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ISSN (Online): 1873-4286

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Review Article

CRISPR/Cas9 Technology: A Novel Approach to Obesity Research

Author(s): Zahra Khademi, Zahra Mahmoudi, Vasily N. Sukhorukov, Tannaz Jamialahmadi and Amirhossein Sahebkar*

Volume 30, Issue 23, 2024

Published on: 30 May, 2024

Page: [1791 - 1803] Pages: 13

DOI: 10.2174/0113816128301465240517065848

Price: $65

Abstract

Gene editing technology, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has transformed medical research. As a newly developed genome editing technique, CRISPR technology has strongly assisted scientists in enriching their comprehension of the roles of individual genes and their influences on a vast spectrum of human malignancies. Despite considerable progress in elucidating obesity's molecular pathways, current anti-obesity medications fall short in effectiveness. A thorough understanding of the genetic foundations underlying various neurobiological pathways related to obesity, as well as the neuro-molecular mechanisms involved, is crucial for developing effective obesity treatments. Utilizing CRISPR-based technologies enables precise determination of the roles of genes that encode transcription factors or enzymes involved in processes, such as lipogenesis, lipolysis, glucose metabolism, and lipid storage within adipose tissue. This innovative approach allows for the targeted suppression or activation of genes regulating obesity, potentially leading to effective weight management strategies. In this review, we have provided a detailed overview of obesity's molecular genetics, the fundamentals of CRISPR/Cas9 technology, and how this technology contributes to the discovery and therapeutic targeting of new genes associated with obesity.

« Previous Next »
[1]
Haslam D, James W. Obesity. Lancet 2005; 366: 67483.
[2]
Hruby A, Hu FB. The epidemiology of obesity: A big picture. PharmacoEconomics 2015; 33(7): 673-89.
[http://dx.doi.org/10.1007/s40273-014-0243-x] [PMID: 25471927]
[3]
Hayden J, Strawn T, Zink B, Bostick BP. Targeted treatment of hfpef in a mouse model of western diet-induced obesity via viral gene therapy of antioxidant NRF2. J Am Coll Cardiol 2022; 79(9) (Suppl.): 322-2.
[http://dx.doi.org/10.1016/S0735-1097(22)01313-4]
[4]
Gadde KM, Martin CK, Berthoud HR, Heymsfield SB. Obesity. J Am Coll Cardiol 2018; 71(1): 69-84.
[http://dx.doi.org/10.1016/j.jacc.2017.11.011] [PMID: 29301630]
[5]
Jakab J, Miškić B, Mikšić Š, et al. Adipogenesis as a potential anti-obesity target: A review of pharmacological treatment and natural products. Diabetes Metab Syndr Obes 2021; 14: 67-83.
[http://dx.doi.org/10.2147/DMSO.S281186] [PMID: 33447066]
[6]
Pigeyre M, Yazdi FT, Kaur Y, Meyre D. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin Sci 2016; 130(12): 943-86.
[http://dx.doi.org/10.1042/CS20160136] [PMID: 27154742]
[7]
Romieu I, Dossus L, Barquera S, et al. Energy balance and obesity: What are the main drivers? Cancer Causes Control 2017; 28(3): 247-58.
[http://dx.doi.org/10.1007/s10552-017-0869-z] [PMID: 28210884]
[8]
Jayachandran M, Fei Z, Qu S. Genetic advancements in obesity management and CRISPR-Cas9-based gene editing system. Mol Cell Biochem 2022; 1-11.
[PMID: 35909208]
[9]
Kunej T, Skok DJ, Zorc M, et al. Obesity gene atlas in mammals. J Genomics 2013; 1: 45-55.
[http://dx.doi.org/10.7150/jgen.3996] [PMID: 25031655]
[10]
Li X, Qi L. Gene-environment interactions on body fat distribution. Int J Mol Sci 2019; 20(15): 3690.
[http://dx.doi.org/10.3390/ijms20153690] [PMID: 31357654]
[11]
Hill JO, Wyatt HR, Peters JC. Energy balance and obesity. Circulation 2012; 126(1): 126-32.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.087213] [PMID: 22753534]
[12]
Coughlin JW, Brantley PJ, Champagne CM, et al. The impact of continued intervention on weight: Five-year results from the weight loss maintenance trial. Obesity 2016; 24(5): 1046-53.
