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The excitability of the major output neurons of the olfactory bulb (OB) can be modulated through targeting a voltage\u2010dependent potassium channel, Kv1.3, which responds to changes in metabolic factors such as insulin, glucose, and glucagon\u2010like peptide\u20101. Because gene\u2010targeted deletion or inhibition of Kv1.3 in the periphery has been found to increase energy metabolism and decrease body weight, we hypothesized that inhibition of Kv1.3 selectively in the OB could enhance excitability of the output neurons to evoke changes in energy homeostasis. We thereby employed metal\u2010histidine coordination to self\u2010assemble the Kv1.3 inhibitor margatoxin (MgTx) to fluorescent quantum dots (QDMgTx) as a means to label cells in vivo and test changes in neuronal excitability and metabolism when delivered to the OB. Using patch\u2010clamp electrophysiology to measure Kv1.3 properties in heterologously expressed cells and native mitral cells in OB slices, we found that QDMgTx had a fast rate of inhibition, but with a reduced IC<jats:sub>50,<\/jats:sub> and increased action potential firing frequency. QDMgTx was capable of labeling cloned Kv1.3 channels but was not visible when delivered to native Kv1.3 in the OB. Diet\u2010induced obese mice were observed to reduce body weight and clear glucose more quickly following osmotic mini\u2010pump delivery of QDMgTx\/MgTx to the OB, and following MgTx delivery, they increased the use of fats as fuels (reduced respiratory exchange ratio). These results suggest that enhanced excitability of bulbar output neurons can drive metabolic responses.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15200-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15200","type":"journal-article","created":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T03:15:44Z","timestamp":1601090144000},"page":"1876-1896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Olfactory bulb\u2010targeted quantum dot (QD) bioconjugate and Kv1.3 blocking peptide improve metabolic health in obese male mice"],"prefix":"10.1111","volume":"157","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8059-7577","authenticated-orcid":false,"given":"Austin B.","family":"Schwartz","sequence":"first","affiliation":[{"name":"Institute of Molecular Biophysics The Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-5171","authenticated-orcid":false,"given":"Anshika","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-5500","authenticated-orcid":false,"given":"Zhenbo","family":"Huang","sequence":"additional","affiliation":[{"name":"Program in Neuroscience The Florida State University Tallahassee FL USA"},{"name":"Department of Biological Science The Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2268-6288","authenticated-orcid":false,"given":"Raveendra","family":"Anangi","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4210-791X","authenticated-orcid":false,"given":"John M.","family":"Spear","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The Florida State University Tallahassee FL USA"},{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Stagg","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The Florida State University Tallahassee FL USA"},{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-9551","authenticated-orcid":false,"given":"Erminia","family":"Fardone","sequence":"additional","affiliation":[{"name":"Program in Neuroscience The Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6841-4176","authenticated-orcid":false,"given":"Zolan","family":"Dekan","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2978-3104","authenticated-orcid":false,"given":"Jens T.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"National High Field Magnetic Laboratory The Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-168X","authenticated-orcid":false,"given":"Samuel C.","family":"Grant","sequence":"additional","affiliation":[{"name":"National High Field Magnetic Laboratory The Florida State University Tallahassee FL USA"},{"name":"Department of Chemical &amp; 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