Shor-Posner, G. Hypothalamic serotonin: pharmacological, biochemical, and behavioral analyses of its feeding-suppressive action. Clin. Neuropharmacol., 1988, 11(Suppl. 1), S51-S71.
[210]
Sargent, B.J.; Moore, N.A. New central targets for the treatment of obesity. Br. J. Clin. Pharmacol., 2009, 68(6), 852-860.
[211]
Minokoshi, Y.; Kim, Y.B.; Peroni, O.D.; Fryer, L.G.; Müller, C.; Carling, D.; Kahn, B.B. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature, 2002, 415(6869), 339-343.
[212]
Abu-Elheiga, L.; Matzuk, M.M.; Abo-Hashema, K.A.; Wakil, S.J. Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science, 2001, 291(5513), 2613-2616.
[213]
Kiens, B.; Alsted, T.J.; Jeppesen, J. Factors regulating fat oxidation in human skeletal muscle. Obes. Rev., 2011, 12(10), 852-858.
[214]
Dulloo, A.G. The search for compounds that stimulate thermogenesis in obesity management: from pharmaceuticals to functional food ingredients. Obes. Rev., 2011, 12(10), 866-883.
[215]
Alonso, A.; Sasin, J.; Bottini, N.; Friedberg, I.; Friedberg, I.; Osterman, A.; Godzik, A.; Hunter, T.; Dixon, J.; Mustelin, T. Protein tyrosine phosphatases in the human genome. Cell, 2004, 117(6), 699-711.
[216]
Elchebly, M.; Payette, P.; Michaliszyn, E.; Cromlish, W.; Collins, S.; Loy, A.L.; Normandin, D.; Cheng, A.; Himms-Hagen, J.; Chan, C.C.; Ramachandran, C.; Gresser, M.J.; Tremblay, M.L.; Kennedy, B.P. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science, 1999, 283(5407), 1544-1548.
[217]
Lee, S.; Wang, Q. Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B. Med. Res. Rev., 2007, 27(4), 553-573.
[218]
Gum, R.J.; Gaede, L.L.; Koterski, S.L.; Heindel, M.; Clampit, J.E.; Zinker, B.A.; Trevillyan, J.M.; Ulrich, R.G.; Jirousek, M.R.; Rondinone, C.M. Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice. Diabetes, 2003, 52(1), 21-28.
[219]
Nichols, A.J.; Mashal, R.D.; Balkan, B. Toward the discovery of small molecule PTP1B inhibitors for the treatment of metabolic diseases. Drug Dev. Res., 2006, 67(7), 559-566.
[220]
Sheng, H.; Sun, H. Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases. Nat. Prod. Rep., 2011, 28(3), 543-593.
[221]
Houten, S.M.; Watanabe, M.; Auwerx, J. Endocrine functions of bile acids. EMBO J., 2006, 25(7), 1419-1425.
[222]
Kawamata, Y.; Fujii, R.; Hosoya, M.; Harada, M.; Yoshida, H.; Miwa, M.; Fukusumi, S.; Habata, Y.; Itoh, T.; Shintani, Y.; Hinuma, S.; Fujisawa, Y.; Fujino, M.A. G protein-coupled receptor responsive to bile acids. J. Biol. Chem., 2003, 278(11), 9435-9440.
[223]
Watanabe, M.; Houten, S.M.; Mataki, C.; Christoffolete, M.A.; Kim, B.W.; Sato, H.; Messaddeq, N.; Harney, J.W.; Ezaki, O.; Kodama, T.; Schoonjans, K.; Bianco, A.C.; Auwerx, J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature, 2006, 439(7075), 484-489.
[224]
Katsuma, S.; Hirasawa, A.; Tsujimoto, G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem. Biophys. Res. Commun., 2005, 329(1), 386-390.
[225]
Rudel, L.L.; Lee, R.G.; Parini, P. ACAT2 is a target for treatment of coronary heart disease associated with hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol., 2005, 25(6), 1112-1118.
[226]
Smith, S.J.; Cases, S.; Jensen, D.R.; Chen, H.C.; Sande, E.; Tow, B.; Sanan, D.A.; Raber, J.; Eckel, R.H.; Farese, R.V. Jr Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat. Genet., 2000, 25(1), 87-90.
[227]
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.
[228]
Greenway, F.L.; Whitehouse, M.J.; Guttadauria, M.; Anderson, J.W.; Atkinson, R.L.; Fujioka, K.; Gadde, K.M.; Gupta, A.K.; O’Neil, P.; Schumacher, D.; Smith, D.; Dunayevich, E.; Tollefson, G.D.; Weber, E.; Cowley, M.A. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring), 2009, 17(1), 30-39.
[229]
Fleming, J.W.; McClendon, K.S.; Riche, D.M. New obesity agents: lorcaserin and phentermine/topiramate. Ann. Pharmacother., 2013, 47(7-8), 1007-1016.
[230]
Lee, S.; Sziklas, V.; Andermann, F.; Farnham, S.; Risse, G.; Gustafson, M.; Gates, J.; Penovich, P.; Al-Asmi, A.; Dubeau, F.; Jones-Gotman, M. The effects of adjunctive topiramate on cognitive function in patients with epilepsy. Epilepsia, 2003, 44(3), 339-347.
[231]
Bray, G.A.; Hollander, P.; Klein, S.; Kushner, R.; Levy, B.; Fitchet, M.; Perry, B.H. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes. Res., 2003, 11(6), 722-733.
[232]
Shukla, A.P.; Buniak, W.I.; Aronne, L.J. Treatment of obesity in 2015. J. Cardiopulm. Rehabil. Prev., 2015, 35(2), 81-92.
[233]
Herranz-López, M.; Olivares-Vicente, M.; Encinar, J.A.; Barrajón-Catalán, E.; Segura-Carretero, A.; Joven, J.; Micol, V. Multi-targeted molecular effects of Hibiscus sabdariffa polyphenols: An opportunity for a global approach to obesity. Nutrients, 2017, 9(8), e907.
[234]
Jiménez-Sánchez, C.; Olivares-Vicente, M.; Rodríguez-Pérez, C.; Herranz-López, M.; Lozano-Sánchez, J.; Segura-Carretero, A.; Fernández-Gutiérrez, A.; Encinar, J.A.; Micol, V. AMPK modulatory activity of olive-tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach. PLoS One, 2017, 12(3), e0173074.
[235]
Sasaki, T.; Mita, M.; Ikari, N.; Kuboyama, A.; Hashimoto, S.; Kaneko, T.; Ishiguro, M.; Shimizu, M.; Inoue, J.; Sato, R. Identification of key amino acid residues in the hTGR5-nomilin interaction and construction of its binding model. PLoS One, 2017, 12(6), e0179226.
[236]
Glisan, S.L.; Grove, K.A.; Yennawar, N.H.; Lambert, J.D. Inhibition of pancreatic lipase by black tea theaflavins: Comparative enzymology and in silico modeling studies. Food Chem., 2017, 216, 296-300.
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