[http://dx.doi.org/10.1002/oby.21454] [PMID: 26991814]
[13]
Gadde KM, Apolzan JW, Berthoud HR. Pharmacotherapy for patients with obesity. Clin Chem 2018; 64(1): 118-29.
[http://dx.doi.org/10.1373/clinchem.2017.272815] [PMID: 29054924]
[14]
Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: A systematic and clinical review. JAMA 2014; 311(1): 74-86.
[http://dx.doi.org/10.1001/jama.2013.281361] [PMID: 24231879]
[15]
Franco-Tormo MJ, Salas-Crisostomo M, Rocha NB, Budde H, Machado S, Murillo-Rodríguez E. CRISPR/Cas9, the powerful new genome-editing tool for putative therapeutics in obesity. J Mol Neurosci 2018; 65(1): 10-6.
[http://dx.doi.org/10.1007/s12031-018-1076-4] [PMID: 29732484]
[16]
Loos RJF, Yeo GSH. The bigger picture of FTO-the first GWAS-identified obesity gene. Nat Rev Endocrinol 2014; 10(1): 51-61.
[http://dx.doi.org/10.1038/nrendo.2013.227] [PMID: 24247219]
[17]
Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822): 860-921.
[http://dx.doi.org/10.1038/35057062] [PMID: 11237011]
[18]
Wood AJ, Lo TW, Zeitler B, et al. Targeted genome editing across species using ZFNs and TALENs. Science 2011; 333(6040): 307-7.
[http://dx.doi.org/10.1126/science.1207773] [PMID: 21700836]
[19]
Mali P, Yang L, Esvelt KM, et al. RNA-guided human genome engineering via Cas9. Science 2013; 339(6121): 823-6.
[http://dx.doi.org/10.1126/science.1232033] [PMID: 23287722]
[20]
Urnov FD, Miller JC, Lee YL, et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 2005; 435(7042): 646-51.
[http://dx.doi.org/10.1038/nature03556] [PMID: 15806097]
[21]
Carroll D. Genome engineering with zinc-finger nucleases. Genetics 2011; 188(4): 773-82.
[http://dx.doi.org/10.1534/genetics.111.131433] [PMID: 21828278]
[22]
Ho B, Loh S, Chan W, Soh B. In vivo genome editing as a therapeutic approach. Int J Mol Sci 2018; 19(9): 2721.
[http://dx.doi.org/10.3390/ijms19092721] [PMID: 30213032]
[23]
Kim YG, Chandrasegaran S. Chimeric restriction endonuclease. Proc Natl Acad Sci USA 1994; 91(3): 883-7.
[http://dx.doi.org/10.1073/pnas.91.3.883] [PMID: 7905633]
[24]
Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet 2010; 11(9): 636-46.
[http://dx.doi.org/10.1038/nrg2842] [PMID: 20717154]
[25]
Miller JC, Tan S, Qiao G, et al. A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 2011; 29(2): 143-8.
[http://dx.doi.org/10.1038/nbt.1755] [PMID: 21179091]
[26]
Sung YH, Baek IJ, Kim DH, et al. Knockout mice created by TALEN-mediated gene targeting. Nat Biotechnol 2013; 31(1): 23-4.
[http://dx.doi.org/10.1038/nbt.2477] [PMID: 23302927]
[27]
Bogdanove AJ, Voytas DF. TAL effectors: Customizable proteins for DNA targeting. Science 2011; 333(6051): 1843-6.
[http://dx.doi.org/10.1126/science.1204094] [PMID: 21960622]
[28]
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337(6096): 816-21.
[http://dx.doi.org/10.1126/science.1225829] [PMID: 22745249]
[29]
Brouns SJJ, Jore MM, Lundgren M, et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 2008; 321(5891): 960-4.
[http://dx.doi.org/10.1126/science.1159689] [PMID: 18703739]
[30]
Fonfara I, Le Rhun A, Chylinski K, et al. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems. Nucleic Acids Res 2014; 42(4): 2577-90.
