Antiobesity Drug Discovery Research: In vitro Models for Shortening the
Drug Discovery Pipeline

Radheshyam; Priyanka      Gauniya; Mona      Semalty; Ajay      Semalty
Abstract

Obesity is a growing global health problem, leading to various chronic diseases. Despite standard treatment options, the prevalence of obesity continues to rise, emphasizing the need for new drugs. in vitro methods of drug discovery research provide a time and cost-saving platform to identify new antiobesity drugs. The review covers various aspects of obesity and drug discovery research using in vitro models. Besides discussing causes, diagnosis, prevention, and treatment, the review focuses on the advantages and limitations of in vitro studies and exhaustively covers models based on enzymes and cell lines from different animal species and humans. In contrast to conventional in vivo animal investigations, in vitro preclinical tests using enzyme- and cell line-based assays provide several advantages in development of antiobesity drugs. These methods are quick, affordable, and provide high-throughput screening. They can also yield insightful information about drug-target interactions, modes of action, and toxicity profiles. By shedding light on the factors that lead to obesity, in vitro tests can also present a chance for personalized therapy. Technology will continue to evolve, leading to the creation of more precise and trustworthy in vitro assays, which will become more and more crucial in the search for novel antiobesity medications.
Graphical Abstract

[1]
WHO Consultation on Obesity (‎1999: Geneva, Switzerland)‎ & World Health Organization. (‎2000)‎. Obesity: preventing and managing the global epidemic: report of a WHO consultation. 1999. Available from: https://apps.who.int/iris/handle/10665/42330 (Accessed April 04, 2023).

[2]
Popkin BM. The world is fat: the fads, trends, policies, and products that are fattening the human race. New York: Avery-Trade/Penguin Group 2009.

[3]
Singla P, Bardoloi A, Parkash AA. Metabolic effects of obesity: A review. World J Diabetes  2010; 1(3): 76-88.
 [http://dx.doi.org/10.4239/wjd.v1.i3.76] [PMID: 21537431]

[4]
Derdemezis CS, Voulgari PV, Drosos AA, Kiortsis DN. Obesity, adipose tissue and rheumatoid arthritis: Coincidence or more complex relationship? Clin Exp Rheumatol  2011; 29(4): 712-27.
 [PMID: 21640051]

[5]
Withrow D, Alter DA. The economic burden of obesity worldwide: A systematic review of the direct costs of obesity. Obes Rev  2011; 12(2): 131-41.
 [http://dx.doi.org/10.1111/j.1467-789X.2009.00712.x] [PMID: 20122135]

[6]
Popkin BM, Kim S, Rusev ER, Du S, Zizza C. Measuring the full economic costs of diet, physical activity and obesity-related chronic diseases. Obes Rev  2006; 7(3): 271-93.
 [http://dx.doi.org/10.1111/j.1467-789X.2006.00230.x] [PMID: 16866975]

[7]
World Health Organization.. 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (Accessed April 04 2023).

[8]
World obesity day atlases..  Available from: https://data.worldobesity.org/publications/?cat=19 (Accessed April 04 2023).

[9]
World obesity day..  Available from: https://www.worldobesityday.org/resources/entry/worldobesity-atlas-2023 (Accessed April 04 2023).

[10]
World obesity day atlases obesity atlas.  Available from: https://data.worldobesity.org/publications/?cat=19 (Accessed April 04 2023).

[11]
Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell  2014; 156(1-2): 20-44.
 [http://dx.doi.org/10.1016/j.cell.2013.12.012] [PMID: 24439368]

[12]
Chouchani ET, Kazak L, Spiegelman BM. New advances in adaptive thermogenesis: UCP1 and beyond. Cell Metab  2019; 29(1): 27-37.
 [http://dx.doi.org/10.1016/j.cmet.2018.11.002] [PMID: 30503034]

[13]
Fan R, You M, Toney AM, et al. Red raspberry polyphenols attenuate high-fat diet-driven activation of NLRP3 inflammasome and its paracrine suppression of adipogenesis via histone modifications. Mol Nutr Food Res  2020; 64(15): 1900995.
 [http://dx.doi.org/10.1002/mnfr.201900995] [PMID: 31786828]

[14]
Wang S, Liang X, Yang Q, et al. Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) α1 in mice fed high-fat diet. Mol Nutr Food Res  2017; 61(4): 1600746.
 [http://dx.doi.org/10.1002/mnfr.201600746] [PMID: 27873458]

