{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:16:19Z","timestamp":1791918979562,"version":"4.3.4"},"reference-count":88,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Leptin is a peptide hormone, mainly known for its role as a mediator of adipose tissue endocrine functions, such as appetite control and energy homeostasis. In addition, leptin signaling is involved in several physiological processes as modulation of innate and adaptive immune responses and regulation of sex hormone levels. When adipose tissue expands, an imbalance of adipokines secretion may occur and increasing leptin levels contribute to promoting a chronic inflammatory state, which is largely acknowledged as a hallmark of cancer. Indeed, upon binding its receptor (LEPR), leptin activates several oncogenic pathways, such as JAK\/STAT, MAPK, and PI3K\/AKT, and seems to affect cancer immune response by inducing a proinflammatory immune polarization and eventually enhancing T-cell exhaustion. In particular, obesity-associated hyperleptinemia has been related to breast cancer risk development, although the underlying mechanism is yet to be completely clarified and needs to be deemed in light of multiple variables, such as menopausal state and immune response. The aim of this review is to provide an overview of the potential role of leptin as a bridge between obesity and breast cancer and to establish the physio-pathological basis of the linkage between these major health concerns in order to identify appropriate and novel therapeutic strategies to adopt in daily clinical practice.<\/jats:p>","DOI":"10.3390\/biom12101394","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T21:03:10Z","timestamp":1664485390000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Insight on the Role of Leptin: A Bridge from Obesity to Breast Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-3224","authenticated-orcid":false,"given":"Roberto","family":"Buonaiuto","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2463-8952","authenticated-orcid":false,"given":"Fabiana","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Parola","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"De Placido","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Forestieri","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Pecoraro","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-224X","authenticated-orcid":false,"given":"Alberto","family":"Servetto","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7205-5105","authenticated-orcid":false,"given":"Luigi","family":"Formisano","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-6870","authenticated-orcid":false,"given":"Pietro","family":"Formisano","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Arpino","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabino","family":"De Placido","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/cac2.12207","article-title":"Global patterns of breast cancer incidence and mortality: A population-based cancer registry data analysis from 2000 to 2020","volume":"41","author":"Lei","year":"2021","journal-title":"Cancer Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s00394-021-02739-1","article-title":"Nutritional status, lifestyle habits and cancer mortality: A population-based prospective cohort study","volume":"61","author":"Wu","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_4","unstructured":"World Health Organization (2021, August 19). WHO Discussion Paper: Draft Recommendations for the Prevention and Management of Obesity over the Life Course, Including Potential Targets. Available online: https:\/\/www.who.int\/publications\/m\/item\/who-discussion-paper-draft-recommendations-for-the-prevention-and-management-of-obesity-over-the-life-course-including-potential-targets."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"799","DOI":"10.4093\/dmj.2021.0077","article-title":"Obesity, Diabetes, and Increased Cancer Progression","volume":"45","author":"Kim","year":"2021","journal-title":"Diabetes Metab. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.5114\/aoms.2013.33181","article-title":"Biochemistry of adipose tissue: An endocrine organ","volume":"9","author":"Coelho","year":"2013","journal-title":"Arch. