Fruh SM. Obesity: risk factors, complications, and strategies for sustainable long-term weight management. J Am Assoc Nurse Pract. 2017;29(S1):S3–S14.
PubMed
PubMed Central
Google Scholar
Yang L, Colditz GA. Prevalence of overweight and obesity in the United States, 2007-2012. JAMA Intern Med. 2015;175(8):1412–3.
Article
PubMed
PubMed Central
Google Scholar
Martin KA, Mani MV, Mani A. New targets to treat obesity and the metabolic syndrome. Eur J Pharmacol. 2015;763(Pt A):64–74.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bornfeldt KE, Tabas I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab. 2011;14(5):575–85.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fedorenko A, Lishko PV, Kirichok Y. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell. 2012;151(2):400–13.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509–17.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293(2):E444–52.
Article
CAS
PubMed
Google Scholar
Betz MJ, Enerback S. Human brown adipose tissue: what we have learned so far. Diabetes. 2015;64(7):2352–60.
Article
CAS
PubMed
Google Scholar
Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19(10):1252–63.
Article
CAS
PubMed
Google Scholar
Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, Kahn PA, et al. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 2015;21(1):33–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, et al. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med. 2013;19(5):635–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Schweizer S, Liebisch G, Oeckl J, Hoering M, Seeliger C, Schiebel C, et al. The lipidome of primary murine white, brite, and brown adipocytes-Impact of beta-adrenergic stimulation. PLoS Biol. 2019;17(8):e3000412-e.
Article
Google Scholar
Moosavinasab S, Patterson J, Strouse R, Rastegar-Mojarad M, Regan K, Payne PR, Huang Y, et al. ‘RE:fine drugs’: an interactive dashboard to access drug repurposing opportunities. Database. 2016;2016(undefined):undefined.
Google Scholar
Liu H, Beck TN, Golemis EA, Serebriiskii IG. Integrating in silico resources to map a signaling network. Methods Mol Biol. 2014;1101(undefined):197–245.
Article
CAS
PubMed
Google Scholar
Andronis C, Sharma A, Virvilis V, Deftereos S, Persidis A. Literature mining, ontologies and information visualization for drug repurposing. Brief Bioinform. 2011;12(4):357–68.
Article
CAS
PubMed
Google Scholar
Watanabe M, Yamamoto T, Mori C, Okada N, Yamazaki N, Kajimoto K, et al. Cold-induced changes in gene expression in brown adipose tissue: implications for the activation of thermogenesis. Biol Pharm Bull. 2008;31(5):775–84.
Article
CAS
PubMed
Google Scholar
Keam SJ. Vibegron: first global approval. Drugs. 2018;78(17):1835–9.
Article
PubMed
Google Scholar
Al-Majed A, Bakheit AH, Abdel Aziz HA, Alharbi H, Al-Jenoobi FI. Pioglitazone. Profiles Drug Subst Excipients Relat Methodol. 2016;41:379–438.
Article
CAS
Google Scholar
Janani C, Ranjitha Kumari BD. PPAR gamma gene--a review. Diabetol Metab Syndr. 2015;9(1):46–50.
Article
CAS
Google Scholar
Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim SH. Rosiglitazone for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;(3):CD006063.
Lee JH, Woo YA, Hwang IC, Kim CY, Kim DD, Shim CK, et al. Quantification of CKD-501, lobeglitazone, in rat plasma using a liquid-chromatography/tandem mass spectrometry method and its applications to pharmacokinetic studies. J Pharm Biomed Anal. 2009;50(5):872–7.
Article
CAS
PubMed
Google Scholar
Taygerly JP, McGee LR, Rubenstein SM, Houze JB, Cushing TD, Li Y, et al. Discovery of INT131: a selective PPARgamma modulator that enhances insulin sensitivity. Bioorg Med Chem. 2013;21(4):979–92.
Article
CAS
PubMed
Google Scholar
Li PP, Shan S, Chen YT, Ning ZQ, Sun SJ, Liu Q, et al. The PPARalpha/gamma dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats. Br J Pharmacol. 2006;148(5):610–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Manoria PC, Chopra HK, Parashar SK, Dutta AL, Pinto B, Mullasari A, et al. The nuances of atherogenic dyslipidemia in diabetes: focus on triglycerides and current management strategies. Indian Heart J. 2013;65(6):683–90.
Article
CAS
PubMed
PubMed Central
Google Scholar
Poiley J, Steinberg AS, Choi YJ, Davis CS, Martin RL, McWherter CA, et al. A randomized, double-blind, active- and placebo-controlled efficacy and safety study of arhalofenate for reducing flare in patients with gout. Arthritis Rheum. 2016;68(8):2027–34.
Article
CAS
Google Scholar
Tong M, Deochand C, Didsbury J, de la Monte S. T3D-959: a multi-faceted disease remedial drug candidate for the treatment of Alzheimer’s disease. J Alzheimers Dis. 2016;51(1):123–38.