[15]
Zhang Z, Zhang H, Li B, et al. Berberine activates thermogenesis in white and brown adipose tissue. Nat Commun  2014; 5(1): 5493.
 [http://dx.doi.org/10.1038/ncomms6493] [PMID: 25423280]

[16]
Gurevich-Panigrahi T, Panigrahi S, Wiechec E, Los M. Obesity: Pathophysiology and clinical management. Curr Med Chem  2009; 16(4): 506-21.
 [http://dx.doi.org/10.2174/092986709787315568] [PMID: 19199918]

[17]
Ministry of Health Saudi Arabia.  Available from: https://www.moh.gov.sa/en/HealthAwareness/EducationalContent/Diseases/NonCommunicable/Pages/Obesity.aspx#:~:text=%E2%80%8B%E2%80%8BOverview%3A,and%20the%20calories%20you%20burn (Accessed April 06 2023).

[18]
Balaji M, Ganjayi MS, Hanuma Kumar GEN, Parim BN, Mopuri R, Dasari S. A review on possible therapeutic targets to contain obesity: The role of phytochemicals. Obes Res Clin Pract  2016; 10(4): 363-80.
 [http://dx.doi.org/10.1016/j.orcp.2015.12.004] [PMID: 26740473]

[19]
Semalty M, Adhikari L, Chauhan A, et al. Obesity and herbal drug research: Exploring the safer alternative and lead molecule. Curr Tradit Med  2017; 3(2): 74-92.
 [http://dx.doi.org/10.2174/2215083803666170309124540]

[20]
Daneschvar HL, Aronson MD, Smetana GW. FDA Approved anti-obesity drugs in the United States. Am J Med  2016; 129(8): 1-6.
 [http://dx.doi.org/10.1016/j.amjmed.2016.02.009]

[21]
Semalty M, Kumar R, Semalty A. Formulation and characterization of herbal formulation for antihyperlipidemic activity in diet induced obese mice. INDIAN DRUGS  2016; 53(7): 30-4.
 [http://dx.doi.org/10.53879/id.53.07.10479]

[22]
Madorran E, Stožer A, Bevc S, Maver U. in vitro toxicity model: Upgrades to bridge the gap between preclinical and clinical research. Bosn J Basic Med Sci  2019; 20(2): 157-68.
 [http://dx.doi.org/10.17305/bjbms.2019.4378] [PMID: 31621554]

[23]
Shi D, Mi G, Wang M, Webster TJ. in vitro and ex-vivo systems at the forefront of infection modeling and drug discovery. Biomaterials  2019; 198: 228-49.
 [http://dx.doi.org/10.1016/j.biomaterials.2018.10.030] [PMID: 30384974]

[24]
Haguet Q, Le Joubioux F, Chavanelle V, et al. Inhibitory potential of α-amylase, α-glucosidase, and pancreatic lipase by a formulation of five plant extracts: TOTUM-63. Int J Mol Sci  2023; 24(4): 3652.
 [http://dx.doi.org/10.3390/ijms24043652] [PMID: 36835060]

[25]
Thomas A, Allouche M, Basyn F, Brasseur R, Kerfelec B. Role of the lid hydrophobicity pattern in pancreatic lipase activity. J Biol Chem  2005; 280(48): 40074-83.
 [http://dx.doi.org/10.1074/jbc.M502123200] [PMID: 16179352]

[26]
Hou XD, Qin XY, Hou J, Tang H, Ge GB. The potential of natural sources for pancreatic lipase inhibitors: A solution of the obesity crisis? Expert Opin Drug Discov  2022; 17(12): 1295-8.
 [http://dx.doi.org/10.1080/17460441.2023.2156499] [PMID: 36508256]

[27]
Kim JH, Kim HJ, Park HW, Youn SH, Choi DY, Shin CS. Development of inhibitors against lipase and Î±-glucosidase from derivatives of monascus pigment. FEMS Microbiol Lett  2007; 276(1): 93-8.
 [http://dx.doi.org/10.1111/j.1574-6968.2007.00917.x] [PMID: 17937667]

[28]
Qin XY, Hou XD, Zhu GH, et al. Discovery and characterization of the naturally occurring inhibitors against human pancreatic lipase in Ampelopsis grossedentata. Front Nutr  2022; 9: 844195.
 [http://dx.doi.org/10.3389/fnut.2022.844195] [PMID: 35284458]

