{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:43Z","timestamp":1785427303534,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R16GM145591"],"award-info":[{"award-number":["R16GM145591"]}]},{"name":"National Institute of Health","award":["R16GM149471"],"award-info":[{"award-number":["R16GM149471"]}]},{"name":"National Institute of Health","award":["R01ES033660"],"award-info":[{"award-number":["R01ES033660"]}]},{"DOI":"10.13039\/100005188","name":"TRDRP","doi-asserted-by":"crossref","award":["T31IP1551"],"award-info":[{"award-number":["T31IP1551"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005188","name":"TRDRP","doi-asserted-by":"crossref","award":["T35IR9444"],"award-info":[{"award-number":["T35IR9444"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006453","name":"Charles R Drew University of Medicine and Science","doi-asserted-by":"crossref","award":["UHI NIMHD S21MD000103"],"award-info":[{"award-number":["UHI NIMHD S21MD000103"]}],"id":[{"id":"10.13039\/100006453","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006453","name":"Charles R Drew University of Medicine and Science","doi-asserted-by":"crossref","award":["U54MD007598"],"award-info":[{"award-number":["U54MD007598"]}],"id":[{"id":"10.13039\/100006453","id-type":"DOI","asserted-by":"crossref"}]},{"award":["UHI NIMHD S21MD000103"],"award-info":[{"award-number":["UHI NIMHD S21MD000103"]}],"id":[{"id":"https:\/\/ror.org\/038x2fh14","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U54MD007598"],"award-info":[{"award-number":["U54MD007598"]}],"id":[{"id":"https:\/\/ror.org\/038x2fh14","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Follistatin (FST) binds to and neutralizes members of the transforming growth factor-beta (TGF-\u03b2) superfamily, thereby regulating diverse physiological processes, including regulation of skeletal muscle, adipose, and bone homeostasis. FST also promotes adipose browning and enhances energy metabolism, leading to improved plasma lipid profiles and metabolic health in mice. Given the emerging association between brown adipose tissue (BAT) activation and reduced atherosclerosis, we investigated the anti-atherogenic potential of FST. Transcriptomic and metabolomic analyses of the Hybrid Mouse Diversity Panel (HMDP) revealed that Fst expression was negatively correlated with aortic lesion area and positively correlated with the expression of multiple adipose browning-associated genes. Adeno-associated viral delivery of Fst (AAV1-FST344) in Ldlr\u2212\/\u2212 mice significantly reduced aortic lesion area, improved plasma lipid profiles, and decreased expression of adhesion (VCAM1) and inflammatory (iNOS, TNF-\u03b1) markers in white adipose tissue (WAT), liver, and heart. Fst gene delivery also markedly increased uncoupling protein 1 (UCP1) expression in WAT, consistent with WAT browning. Integrated correlation analyses of Fst expression with tissue metabolites, together with plasma metabolite\u2013lesion associations identified in the HMDP, implicated the arginase 1 (Arg1)-mediated metabolic pathway as a key regulator of atherogenesis. Consistent with these findings, Arg1 expression was significantly elevated in WAT, liver, and heart of AAV1-FST344-treated mice and in wild-type versus Fst-knockout mouse embryonic fibroblasts (MEFs). Immunostaining localized Arg1 predominantly to CD68+ macrophages in heart and liver. Given recent evidence identifying Arg1 as a novel mediator of efferocytosis, these findings suggest that Arg1 may promote macrophage metabolic reprogramming and resolution of inflammation by enhancing the clearance of apoptotic cells. Furthermore, Fst gene delivery increased the expression of fibroblast growth factor 21 (Fgf21) and adiponectin (AdipoQ) in WAT. Collectively, these findings identify Fst as a novel anti-atherogenic regulator that protects against vascular disease by promoting adipose browning, improving lipid metabolism, and activating Arg1-mediated metabolic pathways.<\/jats:p>","DOI":"10.3390\/cells15131205","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:04:44Z","timestamp":1782986684000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Follistatin Mitigates Atherosclerosis Through Activation of Arginine Metabolism and Adipose Browning"],"prefix":"10.3390","volume":"15","author":[{"given":"Golnaz","family":"Dirakvand","sequence":"first","affiliation":[{"name":"Department of Biology, California State University, Dominguez Hills, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehla","family":"Pervin","sequence":"additional","affiliation":[{"name":"Department of Biology, California State University, Dominguez Hills, Los Angeles, CA 90747, USA"},{"name":"Division of Endocrinology and Metabolism, College of Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90747, USA"},{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3942-5024","authenticated-orcid":false,"given":"Brian","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Biology, California State University, Dominguez Hills, Los Angeles, CA 90747, USA"},{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Biology, California State University, Dominguez Hills, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yohanna","sequence":"additional","affiliation":[{"name":"Department of Biology, California State University, Dominguez Hills, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Grijalva","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyesh K.","family":"Sinha","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-9531","authenticated-orcid":false,"given":"Srinivasa T.