Article
CAS
PubMed
PubMed Central
Google Scholar
Boubia B, Poupardin O, Barth M, Binet J, Peralba P, Mounier L, et al. Design, synthesis, and evaluation of a novel series of indole sulfonamide peroxisome proliferator activated receptor (PPAR) alpha/gamma/delta triple activators: discovery of lanifibranor, a new antifibrotic clinical candidate. J Med Chem. 2018;61(6):2246–65.
Article
CAS
PubMed
Google Scholar
Navarrete C, Carrillo-Salinas F, Palomares B, Mecha M, Jimenez-Jimenez C, Mestre L, et al. Hypoxia mimetic activity of VCE-004.8, a cannabidiol quinone derivative: implications for multiple sclerosis therapy. J Neuroinflammation. 2018;15(1):64.
Article
PubMed
PubMed Central
CAS
Google Scholar
Heeren J, Scheja L. Brown adipose tissue and lipid metabolism. Curr Opin Lipidol. 2018;29(3):180–5.
Article
CAS
PubMed
Google Scholar
Bezafibrate Infarction Prevention (BIP) study. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation. 2000;102(1):21–7.
Wysocki J, Belowski D, Kalina M, Kochanski L, Okopien B, Kalina Z. Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome. Int J Clin Pharmacol Ther. 2004;42(4):212–7.
Article
CAS
PubMed
Google Scholar
Panchal SK, Wanyonyi S, Brown L. Selenium, vanadium, and chromium as micronutrients to improve metabolic syndrome. Curr Hypertens Rep. 2017;19(3):10.
Article
PubMed
CAS
Google Scholar
Bara-Jimenez W, Dimitrova T, Sherzai A, Favit A, Mouradian MM, Chase TN. Effect of monoamine reuptake inhibitor NS 2330 in advanced Parkinson’s disease. Mov Disord. 2004;19(10):1183–6.
Article
PubMed
Google Scholar
Astrup A, Meier DH, Mikkelsen BO, Villumsen JS, Larsen TM. Weight loss produced by tesofensine in patients with Parkinson’s or Alzheimer’s disease. Obesity. 2008;16(6):1363–9.
Article
CAS
PubMed
Google Scholar
Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360(15):1518–25.
Article
CAS
PubMed
Google Scholar
Labbe SM, Caron A, Bakan I, Laplante M, Carpentier AC, Lecomte R, et al. In vivo measurement of energy substrate contribution to cold-induced brown adipose tissue thermogenesis. FASEB J. 2015;29(5):2046–58.
Article
CAS
PubMed
Google Scholar
Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58(7):1526–31.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bargut TC, Aguila MB, Mandarim-de-Lacerda CA. Brown adipose tissue: updates in cellular and molecular biology. Tissue Cell. 2016;48(5):452–60.
Article
CAS
PubMed
Google Scholar
Townsend KL, Tseng YH. Brown fat fuel utilization and thermogenesis. Trends Endocrinol Metab. 2014;25(4):168–77.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hoeke G, Kooijman S, Boon MR, Rensen PC, Berbee JF. Role of brown fat in lipoprotein metabolism and atherosclerosis. Circ Res. 2016;118(1):173–82.
Article
CAS
PubMed
Google Scholar
Sidossis L, Kajimura S. Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J Clin Invest. 2015;125(2):478–86.
Article
PubMed
PubMed Central
Google Scholar
Fisher FM, Maratos-Flier E. Understanding the physiology of FGF21. Annu Rev Physiol. 2016;78:223–41.
Article
CAS
PubMed
Google Scholar
Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, et al. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014;20(12):1436–43.
Article
CAS
PubMed
PubMed Central
Google Scholar
Poekes L, Lanthier N, Leclercq IA. Brown adipose tissue: a potential target in the fight against obesity and the metabolic syndrome. Clin Sci. 2015;129(11):933–49.
Article
CAS
Google Scholar
Cawthorne MA, Sennitt MV, Arch JR, Smith SA. BRL 35135, a potent and selective atypical beta-adrenoceptor agonist. Am J Clin Nutr. 1992;55(1 Suppl):252s–7s.
Article
CAS
PubMed
Google Scholar
Weyer C, Tataranni PA, Snitker S, Danforth E Jr, Ravussin E. Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans. Diabetes. 1998;47(10):1555–61.
Article
CAS
PubMed
Google Scholar
Larsen TM, Toubro S, van Baak MA, Gottesdiener KM, Larson P, Saris WH, et al. Effect of a 28-d treatment with L-796568, a novel beta (3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am J Clin Nutr. 2002;76(4):780–8.
Article
CAS
PubMed
Google Scholar
Redman LM, de Jonge L, Fang X, Gamlin B, Recker D, Greenway FL, et al. Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study. J Clin Endocrinol Metab. 2007;92(2):527–31.
Article
CAS
PubMed
Google Scholar
Arch JR. Challenges in beta (3)-adrenoceptor agonist drug development. Ther Adv Endocrinol Metab. 2011;2(2):59–64.