[29]
Olennikov DN, Chirikova NK, Kashchenko NI, Nikolaev VM, Kim SW, Vennos C. Bioactive phenolics of the genus Artemisia (Asteraceae): HPLC-DAD-ESI-TQ-MS/MS profile of the Siberian species and their inhibitory potential against α-amylase and α-glucosidase. Front Pharmacol  2018; 9: 756.
 [http://dx.doi.org/10.3389/fphar.2018.00756] [PMID: 30050443]

[30]
Uddin S, Brooks PR, Tran TD. Chemical characterization, α-glucosidase, α-amylase and lipase inhibitory properties of the Australian honey bee propolis. Foods  2022; 11(13): 1964.
 [http://dx.doi.org/10.3390/foods11131964] [PMID: 35804780]

[31]
Ramadan NS, El-Sayed NH, El-Toumy SA, et al. Anti-obesity evaluation of Averrhoa carambola l. leaves and assessment of its polyphenols as potential α-glucosidase inhibitors. Molecules  2022; 27(16): 5159.
 [http://dx.doi.org/10.3390/molecules27165159] [PMID: 36014395]

[32]
Mugaranja KP, Kulal A. Alpha glucosidase inhibition activity of phenolic fraction from Simarouba glauca: An in-vitro, in-silico and kinetic study. Heliyon  2020; 6(7): e04392.
 [http://dx.doi.org/10.1016/j.heliyon.2020.e04392] [PMID: 32671273]

[33]
Segeritz CP, Vallier L. Cell culture: Growing cells as model systems in vitro. In: Jalali M, Saldanha YL, Jalali M, Eds. Basic Science Methods for Clinical Researchers.  Academic Press 2017; pp. 151-72.
 [http://dx.doi.org/10.1016/B978-0-12-803077-6.00009-6]

[34]
Green H, Meuth M. An established pre-adipose cell line and its differentiation in culture. Cell  1974; 3(2): 127-33.
 [http://dx.doi.org/10.1016/0092-8674(74)90116-0] [PMID: 4426090]

[35]
Buacheen P, Karinchai J, Kammasit N, et al. Protective effect of Anoectochilus burmannicus extracts and its active compound, kinsenoside on adipocyte differentiation induced by benzyl butyl phthalate and bisphenol A. Sci Rep  2023; 13(1): 2939.
 [http://dx.doi.org/10.1038/s41598-023-30227-5] [PMID: 36806746]

[36]
Wada T, Miyazawa Y, Ikurumi M, et al. A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice. Nutr Metab  2023; 20(1): 10.
 [http://dx.doi.org/10.1186/s12986-023-00732-5] [PMID: 36774476]

[37]
Cai X, Wang S, Wang H, et al. Naringenin inhibits lipid accumulation by activating the AMPK pathway in vivo and in vitro. Food Sci Hum Wellness  2023; 12(4): 1174-83.
 [http://dx.doi.org/10.1016/j.fshw.2022.10.043]

[38]
Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev  1998; 78(3): 783-809.
 [http://dx.doi.org/10.1152/physrev.1998.78.3.783] [PMID: 9674695]

[39]
Vohra MS, Ahmad B, Serpell CJ, Parhar IS, Wong EH. Murine in vitro cellular models to better understand adipogenesis and its potential applications. Differentiation  2020; 115: 62-84.
 [http://dx.doi.org/10.1016/j.diff.2020.08.003] [PMID: 32891960]

[40]
Hernández-Mosqueira C, Velez-delValle C, Kuri-Harcuch W. Tissue alkaline phosphatase is involved in lipid metabolism and gene expression and secretion of adipokines in adipocytes. Biochim Biophys Acta, Gen Subj  2015; 1850(12): 2485-96.
 [http://dx.doi.org/10.1016/j.bbagen.2015.09.014] [PMID: 26391843]

[41]
Vazquez-Sandoval A, Velez-delValle C, Hernández-Mosqueira C, Marsch-Moreno M, Ayala-Sumuano JT, Kuri-Harcuch W. FAM129B is a cooperative protein that regulates adipogenesis. Biochem Biophys Res Commun  2023; 638: 66-75.
 [http://dx.doi.org/10.1016/j.bbrc.2022.11.042] [PMID: 36442234]

[42]
Héliès-Toussaint C, Fouché E, Naud N, et al. Opuntia cladode powders inhibit adipogenesis in 3 T3-F442A adipocytes and a high-fat-diet rat model by modifying metabolic parameters and favouring faecal fat excretion. BMC Complementary Medicine and Therapies  2020; 20(1): 33.
 [http://dx.doi.org/10.1186/s12906-020-2824-x] [PMID: 32024512]