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Makki, K., Froguel, P., and Wolowczuk, I. (2013). Adipose tissue in obesity-related inflammation and insulin resistance: Cells, cytokines, and chemokines. Int. Sch. Res. Not., 2013.","DOI":"10.1155\/2013\/139239"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1200\/JCO.2016.67.4283","article-title":"Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation","volume":"34","author":"Iyengar","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"545","DOI":"10.2217\/17460875.3.5.545","article-title":"Macrophage infiltration into adipose tissue: Initiation, propagation and remodeling","volume":"3","author":"Surmi","year":"2008","journal-title":"Future Lipidol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1194\/jlr.M500294-JLR200","article-title":"Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans","volume":"46","author":"Cinti","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1194\/jlr.M800019-JLR200","article-title":"Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice","volume":"49","author":"Murano","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1158\/1940-6207.CAPR-11-0110","article-title":"Inflammation and Increased Aromatase Expression Occur in the Breast Tissue of Obese Women with Breast Cancer","volume":"4","author":"Morris","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"D\u2019Esposito, V., Ambrosio, M.R., Giuliano, M., Cabaro, S., Miele, C., Beguinot, F., and Formisano, P. (2020). Mammary Adipose Tissue Control of Breast Cancer Progression: Impact of Obesity and Diabetes. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01554"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109000","DOI":"10.18632\/oncotarget.22552","article-title":"Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells","volume":"8","author":"Ambrosio","year":"2017","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24495","DOI":"10.18632\/oncotarget.8336","article-title":"Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5","volume":"7","author":"Liguoro","year":"2016","journal-title":"Oncotarget"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00239-002-2385-2","article-title":"Phylogeny of a Growth Hormone-Like Cytokine Superfamily Based upon 3D Structure","volume":"56","author":"Ouyang","year":"2003","journal-title":"J. Mol. Evol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Jim\u00e9nez, F., P\u00e9rez, A.P., de la Cruz-Merino, L., and S\u00e1nchez-Margalet, V. (2019). Obesity and Breast Cancer: Role of Leptin. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00596"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1098\/rstb.2006.1859","article-title":"Appetite and energy balance signals from adipocytes","volume":"361","author":"Trayhurn","year":"2006","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1210\/me.2015-1232","article-title":"Minireview: CNS Mechanisms of Leptin Action","volume":"30","author":"Flak","year":"2016","journal-title":"Mol. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/MED.0000000000000184","article-title":"Leptin Applications in 2015: What Have We Learned about Leptin and Obesity?","volume":"22","author":"Farr","year":"2015","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.cmet.2019.08.005","article-title":"Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy","volume":"30","author":"Zhao","year":"2019","journal-title":"Cell Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1210\/en.2004-0032","article-title":"Minireview: A Hypothalamic Role in Energy Balance with Special Emphasis on Leptin","volume":"145","author":"Sahu","year":"2004","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1080\/23328940.2017.1327003","article-title":"The role of leptin in health and disease","volume":"4","author":"Donato","year":"2017","journal-title":"Temperature"},{"key":"ref_24","first-page":"E567","article-title":"Leptin in human physiology and pathophysiology","volume":"301","author":"Mantzoros","year":"2011","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/0092-8674(95)90151-5","article-title":"Identification and expression cloning of a leptin receptor, OB-R","volume":"83","author":"Tartaglia","year":"1995","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2337\/diabetes.50.2.425","article-title":"Transgenic Complementation of Leptin-Receptor Deficiency. I. Rescue of the Obesity\/Diabetes Phenotype of LEPR-Null Mice Expressing a LEPR-B Transgene","volume":"50","author":"Kowalski","year":"2001","journal-title":"Diabetes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1006\/bbrc.2001.4885","article-title":"Soluble Leptin Receptor Represents the Main Leptin Binding Activity in Human Blood","volume":"283","author":"Lammertab","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Cortegana, C., L\u00f3pez-Saavedra, A., S\u00e1nchez-Jim\u00e9nez, F., P\u00e9rez-P\u00e9rez, A., Casti\u00f1eiras, J., Virizuela-Echaburu, J.A., de la Cruz-Merino, L., and S\u00e1nchez-Margalet, V. (2021). Leptin, Both Bad and Good Actor in Cancer. Biomolecules, 11.","DOI":"10.3390\/biom11060913"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/sj.bjc.6604913","article-title":"Circulating levels of leptin, adiposity and breast cancer risk","volume":"100","author":"Wu","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gu, L., Wang, C.-D., Cao, C., Cai, L.-R., Li, D.-H., and Zheng, Y.-Z. (2019). Association of serum leptin with breast cancer. Medicine, 98.","DOI":"10.1097\/MD.0000000000014094"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pan, H., Deng, L.-L., Cui, J.-Q., Shi, L., Yang, Y.-C., Luo, J.