[http://dx.doi.org/10.1093/nar/gkt1074] [PMID: 24270795]
[31]
Yuan M, Webb E, Lemoine N, Wang Y. CRISPR-Cas9 as a powerful tool for efficient creation of oncolytic viruses. Viruses 2016; 8(3): 72.
[http://dx.doi.org/10.3390/v8030072] [PMID: 26959050]
[32]
Lander ES. The heroes of CRISPR. Cell 2016; 164(1-2): 18-28.
[http://dx.doi.org/10.1016/j.cell.2015.12.041] [PMID: 26771483]
[33]
Sorek R, Kunin V, Hugenholtz P. CRISPR - a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat Rev Microbiol 2008; 6(3): 181-6.
[http://dx.doi.org/10.1038/nrmicro1793] [PMID: 18157154]
[34]
Chandrasekaran M, Boopathi T, Paramasivan M. A status-quo review on CRISPR-Cas9 gene editing applications in tomato. Int J Biol Macromol 2021; 190: 120-9.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.08.169] [PMID: 34474054]
[35]
Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science 2010; 327(5962): 167-70.
[http://dx.doi.org/10.1126/science.1179555] [PMID: 20056882]
[36]
Rath D, Amlinger L, Rath A, Lundgren M. The CRISPR-Cas immune system: Biology, mechanisms and applications. Biochimie 2015; 117: 119-28.
[http://dx.doi.org/10.1016/j.biochi.2015.03.025] [PMID: 25868999]
[37]
Zhu S, Zhou Y, Wei W. Genome-wide CRISPR/Cas9 screening for high-throughput functional genomics in human cells. Innate Antiviral Immunity. Springer 2017; pp. 175-81.
[38]
Cong L, Ran FA, Cox D, et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339(6121): 819-23.
[http://dx.doi.org/10.1126/science.1231143] [PMID: 23287718]
[39]
Khademi Z, Ramezani M, Alibolandi M, et al. A novel dual-targeting delivery system for specific delivery of CRISPR/Cas9 using hyaluronic acid, chitosan and AS1411. Carbohydr Polym 2022; 292: 119691.
[http://dx.doi.org/10.1016/j.carbpol.2022.119691] [PMID: 35725215]
[40]
Kang X, Wang Y, Liu P, et al. Progresses, challenges, and prospects of CRISPR/Cas9 gene-editing in glioma studies. Cancers 2023; 15(2): 396.
[http://dx.doi.org/10.3390/cancers15020396] [PMID: 36672345]
[41]
Gaj T, Sirk SJ, Shui S, Liu J. Genome-editing technologies: Principles and applications. Cold Spring Harb Perspect Biol 2016; 8(12): a023754.
[http://dx.doi.org/10.1101/cshperspect.a023754] [PMID: 27908936]
[42]
Xu Z, Li Y, Li M, Xiang H, Yan A. Harnessing the type I CRISPR-CAS systems for genome editing in prokaryotes. Environ Microbiol 2021; 23(2): 542-58.
[http://dx.doi.org/10.1111/1462-2920.15116] [PMID: 32510745]
[43]
Pu Y, Wu W, Xiang H, Chen Y, Xu H. CRISPR/Cas9-based genome editing for multimodal synergistic cancer nanotherapy. Nano Today 2023; 48: 101734.
[http://dx.doi.org/10.1016/j.nantod.2022.101734]
[44]
Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol 2014; 32(3): 279-84.
[http://dx.doi.org/10.1038/nbt.2808] [PMID: 24463574]
[45]
Doudna JA, Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Science 2014; 346(6213): 1258096.
[http://dx.doi.org/10.1126/science.1258096] [PMID: 25430774]
[46]
Wang HX, Li M, Lee CM, et al. CRISPR/Cas9-based genome editing for disease modeling and therapy: Challenges and opportunities for nonviral delivery. Chem Rev 2017; 117(15): 9874-906.
[http://dx.doi.org/10.1021/acs.chemrev.6b00799] [PMID: 28640612]
[47]
Yin H, Kauffman KJ, Anderson DG. Delivery technologies for genome editing. Nat Rev Drug Discov 2017; 16(6): 387-99.
[http://dx.doi.org/10.1038/nrd.2016.280] [PMID: 28337020]
[48]
Kopelman PG. Obesity as a medical problem. Nature 2000; 404(6778): 635-43.