[43]
Khalilpourfarshbafi M, Devi Murugan D, Abdul Sattar MZ, Sucedaram Y, Abdullah NA. Withaferin A inhibits adipogenesis in 3T3-F442A cell line, improves insulin sensitivity and promotes weight loss in high fat diet-induced obese mice. PLoS One  2019; 14(6): e0218792.
 [http://dx.doi.org/10.1371/journal.pone.0218792] [PMID: 31226166]

[44]
Wolins NE, Quaynor BK, Skinner JR, et al. OP9 mouse stromal cells rapidly differentiate into adipocytes: characterization of a useful new model of adipogenesis. J Lipid Res  2006; 47(2): 450-60.
 [http://dx.doi.org/10.1194/jlr.D500037-JLR200] [PMID: 16319419]

[45]
Lane JM, Doyle JR, Fortin JP, Kopin AS, Ordovás JM. Development of an OP9 derived cell line as a robust model to rapidly study adipocyte differentiation. PLoS One  2014; 9(11): e112123.
 [http://dx.doi.org/10.1371/journal.pone.0112123] [PMID: 25409310]

[46]
Nakano T, Kodama H, Honjo T. Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science  1994; 265(5175): 1098-101.
 [http://dx.doi.org/10.1126/science.8066449] [PMID: 8066449]

[47]
Yoshida Y, Takeda Y, Yamahara K, et al. Enhanced angiogenic properties of umbilical cord blood primed by OP9 stromal cells ameliorates neurological deficits in cerebral infarction mouse model. Sci Rep  2023; 13(1): 262.
 [http://dx.doi.org/10.1038/s41598-023-27424-7] [PMID: 36609640]

[48]
Zhu S, Zhang J, Wang W, Jiang X, Chen YQ. Blockage of NDUFB9-SCD1 pathway inhibits adipogenesis. J Physiol Biochem  2022; 78(2): 377-88.
 [http://dx.doi.org/10.1007/s13105-022-00876-7] [PMID: 35122619]

[49]
Andrews FV, Kim SM, Edwards L, Schlezinger JJ. Identifying adipogenic chemicals: Disparate effects in 3T3-L1, OP9 and primary mesenchymal multipotent cell models. Toxicol In Vitro 2020; 67: 104904.
 [http://dx.doi.org/10.1016/j.tiv.2020.104904] [PMID: 32473317]

[50]
Reznikoff CA, Brankow DW, Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res  1973; 33(12): 3231-8.
 [PMID: 4357355]

[51]
Dufau J, Shen JX, Couchet M, et al. in vitro and ex-vivo models of adipocytes. Am J Physiol Cell Physiol  2021; 320(5): C822-41.
 [http://dx.doi.org/10.1152/ajpcell.00519.2020] [PMID: 33439778]

[52]
Lee N, Kim I, Park S, et al. Creatine inhibits adipogenesis by downregulating insulin-induced activation of the phosphatidylinositol 3-kinase signaling pathway. Stem Cells Dev  2015; 24(8): 983-94.
 [http://dx.doi.org/10.1089/scd.2014.0130] [PMID: 25428599]

[53]
Beg M, Chauhan P, Varshney S, et al. A withanolide coagulin-L inhibits adipogenesis modulating Wnt/β-catenin pathway and cell cycle in mitotic clonal expansion. Phytomedicine  2014; 21(4): 406-14.
 [http://dx.doi.org/10.1016/j.phymed.2013.10.009] [PMID: 24252344]

[54]
Yun UJ, Song NJ, Yang DK, et al. miR-195a inhibits adipocyte differentiation by targeting the preadipogenic determinator Zfp423. J Cell Biochem  2015; 116(11): 2589-97.
 [http://dx.doi.org/10.1002/jcb.25204] [PMID: 25903991]

[55]
Hwang HJ, Hwang YJ, Kim YJ, Kim M, Hwang KA. Immature sword bean pods (Canavalia gladiata) inhibit adipogenesis in C3H10T1/2 cells and mice with high-fat diet–induced obesity. J Chin Med Assoc  2022; 85(1): 67-76.
 [http://dx.doi.org/10.1097/JCMA.0000000000000655] [PMID: 34966163]

[56]
Lee JS, Park JH, Kwon IK, Lim JY. Retinoic acid inhibits BMP4-induced C3H10T1/2 stem cell commitment to adipocyte via downregulating Smad/p38MAPK signaling. Biochem Biophys Res Commun  2011; 409(3): 550-5.
 [http://dx.doi.org/10.1016/j.bbrc.2011.05.042] [PMID: 21605549]

[57]
Shon M-S, Song J-H, Kim G-N. Anti-obese function of selenate, an essential micronutrient, by regulation of adipogenesis in C3H10T1/2 cells. Kor J Aesthet Cosmetol  2013; 11(3): 447-52.