Article
CAS
PubMed
PubMed Central
Google Scholar
Malik M, van Gelderen EM, Lee JH, Kowalski DL, Yen M, Goldwater R, et al. Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, placebo-, and active-controlled thorough QT study. Clin Pharmacol Ther. 2012;92(6):696–706.
Article
CAS
PubMed
Google Scholar
Sacco E, Bientinesi R. Mirabegron: a review of recent data and its prospects in the management of overactive bladder. Ther Adv Urol. 2012;4(6):315–24.
Article
CAS
PubMed
PubMed Central
Google Scholar
Takasu T, Ukai M, Sato S, Matsui T, Nagase I, Maruyama T, et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther. 2007;321(2):642–7.
Article
CAS
PubMed
Google Scholar
Baskin AS, Linderman JD, Brychta RJ, McGehee S, Anflick-Chames E, Cero C, et al. Regulation of human adipose tissue activation, gallbladder size, and bile acid metabolism by a beta3-adrenergic receptor agonist. Diabetes. 2018;67(10):2113–25.
Article
CAS
PubMed
PubMed Central
Google Scholar
Finlin BS, Memetimin H, Confides AL, Kasza I, Zhu B, Vekaria HJ, et al. Human adipose beiging in response to cold and mirabegron. JCI Insight. 2018;3(15):e121510.
Article
PubMed Central
Google Scholar
Robidoux J, Cao W, Quan H, Daniel KW, Moukdar F, Bai X, et al. Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes. Mol Cell Biol. 2005;25(13):5466–79.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–8.
Article
PubMed
PubMed Central
CAS
Google Scholar
Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, et al. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature. 2009;460(7259):1154–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lin JC, Tarn WY, Hsieh WK. Emerging role for RNA binding motif protein 4 in the development of brown adipocytes. Biochim Biophys Acta. 2014;1843(4):769–79.
Article
CAS
PubMed
Google Scholar
Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med. 2004;10(4):355–61.
Article
CAS
PubMed
Google Scholar
Ohno H, Shinoda K, Spiegelman BM, Kajimura S. PPARgamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab. 2012;15(3):395–404.
Article
CAS
PubMed
PubMed Central
Google Scholar
Han L, Shen WJ, Bittner S, Kraemer FB, Azhar S. PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-alpha. Futur Cardiol. 2017;13(3):259–78.
Article
CAS
Google Scholar
Lehr T, Staab A, Tillmann C, Nielsen EO, Trommeshauser D, Schaefer HG, et al. Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach. Br J Pharmacol. 2008;153(1):164–74.
Article
CAS
PubMed
Google Scholar
Doggrell SA. Tesofensine--a novel potent weight loss medicine. Evaluation of: Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1906-13. Expert Opin Investig Drugs. 2009;18(7):1043–6.
Article
CAS
PubMed
Google Scholar
Sjodin A, Gasteyger C, Nielsen AL, Raben A, Mikkelsen JD, Jensen JK, et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes. 2010;34(11):1634–43.
Article
CAS
Google Scholar
Appel L, Bergstrom M, Buus Lassen J, Langstrom B. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. Eur Neuropsychopharmacol. 2014;24(2):251–61.
Article
CAS
PubMed
Google Scholar
Pubmed2ensembl. http://pubmed2ensembl.ls.manchester.ac.uk/. Accessed 1 Dec 2018.
Baran J, Gerner M, Haeussler M, Nenadic G, Bergman CM. pubmed2ensembl: a resource for mining the biological literature on genes. PLoS One. 2011;6(9):e24716.
Article
CAS
PubMed
PubMed Central
Google Scholar
GeneCodis. http://genecodis.cnb.csic.es/. Accessed 3 Dec 2018.
Tabas-Madrid D, Nogales-Cadenas R, Pascual-Montano A. GeneCodis3: a non-redundant and modular enrichment analysis tool for functional genomics. Nucleic Acids Res. 2012;40(Web Server issue):W478–83.
Article
CAS
PubMed
PubMed Central
Google Scholar
Carmona-Saez P, Chagoyen M, Tirado F, Carazo JM, Pascual-Montano A. GENECODIS: a web-based tool for finding significant concurrent annotations in gene lists. Genome Biol. 2007;8(1):R3.
Article
PubMed
PubMed Central
CAS
Google Scholar
STRING. http://string-db.org/. Accessed 5 Dec 2018.
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43(Database issue):D447–52.
Article
CAS
PubMed
Google Scholar
Su G, Morris JH, Demchak B, Bader GD. Biological network exploration with Cytoscape 3. Curr Protoc Bioinformatics. 2014;47:8.13.1–24.
Article
Google Scholar
The Human Protein Atlas. https://www.proteinatlas.org/. Accessed 1 Jan 2019.
Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.
Article
PubMed
CAS
Google Scholar
PharmaProjects. https://pharmaintelligence.informa.com/. Accessed 1 Jan 2019.
Jardim DL, Groves ES, Breitfeld PP, Kurzrock R. Factors associated with failure of oncology drugs in late-stage clinical development: a systematic review. Cancer Treat Rev. 2017;52:12–21.
Article
PubMed
Google Scholar