[http://dx.doi.org/10.1038/35007508] [PMID: 10766250]
[49]
Manco M, Dallapiccola B. Genetics of pediatric obesity. Pediatrics 2012; 130(1): 123-33.
[http://dx.doi.org/10.1542/peds.2011-2717] [PMID: 22665408]
[50]
Chung WK. An overview of mongenic and syndromic obesities in humans. Pediatr Blood Cancer 2012; 58(1): 122-8.
[http://dx.doi.org/10.1002/pbc.23372] [PMID: 21994130]
[51]
Ng MCY, Bowden DW. Is genetic testing of value in predicting and treating obesity? N C Med J 2013; 74(6): 530-3.
[http://dx.doi.org/10.18043/ncm.74.6.530] [PMID: 24316784]
[52]
Li S, Zhao JH, Luan J, et al. Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. Am J Clin Nutr 2010; 91(1): 184-90.
[http://dx.doi.org/10.3945/ajcn.2009.28403] [PMID: 19812171]
[53]
den Hoed M, Ekelund U, Brage S, et al. Genetic susceptibility to obesity and related traits in childhood and adolescence: Influence of loci identified by genome-wide association studies. Diabetes 2010; 59(11): 2980-8.
[http://dx.doi.org/10.2337/db10-0370] [PMID: 20724581]
[54]
Mahmoud R, Kimonis V, Butler MG. Genetics of obesity in humans: A clinical review. Int J Mol Sci 2022; 23(19): 11005.
[http://dx.doi.org/10.3390/ijms231911005] [PMID: 36232301]
[55]
Münzberg H, Morrison CD. Structure, production and signaling of leptin. Metabolism 2015; 64(1): 13-23.
[http://dx.doi.org/10.1016/j.metabol.2014.09.010] [PMID: 25305050]
[56]
Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973; 9(4): 294-8.
[http://dx.doi.org/10.1007/BF01221857] [PMID: 4767369]
[57]
Coleman DL. Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 1978; 14(3): 141-8.
[http://dx.doi.org/10.1007/BF00429772] [PMID: 350680]
[58]
Friedman JM, Leibel RL. Tackling a weighty problem. Cell 1992; 69(2): 217-20.
[http://dx.doi.org/10.1016/0092-8674(92)90402-X] [PMID: 1568242]
[59]
Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395(6704): 763-70.
[http://dx.doi.org/10.1038/27376] [PMID: 9796811]
[60]
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372(6505): 425-32.
[http://dx.doi.org/10.1038/372425a0] [PMID: 7984236]
[61]
Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269(5223): 540-3.
[http://dx.doi.org/10.1126/science.7624776] [PMID: 7624776]
[62]
Sadaf Farooqi I. Genetic and hereditary aspects of childhood obesity. Best Pract Res Clin Endocrinol Metab 2005; 19(3): 359-74.
[http://dx.doi.org/10.1016/j.beem.2005.04.004] [PMID: 16150380]
[63]
Franks PW, Brage S, Luan JA, et al. Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obes Res 2005; 13(8): 1476-84.
[http://dx.doi.org/10.1038/oby.2005.178] [PMID: 16129731]
[64]
Paracchini V, Pedotti P, Taioli E. Genetics of leptin and obesity: A huge review. Am J Epidemiol 2005; 162(2): 101-14.
[http://dx.doi.org/10.1093/aje/kwi174] [PMID: 15972940]
[65]
Wasim M, Awan FR, Najam SS, Khan AR, Khan HN. Role of leptin deficiency, inefficiency, and leptin receptors in obesity. Biochem Genet 2016; 54(5): 565-72.
[http://dx.doi.org/10.1007/s10528-016-9751-z] [PMID: 27313173]
[66]
Obradovic M, Sudar-Milovanovic E, Soskic S, et al. Leptin and obesity: Role and clinical implication. Front Endocrinol 2021; 12: 585887.
[http://dx.doi.org/10.3389/fendo.2021.585887] [PMID: 34084149]
[67]
Chen H, Charlat O, Tartaglia LA, et al. Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996; 84(3): 491-5.