[58]
Wang SJ, Lu WY, Liu KY. Adiponectin receptor agonist AdipoRon suppresses adipogenesis in C3H10T1/2 cells through the adenosine monophosphate-activated protein kinase signaling pathway. Mol Med Rep  2017; 16(5): 7163-9.
 [http://dx.doi.org/10.3892/mmr.2017.7450] [PMID: 28901521]

[59]
Garfield A S. Derivation of primary mouse embryonic fibroblast (PMEF) cultures. Methods Mol Biol  2010; 633: 19-27.
 [http://dx.doi.org/10.1007/978-1-59745-019-5_2]

[60]
Merkestein M, Laber S, McMurray F, et al. FTO influences adipogenesis by regulating mitotic clonal expansion. Nat Commun  2015; 6(1): 6792.
 [http://dx.doi.org/10.1038/ncomms7792] [PMID: 25881961]

[61]
Han J, Murthy R, Wood B, et al. ER stress signalling through eIF2α and CHOP, but not IRE1α, attenuates adipogenesis in mice. Diabetologia  2013; 56(4): 911-24.
 [http://dx.doi.org/10.1007/s00125-012-2809-5] [PMID: 23314846]

[62]
Wang Q, Jin F, Zhang J, Li Z, Yu D. Lipoxin A4 promotes adipogenic differentiation and browning of mouse embryonic fibroblasts. in vitro  Cell Dev Biol Anim  2021; 57(10): 953-61.
 [http://dx.doi.org/10.1007/s11626-021-00617-y] [PMID: 34811702]

[63]
Fei Z, Bera TK, Liu X, Xiang L, Pastan I. Ankrd26 gene disruption enhances adipogenesis of mouse embryonic fibroblasts. J Biol Chem  2011; 286(31): 27761-8.
 [http://dx.doi.org/10.1074/jbc.M111.248435] [PMID: 21669876]

[64]
Alexander DL, Ganem LG, Fernández-Salguero P, Gonzalez F, Jefcoate CR. Aryl-hydrocarbon receptor is an inhibitory regulator of lipid synthesis and of commitment to adipogenesis. J Cell Sci  1998; 111(22): 3311-22.
 [http://dx.doi.org/10.1242/jcs.111.22.3311] [PMID: 9788873]

[65]
Pang W, Wang Y, Wei N, et al. Sirt1 inhibits akt2-mediated porcine adipogenesis potentially by direct protein-protein interaction. PLoS One  2013; 8(8): e71576.
 [http://dx.doi.org/10.1371/journal.pone.0071576] [PMID: 23951196]

[66]
Ruiz-Ojeda F, Rupérez A, Gomez-Llorente C, Gil A, Aguilera C. Cell models and their application for studying adipogenic differentiation in relation to obesity: A Review. Int J Mol Sci  2016; 17(7): 1040.
 [http://dx.doi.org/10.3390/ijms17071040] [PMID: 27376273]

[67]
McGregor RA, Choi MS. microRNAs in the regulation of adipogenesis and obesity. Curr Mol Med  2011; 11(4): 304-16.
 [http://dx.doi.org/10.2174/156652411795677990] [PMID: 21506921]

[68]
Mai Y, Zhang Z, Yang H, et al. BMP and activin membrane-bound inhibitor (BAMBI) inhibits the adipogenesis of porcine preadipocytes through Wnt/β-catenin signaling pathway. Biochem Cell Biol  2014; 92(3): 172-82.
 [http://dx.doi.org/10.1139/bcb-2014-0011] [PMID: 24798646]

[69]
Pan S, Zheng Y, Zhao R, Yang X. miRNA-374 regulates dexamethasone-induced differentiation of primary cultures of porcine adipocytes. Horm Metab Res  2013; 45(7): 518-25.
 [http://dx.doi.org/10.1055/s-0033-1334896] [PMID: 23468252]

[70]
Riedel J, Badewien-Rentzsch B, Kohn B, Hoeke L, Einspanier R. Characterization of key genes of the renin–angiotensin system in mature feline adipocytes and during in vitro adipogenesis. J Anim Physiol Anim Nutr  2016; 100(6): 1139-48.
 [http://dx.doi.org/10.1111/jpn.12392] [PMID: 26452529]