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6409-4910","authenticated-orcid":false,"given":"Rajan","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, College of Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90747, USA"},{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90747, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pervin, S., Reddy, S.T., and Singh, R. (2021). Novel Roles of Follistatin\/Myostatin in Transforming Growth Factor-\u03b2 Signaling and Adipose Browning: Potential for Therapeutic Intervention in Obesity Related Metabolic Disorders. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.653179"},{"key":"ref_2","first-page":"20170036","article-title":"Modulation of transforming growth factor-beta\/follistatin signaling and white adipose browning: Therapeutic implications for obesity related disorders","volume":"31","author":"Pervin","year":"2017","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1210\/me.2010-0127","article-title":"Regulation of muscle mass by follistatin and activins","volume":"24","author":"Lee","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1194\/jlr.M039719","article-title":"Follistatin promotes adipocyte differentiation, browning, and energy metabolism","volume":"55","author":"Braga","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1210\/en.2016-1607","article-title":"Follistatin Targets Distinct Pathways to Promote Brown Adipocyte Characteristics in Brown and White Adipose Tissues","volume":"158","author":"Singh","year":"2017","journal-title":"Endocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101703","DOI":"10.1016\/j.molmet.2023.101703","article-title":"Hepatic follistatin increases basal metabolic rate and attenuates diet-induced obesity during hepatic insulin resistance","volume":"71","author":"Tao","year":"2023","journal-title":"Mol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.mcna.2023.04.004","article-title":"Atherosclerotic Disease: Pathogenesis and Approaches to Management","volume":"107","author":"Morrison","year":"2023","journal-title":"Med. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.cell.2022.04.004","article-title":"Atherosclerosis: Recent developments","volume":"185","author":"Bjorkegren","year":"2022","journal-title":"Cell"},{"key":"ref_9","unstructured":"(2021, February 10). Projections of Cardiovascular Disease Prevalence and Costs: 2015\u20132035. Available online: https:\/\/www.heart.org\/-\/media\/Files\/About-Us\/Policy-Research\/Fact-Sheets\/Public-Health-Advocacy\/Projections-of-CVD-Prevalence-and-Costs-2015-2035.pdf?sc_lang=en."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6356","DOI":"10.1038\/ncomms7356","article-title":"Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development","volume":"6","author":"Berbee","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1161\/CIRCRESAHA.115.306647","article-title":"Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis","volume":"118","author":"Hoeke","year":"2016","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ejphar.2017.03.051","article-title":"Targeting white, brown and perivascular adipose tissue in atherosclerosis development","volume":"816","author":"Boon","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5117","DOI":"10.1038\/s41467-022-32658-6","article-title":"Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling","volume":"13","author":"Adachi","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, Z., Zhang, P., Liu, T., Qiu, X., Li, S., and Lin, J.D. (2024). Neuregulin 4 mediates the metabolic benefits of mild cold exposure by promoting beige fat thermogenesis. JCI Insight, 9.","DOI":"10.1172\/jci.insight.172957"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.2967\/jnumed.115.166025","article-title":"Supraclavicular Brown Adipose Tissue 18F-FDG Uptake and Cardiovascular Disease","volume":"57","author":"Takx","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1038\/aps.2013.70","article-title":"\u03b23-Adrenoceptor activation attenuates atherosclerotic plaque formation in ApoE\u2212\/\u2212 mice through lowering blood lipids and glucose","volume":"34","author":"Wang","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.2337\/db09-0349","article-title":"Genetic disruption of myostatin reduces the development of proatherogenic dyslipidemia and atherogenic lesions in Ldlr null mice","volume":"58","author":"Tu","year":"2009","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Esposito, P., Verzola, D., Picciotto, D., Cipriani, L., Viazzi, F., and Garibotto, G. (2021). Myostatin\/Activin-A Signaling in the Vessel Wall and Vascular Calcification. Cells, 10.","DOI":"10.3390\/cells10082070"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1194\/jlr.R066944","article-title":"The