-H., Qin, D., and Wang, L. (2018). Association between Serum Leptin Levels and Breast Cancer Risk: An Updated Systematic Review and Meta-Analysis. Medicine, 97.","DOI":"10.1097\/MD.0000000000011345"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"The Premenopausal Breast Cancer Collaborative Group, Schoemaker, M.J., Nichols, H.B., Wright, L.B., Brook, M.N., Jones, M.E., O\u2019Brien, K.M., Adami, H.-O., Baglietto, L., and Bernstein, L. (2018). Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women. JAMA Oncol., 4.","DOI":"10.1001\/jamaoncol.2018.1771"},{"key":"ref_33","first-page":"567","article-title":"Models of breast cancer show that risk is set by events of early life: Prevention efforts must shift focus","volume":"4","author":"Colditz","year":"1995","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_34","first-page":"186","article-title":"Priorities for the primary prevention of breast cancer","volume":"64","author":"Colditz","year":"2014","journal-title":"CA: A Cancer J. Clin."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.maturitas.2006.04.020","article-title":"Aromatase and the breast: Regulation and clinical aspects","volume":"54","author":"Miller","year":"2006","journal-title":"Maturitas"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10549-014-3211-4","article-title":"Reduced progesterone levels explain the reduced risk of breast cancer in obese premenopausal women: A new hypothesis","volume":"149","author":"Dowsett","year":"2015","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0277-5379(88)90173-3","article-title":"The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer","volume":"24","author":"Key","year":"1988","journal-title":"Eur. J. Cancer Clin. Oncol."},{"key":"ref_38","first-page":"927","article-title":"Chemoprevention of N-nitroso-N-methylurea-induced mammary cancers by pretreatment with 17 beta-estradiol and progesterone","volume":"74","author":"Grubbs","year":"1985","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_39","first-page":"4993","article-title":"Estrogens, BRCA1, and Breast Cancer","volume":"60","year":"2000","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28668","DOI":"10.1074\/jbc.M301695200","article-title":"Leptin Enhances, via AP-1, Expression of Aromatase in the MCF-7 Cell Line","volume":"278","author":"Catalano","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"And\u00f2, S., Gelsomino, L., Panza, S., Giordano, C., Bonofiglio, D., Barone, I., and Catalano, S. (2019). Obesity, Leptin and Breast Cancer: Epidemiological Evidence and Proposed Mechanisms. Cancers, 11.","DOI":"10.3390\/cancers11010062"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1158\/0008-5472.CAN-06-2890","article-title":"Evidences that Leptin Up-regulates E-Cadherin Expression in Breast Cancer: Effects on Tumor Growth and Progression","volume":"67","author":"Mauro","year":"2007","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1158\/1078-0432.CCR-05-1913","article-title":"Increased Expression of Leptin and the Leptin Receptor as a Marker of Breast Cancer Progression: Possible Role of Obesity-Related Stimuli","volume":"12","author":"Garofalo","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41523-021-00314-9","article-title":"Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB","volume":"7","author":"Nagalingam","year":"2021","journal-title":"NPJ Breast Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.biopha.2012.10.001","article-title":"Leptin attenuates the anti-estrogen effect of tamoxifen in breast cancer","volume":"67","author":"Chen","year":"2013","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Fiorio, E., Mercanti, A., Terrasi, M., Micciolo, R., Remo, A., Auriemma, A., Molino, A., Parolin, V., Di Stefano, B., and Bonetti, F. (2008). Leptin\/HER2 crosstalk in breast cancer: In vitro study and preliminary in vivoanalysis. BMC Cancer, 8.","DOI":"10.1186\/1471-2407-8-305"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9712","DOI":"10.1158\/0008-5472.CAN-08-1952","article-title":"Bidirectional Crosstalk between Leptin and Insulin-like Growth Factor-I Signaling Promotes Invasion and Migration of Breast Cancer Cells via Transactivation of Epidermal Growth Factor Receptor","volume":"68","author":"Saxena","year":"2008","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.cellsig.2010.05.003","article-title":"Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NF\u03baB\/HIF-1\u03b1 activation","volume":"22","author":"Xu","year":"2010","journal-title":"Cell. Signal."