[71]
Thatcher S, Yiannikouris F, Gupte M, Cassis L. The adipose renin–angiotensin system: Role in cardiovascular disease. Mol Cell Endocrinol  2009; 302(2): 111-7.
 [http://dx.doi.org/10.1016/j.mce.2009.01.019] [PMID: 19418627]

[72]
Esteve Ràfols M. Adipose tissue: Cell heterogeneity and functional diversity. Endocrinol Nutr  2014; 61(2): 100-12.
 [http://dx.doi.org/10.1016/j.endonu.2013.03.011] [PMID: 23834768]

[73]
Tsuji W, Rubin JP, Marra KG. Adipose-derived stem cells: Implications in tissue regeneration. World J Stem Cells  2014; 6(3): 312-21.
 [http://dx.doi.org/10.4252/wjsc.v6.i3.312] [PMID: 25126381]

[74]
Singh M, Thrimawithana T, Shukla R, Brennan CS, Adhikari B. Impact of phenolic extracts and potassium hydroxycitrate of Hibiscus sabdariffa on adipogenesis: A cellular study. Int J Food Sci Technol  2023; 58(3): 1204-18.
 [http://dx.doi.org/10.1111/ijfs.16269]

[75]
Xu Q, Mariman ECM, Blaak EE, Jocken JWE. Pharmacological agents targeting autophagy and their effects on lipolysis in human adipocytes. Mol Cell Endocrinol  2022; 544: 111555.
 [http://dx.doi.org/10.1016/j.mce.2022.111555] [PMID: 35031432]

[76]
Brännmark C, Paul A, Ribeiro D, et al. Increased adipogenesis of human adipose-derived stem cells on polycaprolactone fiber matrices. PLoS One  2014; 9(11): e113620.
 [http://dx.doi.org/10.1371/journal.pone.0113620] [PMID: 25419971]

[77]
Mladenova SG, Vasileva LV, Savova MS, et al. Anti-adipogenic effect of alchemilla monticola is mediated via PI3K/AKT signaling inhibition in human adipocytes. Front Pharmacol  2021; 12: 707507.
 [http://dx.doi.org/10.3389/fphar.2021.707507] [PMID: 34483915]

[78]
Lessard J, Laforest S, Pelletier M, Leboeuf M, Blackburn L, Tchernof A. Low abdominal subcutaneous preadipocyte adipogenesis is associated with visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state. Adipocyte  2014; 3(3): 197-205.
 [http://dx.doi.org/10.4161/adip.29385] [PMID: 25068086]

[79]
Bélanger C, Hould FS, Lebel S, Biron S, Brochu G, Tchernof A. Omental and subcutaneous adipose tissue steroid levels in obese men. Steroids  2006; 71(8): 674-82.
 [http://dx.doi.org/10.1016/j.steroids.2006.04.008] [PMID: 16762384]

[80]
Divoux A, Xie H, Li JL, et al. MicroRNA-196 regulates HOX gene expression in human gluteal adipose tissue. Obesity  2017; 25(8): 1375-83.
 [http://dx.doi.org/10.1002/oby.21896] [PMID: 28649807]

[81]
Hugo ER, Brandebourg TD, Comstock CES, Gersin KS, Sussman JJ, Ben-Jonathan N. LS14: A novel human adipocyte cell line that produces prolactin. Endocrinology  2006; 147(1): 306-13.
 [http://dx.doi.org/10.1210/en.2005-0989] [PMID: 16195405]

[82]
Lincoln CK, Gabridge MG. Cell culture contamination: Sources, consequences, prevention, and elimination. Methods Cell Biol  1998; 57: 49-65.
 [http://dx.doi.org/10.1016/S0091-679X(08)61571-X] [PMID: 9648099]

[83]
Nims RW, Price PJ. Best practices for detecting and mitigating the risk of cell culture contaminants. in vitro Cell Dev Biol Anim  2017; 53(10): 872-9.
 [http://dx.doi.org/10.1007/s11626-017-0203-9] [PMID: 29197027]

[84]
Geraghty RJ, Capes-Davis A, Davis JM, et al. Guidelines for the use of cell lines in biomedical research. Br J Cancer  2014; 111(6): 1021-46.
 [http://dx.doi.org/10.1038/bjc.2014.166] [PMID: 25117809]
Cite As
Current Drug Targets

Antiobesity Drug Discovery Research: In vitro Models for Shortening the Drug Discovery Pipeline

Abstract

Graphical Abstract