[http://dx.doi.org/10.1016/S0092-8674(00)81294-5] [PMID: 8608603]
[68]
Roh J, Lee J, Park SU, et al. CRISPR-Cas9-mediated generation of obese and diabetic mouse models. Exp Anim 2018; 67(2): 229-37.
[http://dx.doi.org/10.1538/expanim.17-0123] [PMID: 29343656]
[69]
Kamble PG, Hetty S, Vranic M, et al. Proof-of-concept for CRISPR/Cas9 gene editing in human preadipocytes: Deletion of FKBP5 and PPARG and effects on adipocyte differentiation and metabolism. Sci Rep 2020; 10(1): 10565.
[http://dx.doi.org/10.1038/s41598-020-67293-y] [PMID: 32601291]
[70]
Liu J, Liu J, Zeng D, et al. miR-143-null is against diet-induced obesity by promoting BAT thermogenesis and inhibiting WAT adipogenesis. Int J Mol Sci 2022; 23(21): 13058.
[http://dx.doi.org/10.3390/ijms232113058] [PMID: 36361843]
[71]
Wang CH, Lundh M, Fu A, et al. CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice. Sci Transl Med 2020; 12(558): eaaz8664.
[http://dx.doi.org/10.1126/scitranslmed.aaz8664] [PMID: 32848096]
[72]
Qiu J, Bosch MA, Stincic TL, et al. CRISPR/SaCas9 mutagenesis of stromal interaction molecule 1 in proopiomelanocortin neurons increases glutamatergic excitability and protects against diet-induced obesity. Mol Metab 2022; 66: 101645.
[http://dx.doi.org/10.1016/j.molmet.2022.101645] [PMID: 36442744]
[73]
Yang Z, Li P, Shang Q, et al. CRISPR-mediated BMP9 ablation promotes liver steatosis via the down-regulation of PPARα expression. Sci Adv 2020; 6(48): eabc5022.
[http://dx.doi.org/10.1126/sciadv.abc5022] [PMID: 33246954]
[74]
Leuillier M, Duflot T, Ménoret S, et al. CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury. J Adv Res 2023; 43: 163-74.
[http://dx.doi.org/10.1016/j.jare.2022.03.004] [PMID: 36585106]
[75]
Zhu L, Yang X, Li J, et al. Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system. J Genet Genomics 2021; 48(2): 134-46.
[http://dx.doi.org/10.1016/j.jgg.2021.01.008] [PMID: 33931338]
[76]
Tian H, Niu H, Luo J, et al. Effects of CRISPR/Cas9-mediated stearoyl-Coenzyme A desaturase 1 knockout on mouse embryo development and lipid synthesis. PeerJ 2022; 10: e13945.
[http://dx.doi.org/10.7717/peerj.13945] [PMID: 36124130]
[77]
Tsagkaraki E, Nicoloro SM, DeSouza T, et al. CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease. Nat Commun 2021; 12(1): 6931.
[http://dx.doi.org/10.1038/s41467-021-27190-y] [PMID: 34836963]
[78]
Yuan H, Ruan Y, Tan Y, et al. Regenerating Urethral Striated muscle by CRISPRi/dCas9-KRAB-mediated myostatin silencing for obesity-associated stress urinary incontinence. CRISPR J 2020; 3(6): 562-72.
[http://dx.doi.org/10.1089/crispr.2020.0077] [PMID: 33346712]
[79]
Lin X, Liou YH, Li Y, et al. FAM13A represses AMPK activity and regulates hepatic glucose and lipid metabolism. iScience 2020; 23(3): 100928.
[http://dx.doi.org/10.1016/j.isci.2020.100928] [PMID: 32151973]
[80]
Lundbäck V, Kulyte A, Strawbridge RJ, et al. FAM13A and POM121C are candidate genes for fasting insulin: Functional follow-up analysis of a genome-wide association study. Diabetologia 2018; 61(5): 1112-23.
[http://dx.doi.org/10.1007/s00125-018-4572-8] [PMID: 29487953]
[81]
Le Magueresse-Battistoni B. Adipose tissue and endocrine-disrupting chemicals: Does sex matter? Int J Environ Res Public Health 2020; 17(24): 9403.
[http://dx.doi.org/10.3390/ijerph17249403] [PMID: 33333918]
[82]
Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89(6): 2548-56.
