{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:04:17Z","timestamp":1782345857675,"version":"3.54.5"},"reference-count":32,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["PO1HL51971"],"award-info":[{"award-number":["PO1HL51971"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","doi-asserted-by":"publisher","award":["P20GM104357"],"award-info":[{"award-number":["P20GM104357"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","doi-asserted-by":"publisher","award":["U54GM115428"],"award-info":[{"award-number":["U54GM115428"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2018,4,1]]},"abstract":"<jats:p> Although central melanocortin 4 receptor (MC4R) blockade abolishes the central nervous system (CNS)-mediated anorexogenic, antidiabetic, and cardiovascular actions of leptin, chronic MC4R stimulation fails to completely mimic the effects of leptin. Because neuropeptide Y (NPY) and MC4R exert opposite effects on cardiovascular and metabolic functions, we tested the role of NPY in offsetting the long-term actions of MC4R activation. Wild-type (WT) and NPY-deficient (NPY<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were implanted with telemetry probes for measuring mean arterial pressure (MAP) and heart rate (HR) 24 h\/day. After the mice recovered from surgery and stable baseline measurements, the MC3\/4R agonist melanotan II (MTII, 120 \u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> iv) was infused for 7 days followed by a recovery period. No major differences between groups were observed at baseline except for slightly higher food intake and HR in NPY<jats:sup>\u2212\/\u2212<\/jats:sup> mice (4.3\u2009\u00b1\u20090.2 vs. 3.4\u2009\u00b1\u20090.2 g\/day and 567\u2009\u00b1\u200914 vs. 522\u2009\u00b1\u200913 beats\/min). Chronic MTII infusion reduced food intake in both groups while causing transient increases in MAP and HR only in WT mice (peaks of 11\u2009\u00b1\u20093 mmHg and 126\u2009\u00b1\u200913 beats\/min). To examine whether NPY deficiency would amplify the antidiabetic effects of MC4R activation, diabetes was induced with streptozotocin (STZ) 1 wk before baseline measurements were taken, and the same experimental protocol was followed. In WT and NPY<jats:sup>\u2212\/\u2212<\/jats:sup> mice, STZ-induced diabetes led to similar hyperphagia, hyperglycemia, and weight loss, which were not reversed by chronic MTII treatment. Our results demonstrate that chronic MC4R activation, even in NPY-deficient mice, does not mimic chronic antidiabetic, cardiovascular, or metabolic actions of leptin, and that NPY is not essential for hyperphagia or cardiovascular changes associated with diabetes. <\/jats:p>","DOI":"10.1152\/ajpregu.00293.2017","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T13:46:09Z","timestamp":1515419169000},"page":"R533-R539","source":"Crossref","is-referenced-by-count":10,"title":["Control of appetite, blood glucose, and blood pressure during melanocortin-4 receptor activation in normoglycemic and diabetic NPY-deficient mice"],"prefix":"10.1152","volume":"314","author":[{"given":"Alexandre A.","family":"da Silva","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi"},{"name":"Bar\u00e3o de Mau\u00e1 University Center, Ribeir\u00e3o Preto, Sao Paulo, Brazil"},{"name":"Universidade Estadual de Minas Gerais, Passos, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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