Hybrid Mouse Diversity Panel: A resource for systems genetics analyses of metabolic and cardiovascular traits","volume":"57","author":"Lusis","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1101\/gr.099234.109","article-title":"A high-resolution association mapping panel for the dissection of complex traits in mice","volume":"20","author":"Bennett","year":"2010","journal-title":"Genome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100370","DOI":"10.1016\/j.jlr.2023.100370","article-title":"Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis","volume":"64","author":"Chattopadhyay","year":"2023","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1194\/jlr.M076554","article-title":"Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-beta and cholesterol 25-hydroxylase in jejunum","volume":"58","author":"Mukherjee","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1016\/S0022-2275(20)39713-3","article-title":"Quantitation of atherosclerosis in murine models: Correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice","volume":"36","author":"Tangirala","year":"1995","journal-title":"J. Lipid Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jim.2014.05.009","article-title":"Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice","volume":"408","author":"Abram","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1172\/JCI123700","article-title":"Apolipoprotein A-I mimetics mitigate intestinal inflammation in COX2-dependent inflammatory bowel disease model","volume":"129","author":"Meriwether","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/nm.3361","article-title":"Brown and beige fat: Development, function and therapeutic potential","volume":"19","author":"Harms","year":"2013","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cheng, L., Zhang, S., Shang, F., Ning, Y., Huang, Z., He, R., Sun, J., and Dong, S. (2021). Emodin Improves Glucose and Lipid Metabolism Disorders in Obese Mice via Activating Brown Adipose Tissue and Inducing Browning of White Adipose Tissue. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.618037"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.isci.2019.09.011","article-title":"CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells","volume":"20","author":"Sukanta","year":"2019","journal-title":"iScience"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pilkington, A.C., Paz, H.A., and Wankhade, U.D. (2021). Beige Adipose Tissue Identification and Marker Specificity-Overview. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.599134"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36710","DOI":"10.1038\/srep36710","article-title":"Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults","volume":"6","author":"Jiang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7455","DOI":"10.1113\/JP272971","article-title":"The complementary and divergent roles of uncoupling proteins 1 and 3 in thermoregulation","volume":"594","author":"Riley","year":"2016","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0092-8674(00)81410-5","article-title":"A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis","volume":"92","author":"Puigserver","year":"1998","journal-title":"Cell"},{"key":"ref_33","first-page":"1452696","article-title":"PGC-1\u03b1, Inflammation, and Oxidative Stress: An Integrative View in Metabolism","volume":"2020","author":"Ortega","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1089\/ars.2006.1456","article-title":"Effects of PGC-1\u03b1 on TNF-\u03b1\u2013Induced MCP-1 and VCAM-1 Expression and NF-\u03baB Activation in Human Aortic Smooth Muscle and Endothelial Cells","volume":"9","author":"Kim","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/emmm.201302587","article-title":"Macrophage PPAR gamma Co-activator-1 alpha participates in repressing foam cell formation and atherosclerosis in response to conjugated linoleic acid","volume":"5","author":"McCarthy","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12933-016-0441-2","article-title":"Common dysregulated pathways in obese adipose tissue and atherosclerosis","volume":"15","author":"Amor","year":"2016","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6ra15","DOI":"10.1126\/scitranslmed.3000112","article-title":"Follistatin gene delivery enhances muscle growth and strength in nonhuman primates","volume":"1","author":"Kota","year":"2009","journal-title":"Sci. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.ymthe.2017.02.015","article-title":"Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes","volume":"25","author":"Mendell","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.ajpath.2023.12.006","article-title":"Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease","volume":"194","author":"Anand","year":"2024","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1161\/CIRCULATIONAHA.115.015308","article-title":"Fibroblast growth factor 21 prevents atherosclerosis by suppression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice","volume":"131","author":"Lin","year":"2015","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.cmet.2013.03.019","article-title":"An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice","volume":"17","author":"Holland","year":"2013","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Khallou-Laschet, J., Varthaman, A., Fornasa, G., Compain, C., Gaston, A.T., Clement, M., Dussiot, M., Levillain, O., Graff-Dubois, S., and Nicoletti, A. (2010). Macrophage plasticity in experimental atherosclerosis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008852"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38121","DOI":"10.1074\/jbc.M105408200","article-title":"Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities","volume":"276","author":"Razani","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1091\/mbc.E17-01-0049","article-title":"Reciprocal regulation of eNOS and caveolin-1 functions in endothelial cells","volume":"29","author":"Chen","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrendo.2013.204","article-title":"Adipose tissue browning and metabolic health","volume":"10","author":"Bartelt","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/MED.0b013e328337a81f","article-title":"Brown fat as a therapy for obesity and diabetes","volume":"17","author":"Cypess","year":"2010","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1161\/01.RES.85.10.931","article-title":"Human activin-A is expressed in the atherosclerotic lesion and promotes the contractile phenotype of smooth muscle cells","volume":"85","author":"Engelse","year":"1999","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1152\/japplphysiol.90719.2008","article-title":"Elevated levels of activin A in clinical and experimental pulmonary hypertension","volume":"106","author":"Yndestad","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00281-025-01038-9","article-title":"Arginine metabolism in myeloid cells in health and disease","volume":"47","author":"Karadima","year":"2025","journal-title":"Semin. Immunopathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.cmet.2020.01.001","article-title":"Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury","volume":"31","author":"Yurdagul","year":"2020","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/01.ATV.0000195791.83380.4c","article-title":"Identification of Macrophage Arginase I as a New Candidate Gene of Atherosclerosis Resistance","volume":"26","author":"Teupser","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1161\/CIRCRESAHA.111.241810","article-title":"LXRalpha regulates macrophage arginase 1 through PU.1 and interferon regulatory factor 8","volume":"109","author":"Pourcet","year":"2011","journal-title":"Circ. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/eurheartj\/eht329","article-title":"Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation","volume":"35","author":"Wang","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1210\/me.2007-0525","article-title":"Arginase I induction by modified lipoproteins in macrophages: A peroxisome proliferator-activated receptor-gamma\/delta-mediated effect that links lipid metabolism and immunity","volume":"22","author":"Campo","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Fernando, M.R., Reyes, J.L., Iannuzzi, J., Leung, G., and McKay, D.M. (2014). The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094188"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.tcm.2012.10.003","article-title":"Transcriptional regulation of macrophage arginase 1 expression and its role in atherosclerosis","volume":"23","author":"Pourcet","year":"2013","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1210\/me.2005-0331","article-title":"Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77","volume":"20","author":"Pei","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2147\/DMSO.S159315","article-title":"Metabolic profiling of follistatin overexpression: A novel therapeutic strategy for metabolic diseases","volume":"11","author":"Singh","year":"2018","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/apha.12686","article-title":"Crosstalk between adipokines and myokines in fat browning","volume":"219","author":"Rodriguez","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/jmcb\/mjw013","article-title":"The FGF21-adiponectin axis in controlling energy and vascular homeostasis","volume":"8","author":"Hui","year":"2016","journal-title":"J. Mol. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109331","DOI":"10.1016\/j.celrep.2021.109331","article-title":"FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes","volume":"35","author":"Zhang","year":"2021","journal-title":"Cell Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12983","DOI":"10.1074\/jbc.M110.215889","article-title":"Thermogenic activation induces FGF21 expression and release in brown adipose tissue","volume":"286","author":"Hondares","year":"2011","journal-title":"J. Biol. Chem."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T04:51:28Z","timestamp":1783140688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":63,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15131205"],"URL":"https:\/\/doi.org\/10.3390\/cells15131205","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]}}}