[http://dx.doi.org/10.1210/jc.2004-0395] [PMID: 15181022]
[83]
Guerreiro VA, Carvalho D, Freitas P. Obesity, adipose tissue, and inflammation answered in questions. J Obes 2022; 2022: 1-11.
[http://dx.doi.org/10.1155/2022/2252516] [PMID: 35321537]
[84]
Gupta A, Efthymiou V, Kodani SD, et al. Mapping the transcriptional landscape of human white and brown adipogenesis using single-nuclei RNA-seq. Mol Metab 2023; 74: 101746.
[http://dx.doi.org/10.1016/j.molmet.2023.101746] [PMID: 37286033]
[85]
Gezginci-Oktayoglu S, Sancar S, Karatug-Kacar A, Bolkent S. miR-375 induces adipogenesis through targeting Erk1 in pancreatic duct cells under the influence of sodium palmitate. J Cell Physiol 2021; 236(5): 3881-95.
[http://dx.doi.org/10.1002/jcp.30129] [PMID: 33107061]
[86]
Chen C, Zhang X, Deng Y, et al. Regulatory roles of circRNAs in adipogenesis and lipid metabolism: Emerging insights into lipid-related diseases. FEBS J 2021; 288(12): 3663-82.
[http://dx.doi.org/10.1111/febs.15525] [PMID: 32798313]
[87]
Becher T, Palanisamy S, Kramer DJ, et al. Brown adipose tissue is associated with cardiometabolic health. Nat Med 2021; 27(1): 58-65.
[http://dx.doi.org/10.1038/s41591-020-1126-7] [PMID: 33398160]
[88]
Nedergaard J, Cannon B. The changed metabolic world with human brown adipose tissue: Therapeutic visions. Cell Metab 2010; 11(4): 268-72.
[http://dx.doi.org/10.1016/j.cmet.2010.03.007] [PMID: 20374959]
[89]
Carpentier AC, Blondin DP, Haman F, Richard D. Brown adipose tissue-a translational perspective. Endocr Rev 2023; 44(2): 143-92.
[http://dx.doi.org/10.1210/endrev/bnac015] [PMID: 35640259]
[90]
Chen Z, Wang GX, Ma SL, et al. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders. Mol Metab 2017; 6(8): 863-72.
[http://dx.doi.org/10.1016/j.molmet.2017.03.016] [PMID: 28752050]
[91]
Wang GX, Zhao XY, Meng ZX, et al. The brown fat–enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med 2014; 20(12): 1436-43.
[http://dx.doi.org/10.1038/nm.3713] [PMID: 25401691]
[92]
Harb E, Kheder O, Poopalasingam G,  Rashid R,  Srinivasan A, Izzi-Engbeaya C. Brown adipose tissue and regulation of human body weight. Diabetes Metab Res Rev 2023; 39(1): e3594.
[http://dx.doi.org/10.1002/dmrr.3594] [PMID: 36398906]
[93]
Cannon B, de Jong JMA, Fischer AW, Nedergaard J, Petrovic N. Human brown adipose tissue: Classical brown rather than brite/beige? Exp Physiol 2020; 105(8): 1191-200.
[http://dx.doi.org/10.1113/EP087875] [PMID: 32378255]
[94]
Townsend KL, Tseng YH. Brown fat fuel utilization and thermogenesis. Trends Endocrinol Metab 2014; 25(4): 168-77.
[http://dx.doi.org/10.1016/j.tem.2013.12.004] [PMID: 24389130]
[95]
Zhang Y, Yin C, Zhang T, et al. CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs. Sci Rep 2015; 5(1): 16277.
[http://dx.doi.org/10.1038/srep16277] [PMID: 26538064]
[96]
Vora S, Tuttle M, Cheng J, Church G. Next stop for the CRISPR revolution: RNA-guided epigenetic regulators. FEBS J 2016; 283(17): 3181-93.
[http://dx.doi.org/10.1111/febs.13768] [PMID: 27248712]
[97]
Xiong K, Zhou Y, Hyttel P, Bolund L, Freude KK, Luo Y. Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM). Stem Cell Res 2016; 17(3): 665-9.