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Garonna, E., Botham, K.M., Birdsey, G.M., Randi, A.M., Gonzalez-Perez, R.R., and Wheeler-Jones, C.P.D. (2011). Vascular Endothelial Growth Factor Receptor-2 Couples Cyclo-Oxygenase-2 with Pro-Angiogenic Actions of Leptin on Human Endothelial Cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018823"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"26320","DOI":"10.1074\/jbc.M601991200","article-title":"Leptin Signaling Promotes the Growth of Mammary Tumors and Increases the Expression of Vascular Endothelial Growth Factor (VEGF) and Its Receptor Type Two (VEGF-R2)","volume":"281","author":"Gonzalez","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.molcel.2012.09.003","article-title":"Ligand-Induced Architecture of the Leptin Receptor Signaling Complex","volume":"48","author":"Mancour","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/ng0996-95","article-title":"Leptin activation of Stat3 in the hypothalamus of wild\u2013type and ob\/ob mice but not db\/db mice","volume":"14","author":"Vaisse","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14563","DOI":"10.1074\/jbc.275.19.14563","article-title":"Activation of Downstream Signals by the Long Form of the Leptin Receptor","volume":"275","author":"Banks","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13316","DOI":"10.1074\/jbc.M609798200","article-title":"Leptin-induced Growth Stimulation of Breast Cancer Cells Involves Recruitment of Histone Acetyltransferases and Mediator Complex to CYCLIN D1 Promoter via Activation of Stat3","volume":"282","author":"Saxena","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.bbrc.2010.02.093","article-title":"Leptin upregulates telomerase activity and transcription of human telomerase reverse transcriptase in MCF-7 breast cancer cells","volume":"394","author":"Ren","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cmet.2017.11.001","article-title":"JAK\/STAT3-Regulated Fatty Acid \u03b2-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance","volume":"27","author":"Wang","year":"2018","journal-title":"Cell Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4747","DOI":"10.1074\/jbc.M007439200","article-title":"Divergent Roles of SHP-2 in ERK Activation by Leptin Receptors","volume":"276","author":"Buchholz","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3892\/mmr.2013.1786","article-title":"Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway","volume":"9","author":"Yuan","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"19908","DOI":"10.1074\/jbc.M313191200","article-title":"Leptin Induces, via ERK1\/ERK2 Signal, Functional Activation of Estrogen Receptor \u03b1 in MCF-7 Cells","volume":"279","author":"Catalano","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14715\/cmb\/2017.63.1.1","article-title":"The role of insulin receptor substrate (IRS) proteins in oncogenic transformation","volume":"63","author":"Gorgisen","year":"2017","journal-title":"Cell. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1080\/15384047.2015.1056409","article-title":"Activation of IL-8 via PI3K\/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells","volume":"16","author":"Wang","year":"2015","journal-title":"Cancer Biol. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-016-0446-4","article-title":"Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2","volume":"35","author":"Wei","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s13402-017-0342-8","article-title":"Leptin promotes the migration and invasion of breast cancer cells by upregulating ACAT2","volume":"40","author":"Huang","year":"2017","journal-title":"Cell. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1182\/blood-2009-03-213595","article-title":"Obesity accelerates thymic aging","volume":"114","author":"Yang","year":"2009","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.molmed.2015.12.001","article-title":"Leptin Regulation of Immune Responses","volume":"22","author":"Naylor","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1210\/en.2009-0565","article-title":"Leptin: A Critical Regulator of CD4+ T-cell Polarization in Vitro and in Vivo","volume":"151","author":"Batra","year":"2010","journal-title":"Endocrinology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/j.biochi.2012.05.018","article-title":"Immunological functions of leptin and adiponectin","volume":"94","author":"Carbone","year":"2012","journal-title":"Biochimie"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.4049\/jimmunol.1102835","article-title":"Cutting Edge: Fasting-Induced Hypoleptinemia Expands Functional Regulatory T Cells in Systemic Lupus Erythematosus","volume":"188","author":"Liu","year":"2012","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5253","DOI":"10.4049\/jimmunol.1402996","article-title":"Leptin Receptor Signaling in T Cells Is Required for Th17 Differentiation","volume":"194","author":"Reis","year":"2015","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/oby.20087","article-title":"Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk","volume":"21","author":"Wagner","year":"2012","journal-title":"Obesity"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1365-2249.2012.04670.x","article-title":"T cell-derived leptin contributes to increased frequency of T helper type 17 cells in female patients with Hashimoto\u2019s thyroiditis","volume":"171","author":"Wang","year":"2012","journal-title":"Clin. Exp. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5150","DOI":"10.1073\/pnas.0408995102","article-title":"Leptin increase in multiple sclerosis associates with reduced number of CD4 + CD25 + regulatory T cells","volume":"102","author":"Matarese","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.cmet.2015.09.013","article-title":"Leptin Deficiency Shifts Mast Cells toward Anti-Inflammatory Actions and Protects Mice from Obesity and Diabetes by Polarizing M2 Macrophages","volume":"22","author":"Zhou","year":"2015","journal-title":"Cell Metab."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Gelsomino, L., Naimo, G.D., Malivindi, R., Augimeri, G., Panza, S., Giordano, C., Barone, I., Bonofiglio, D., Mauro, L., and Catalano, S. (2020). Knockdown of Leptin Receptor Affects Macrophage Phenotype in the Tumor Microenvironment Inhibiting Breast Cancer Growth and Progression. Cancers, 12.","DOI":"10.3390\/cancers12082078"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Naik, A., Monjazeb, A.M., and Decock, J. (2019). The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01940"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"319","DOI":"10.2217\/imt.15.12","article-title":"Obesity and cancer immunotherapy toxicity","volume":"7","author":"Mirsoian","year":"2015","journal-title":"Immunotherapy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nrendo.2017.90","article-title":"Adapting to obesity with adipose tissue inflammation","volume":"13","author":"Reilly","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Estevez, L., Gonz\u00e1lez-Mart\u00ednez, S., and Moreno-Bueno, G. (2021). The Leptin Axis and Its Association With the Adaptive Immune System in Breast Cancer. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.784823"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/jnci\/djaa090","article-title":"Body Mass Index and Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer","volume":"113","author":"Floris","year":"2020","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41591-018-0221-5","article-title":"Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade","volume":"25","author":"Wang","year":"2019","journal-title":"Nat. Med."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Cortellini, A., Bersanelli, M., Buti, S., Cannita, K., Santini, D., Perrone, F., Giusti, R., Tiseo, M., Michiara, M., and Di Marino, P. (2019). A multicenter study of body mass index in cancer patients treated with anti-PD-1\/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable. J. Immunother. Cancer, 7.","DOI":"10.1186\/s40425-019-0527-y"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S1470-2045(18)30078-0","article-title":"Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: A retrospective, multicohort analysis","volume":"19","author":"McQuade","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Pingili, A.K., Chaib, M., Sipe, L.M., Miller, E.J., Teng, B., Sharma, R., Yarbro, J.R., Asemota, S., Al Abdallah, Q., and Mims, T.S. (2021). Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer. Cell Rep., 35.","DOI":"10.1016\/j.celrep.2021.109285"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1586\/era.11.109","article-title":"Targeting the leptin receptor: A potential new mode of treatment for breast cancer","volume":"11","author":"Otvos","year":"2011","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1111\/jcmm.12517","article-title":"A novel leptin antagonist peptide inhibits breast cancer growth in vitro and in vivo","volume":"19","author":"Catalano","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Giordano, C., Gelsomino, L., Barone, I., Panza, S., Augimeri, G., Bonofiglio, D., Rovito, D., Naimo, G.D., Leggio, A., and Catalano, S. (2019). Leptin Modulates Exosome Biogenesis in Breast Cancer Cells: An Additional Mechanism in Cell-to-Cell Communication. J. Clin. Med., 8.","DOI":"10.3390\/jcm8071027"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"29947","DOI":"10.18632\/oncotarget.4937","article-title":"Honokiol activates LKB1-miR-34a axis and antagonizes the oncogenic actions of leptin in breast cancer","volume":"6","author":"Avtanski","year":"2015","journal-title":"Oncotarget"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6194","DOI":"10.1158\/0008-5472.CAN-14-1702","article-title":"Vitamin D Suppresses Leptin Stimulation of Cancer Growth through microRNA","volume":"74","author":"Kasiappan","year":"2014","journal-title":"Cancer Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1394\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:41:46Z","timestamp":1760143306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,29]]},"references-count":88,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101394"],"URL":"https:\/\/doi.org\/10.3390\/biom12101394","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,29]]}}}