{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T07:28:14Z","timestamp":1784273294124,"version":"3.55.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD0087314"],"award-info":[{"award-number":["HD0087314"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Context<\/jats:title>\n<jats:p>Obesity, is a state of chronic inflammation, characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism. We have defined the accompanying decreased Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), ovarian steroids and reduced pituitary response to Gonadotropin-releasing Hormone (GnRH) as Reprometabolic syndrome, a phenotype that can be induced in healthy normal weight women (NWW) by acute infusion of free fatty acids and insulin.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To identify potential mediators of insulin and lipid-related reproductive endocrine dysfunction.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Design, setting, participants<\/jats:title>\n<jats:p>Secondary analysis of crossover study of eumenorrheic reproductive aged women of normal Body Mass Index (BMI) (&lt;25 kg\/m<jats:sup>2<\/jats:sup>) at an academic medical center.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Intervention<\/jats:title>\n<jats:p>Participants underwent 6-hour infusions of either saline\/heparin or insulin plus fatty acids (Intralipid plus heparin), in the early follicular phase of sequential menstrual cycles, in random order. Euglycemia was maintained by glucose infusion. Frequent blood samples were obtained.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Main outcome measures<\/jats:title>\n<jats:p>Pooled serum from each woman was analyzed for cytokines, interleukins, chemokines, adipokines, Fibroblast Growth Factor-21 (FGF-21) and markers of endoplasmic reticulum (ER) stress (CHOP and GRP78). Wilcoxon signed-rank tests were used to compare results across experimental conditions.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec006\">\n<jats:title>Results<\/jats:title>\n<jats:p>Except for Macrophage Inflammatory Protein-1\u03b2 (MIP-1\u03b2), no significant differences were observed in serum levels of any of the inflammatory signaling or ER stress markers tested.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec007\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Acute infusion of lipid and insulin, to mimic the metabolic syndrome of obesity, was not associated with an increase in inflammatory markers. These results imply that the endocrine disruption and adverse reproductive outcomes of obesity are not a consequence of the ambient inflammatory environment but may be mediated by direct lipotoxic effects on the hypothalamic-pituitary-ovarian (HPO) axis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0247638","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T15:41:18Z","timestamp":1616686878000},"page":"e0247638","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["A randomised trial examining inflammatory signaling in acutely induced hyperinsulinemia and hyperlipidemia in normal weight women-the reprometabolic syndrome"],"prefix":"10.1371","volume":"16","author":[{"given":"Andrew","family":"Tannous","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Bradford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-4572","authenticated-orcid":true,"given":"Katherine","family":"Kuhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Fought","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0575-7566","authenticated-orcid":true,"given":"Irene","family":"Schauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9096-7490","authenticated-orcid":true,"given":"Nanette","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"issue":"S1","key":"pone.0247638.ref001","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1002\/2327-6924.12510","article-title":"Obesity: Risk factors, complications, and strategies for sustainable long-term weight management","volume":"29","author":"SM Fruh","year":"2017","journal-title":"J Am Assoc Nurse Pract"},{"key":"pone.0247638.ref002","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S1471-7697(03)00061-3","article-title":"Obesity and infertility","volume":"3","author":"M. 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