[http://dx.doi.org/10.1016/j.scr.2016.10.011] [PMID: 27934604]
[98]
Chen X, Ranjan VD, Liu S, et al. In situ formation of 3D conductive and cell-laden graphene hydrogel for electrically regulating cellular behavior. Macromol Biosci 2021; 21(4): 2000374.
[http://dx.doi.org/10.1002/mabi.202000374] [PMID: 33620138]
[99]
Tozzi A, Bengtson CP, Longone P, et al. Involvement of transient receptor potential-like channels in responses to mGluR-I activation in midbrain dopamine neurons. Eur J Neurosci 2003; 18(8): 2133-45.
[http://dx.doi.org/10.1046/j.1460-9568.2003.02936.x] [PMID: 14622174]
[100]
Clapham DE. TRP channels as cellular sensors. Nature 2003; 426(6966): 517-24.
[http://dx.doi.org/10.1038/nature02196] [PMID: 14654832]
[101]
Salido GM, Jardín I, Rosado JA. The TRPC ion channels: Association with Orai1 and STIM1 proteins and participation in capacitative and non-capacitative calcium entry. Transient Recep Potential Channels 2011; pp. 413-33.
[102]
Ling M, Lai X, Quan L, et al. Knockdown of VEGFB/VEGFR1 signaling promotes white adipose tissue browning and skeletal muscle development. Int J Mol Sci 2022; 23(14): 7524.
[http://dx.doi.org/10.3390/ijms23147524] [PMID: 35886871]
[103]
Chen L, Dai YM, Ji CB, et al. MiR-146b is a regulator of human visceral preadipocyte proliferation and differentiation and its expression is altered in human obesity. Mol Cell Endocrinol 2014; 393(1-2): 65-74.
[http://dx.doi.org/10.1016/j.mce.2014.05.022] [PMID: 24931160]
[104]
Kawamura Y, Tanaka Y, Kawamori R, Maeda S. Overexpression of Kruppel-like factor 7 regulates adipocytokine gene expressions in human adipocytes and inhibits glucose-induced insulin secretion in pancreatic β-cell line. Mol Endocrinol 2006; 20(4): 844-56.
[http://dx.doi.org/10.1210/me.2005-0138] [PMID: 16339272]
[105]
Sun Y, Xu H, Li J, et al. Genome-wide survey identifies TNNI2 as a target of KLF7 that inhibits chicken adipogenesis via downregulating FABP4. Biochim Biophys Acta Gene Regul Mech 2023; 1866(1): 194899.
[http://dx.doi.org/10.1016/j.bbagrm.2022.194899] [PMID: 36410687]
[106]
Zhang Z, Wang H, Sun Y, Li H, Wang N. Klf7 modulates the differentiation and proliferation of chicken preadipocyte. Acta Biochim Biophys Sin 2013; 45(4): 280-8.
[http://dx.doi.org/10.1093/abbs/gmt010] [PMID: 23439665]
[107]
Jia Z. KLF7 promotes preadipocyte proliferation via activation of the akt signaling pathway by cis-regulating CDKN3. bioRxiv 2022; 2022.06.
[http://dx.doi.org/10.1101/2022.06.16.496506]
[108]
Newman JW, Morisseau C, Harris TR, Hammock BD. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci USA 2003; 100(4): 1558-63.
[http://dx.doi.org/10.1073/pnas.0437724100] [PMID: 12574510]
[109]
Cronin A, Mowbray S, Dürk H, et al. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc Natl Acad Sci USA 2003; 100(4): 1552-7.
[http://dx.doi.org/10.1073/pnas.0437829100] [PMID: 12574508]
[110]
Gonçalves GAR, Paiva RMA. Gene therapy: Advances, challenges and perspectives. Einstein 2017; 15(3): 369-75.
[http://dx.doi.org/10.1590/s1679-45082017rb4024] [PMID: 29091160]
[111]
Gao M, Liu D. Gene therapy for obesity: Progress and prospects. Discov Med 2014; 17(96): 319-28.
[PMID: 24979252]
[112]
Song Z, Xiaoli A, Yang F. Regulation and metabolic significance of de novo lipogenesis in adipose tissues. Nutrients 2018; 10(10): 1383.
