{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:36:15Z","timestamp":1790116575503,"version":"4.0.1"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Diabetes UK RD Lawrence Fellowship"},{"DOI":"10.13039\/501100001632","name":"Ulster University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001632","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Kisspeptin is a neuropeptide recognised for a pivotal role within the reproductive system, but potentially important endocrine metabolic effects are less well understood. We examined effects of twice-daily intraperitoneal administration of saline vehicle or kisspeptin-10 (25 nmol\/kg), for 21 days, on glucose homeostasis, energy balance, circulating hormones as well as the morphology-function of enteroendocrine and islet cells in high-fat diet (HFD) fed female mice, with normal diet (ND) mice as an additional control group. Kisspeptin-10 decreased body weight, blood glucose and energy intake to ND levels. HFD increased circulating follicle-stimulating hormone (FSH) levels, which were further enhanced by kisspeptin-10 along with luteinising hormone (LH) concentrations. Neither HFD nor kisspeptin-10 affected progesterone or corticosterone. In the ileum, kisspeptin-10 decreased crypt depth and restored villi length to ND control levels, as well as increasing the proportion of glucose-dependent insulinotropic polypeptide (GIP) positive cells when compared to HFD mice and glucagon-like peptide-1 (GLP-1) positive cells compared to ND mice. Peptide YY (PYY) immunoreactivity was unaltered by HFD or kisspeptin-10. Plasma GIP was unchanged but circulating GLP-1 and PYY were reduced to ND levels. Within the pancreas, total islet, beta- and alpha-cell areas were similar in all mice, but kisspeptin-10 intervention restored relative insulin area to ND levels. Glucagon radius, an indicator of peripherally located alpha-cells, was reduced in HFD mice but normalised by kisspeptin-10 alongside elevated glucagon-islet area. Notably, beta-cell proliferation was increased by kisspeptin-10 with no alteration in beta-cell apoptosis. Overall, we reveal a previously uncharacterised diverse metabolic role for kisspeptin in directly modulating the gut\u2013pancreatic axis.<\/jats:p>","DOI":"10.3390\/biom15111591","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:59:09Z","timestamp":1763027949000},"page":"1591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Kisspeptin-10 Ameliorates Obesity-Diabetes with Diverse Effects on Ileal Enteroendocrine Cells and Pancreatic Islet Morphology in High-Fat Fed Female Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3865-5067","authenticated-orcid":false,"given":"Ananyaa","family":"Sridhar","sequence":"first","affiliation":[{"name":"Diabetes Research Centre, Biomedical Sciences Research Institute, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-1821","authenticated-orcid":false,"given":"Dawood","family":"Khan","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Biomedical Sciences Research Institute, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rithiga","family":"Muthukumar","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Biomedical Sciences Research Institute, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha","family":"Sampathkumar","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Biomedical Sciences Research Institute, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-964X","authenticated-orcid":false,"given":"Nigel","family":"Irwin","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Biomedical Sciences Research Institute, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Biomedical Sciences Research Institute, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Charlotte","family":"Moffett","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Biomedical Sciences Research Institute, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrendo.2013.203","article-title":"Energy metabolism and fertility\u2014A balance preserved for female health","volume":"10","author":"Torre","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.fertnstert.2024.04.036","article-title":"The impact of obesity on reproductive health and metabolism in reproductive-age females","volume":"122","author":"Schon","year":"2024","journal-title":"Fertil. 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