[http://dx.doi.org/10.3390/nu10101383] [PMID: 30274245]
[113]
Akalestou E, Genser L, Rutter GA. Glucocorticoid metabolism in obesity and following weight loss. Front Endocrinol 2020; 11: 59.
[http://dx.doi.org/10.3389/fendo.2020.00059] [PMID: 32153504]
[114]
Wei X, Zhang J, Tang M, Wang X, Fan N, Peng Y. Fat mass and obesity–associated protein promotes liver steatosis by targeting PPARα. Lipids Health Dis 2022; 21(1): 29.
[http://dx.doi.org/10.1186/s12944-022-01640-y] [PMID: 35282837]
[115]
Salazar VS, Gamer LW, Rosen V. BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol 2016; 12(4): 203-21.
[http://dx.doi.org/10.1038/nrendo.2016.12] [PMID: 26893264]
[116]
Miller AF, Harvey SAK, Thies RS, Olson MS. Bone morphogenetic protein-9. An autocrine/paracrine cytokine in the liver. J Biol Chem 2000; 275(24): 17937-45.
[http://dx.doi.org/10.1074/jbc.275.24.17937] [PMID: 10849432]
[117]
Bidart M, Ricard N, Levet S, et al. BMP9 is produced by hepatocytes and circulates mainly in an active mature form complexed to its prodomain. Cell Mol Life Sci 2012; 69(2): 313-24.
[http://dx.doi.org/10.1007/s00018-011-0751-1] [PMID: 21710321]
[118]
Huang C, Chen W, Wang X. Studies on the fat mass and obesity-associated (FTO) gene and its impact on obesity-associated diseases. Genes Dis 2023; 10(6): 2351-65.
[http://dx.doi.org/10.1016/j.gendis.2022.04.014] [PMID: 37554175]
[119]
Claussnitzer M, Dankel SN, Kim KH, et al. FTO obesity variant circuitry and adipocyte browning in humans. N Engl J Med 2015; 373(10): 895-907.
[http://dx.doi.org/10.1056/NEJMoa1502214] [PMID: 26287746]
[120]
Chung JY, Hong J, Kim HJ, et al. White adipocyte-targeted dual gene silencing of FABP4/5 for anti-obesity, anti-inflammation and reversal of insulin resistance: Efficacy and comparison of administration routes. Biomaterials 2021; 279: 121209.
[http://dx.doi.org/10.1016/j.biomaterials.2021.121209] [PMID: 34700224]
[121]
Chen MT, Huang JS, Gao DD, Li YX, Wang HY. Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice. Basic Clin Pharmacol Toxicol 2021; 129(3): 173-82.
[http://dx.doi.org/10.1111/bcpt.13621] [PMID: 34128319]
[122]
Furuhashi M. Fatty acid-binding protein 4 in cardiovascular and metabolic diseases. J Atheroscler Thromb 2019; 26(3): 216-32.
[http://dx.doi.org/10.5551/jat.48710] [PMID: 30726793]
[123]
Chung JY, Ain QU, Song Y, Yong SB, Kim YH. Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance. Genome Res 2019; 29(9): 1442-52.
[http://dx.doi.org/10.1101/gr.246900.118] [PMID: 31467027]
[124]
Lu Y, Day FR, Gustafsson S, et al. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk. Nat Commun 2016; 7(1): 10495.
[http://dx.doi.org/10.1038/ncomms10495] [PMID: 26833246]
[125]
Kilpeläinen TO, Zillikens MC, Stančákova A, et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 2011; 43(8): 753-60.
[http://dx.doi.org/10.1038/ng.866] [PMID: 21706003]
[126]
Cook NL, Pjanic M, Emmerich AG, et al. CRISPR-Cas9-mediated knockout of SPRY2 in human hepatocytes leads to increased glucose uptake and lipid droplet accumulation. BMC Endocr Disord 2019; 19(1): 115.
[http://dx.doi.org/10.1186/s12902-019-0442-8] [PMID: 31664995]
[127]
He Y, Brouwers B, Liu H, et al. Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior. Nat Med 2022; 28(12): 2537-46.
[http://dx.doi.org/10.1038/s41591-022-02106-5] [PMID: 36536256]

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