{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:54:44Z","timestamp":1789559684874,"version":"build-2803163510"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We examined the effects of 1 month of a eucaloric, high-fat (48% of calories) diet (HFD) on gonadotropin secretion in normal-weight women to interrogate the role of free fatty acids and insulin in mediating the relative hypogonadotropic hypogonadism of obesity. Eighteen eumenorrheic women (body mass index [BMI] 18\u201325\u2005kg\/m2) were studied in the early follicular phase of the menstrual cycle before and after exposure to an HFD with frequent blood sampling for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), followed by an assessment of pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Mass spectrometry-based plasma metabolomic analysis was also performed. Paired testing and time-series analysis were performed as appropriate. Mean endogenous LH (unstimulated) was significantly decreased after the HFD (4.3 \u00b1 1.0 vs. 3.8 \u00b1 1.0, P &amp;lt; 0.01); mean unstimulated FSH was not changed. Both LH (10.1 \u00b1 1.0 vs. 7.2 \u00b1 1.0, P &amp;lt; 0.01) and FSH (9.5 \u00b1 1.0 vs. 8.8 \u00b1 1.0, P &amp;lt; 0.01) responses to 75\u2005ng\/kg of GnRH were reduced after the HFD. Mean LH pulse amplitude and LH interpulse interval were unaffected by the dietary exposure. Eucaloric HFD exposure did not cause weight change. Plasma metabolomics confirmed adherence with elevation of fasting free fatty acids (especially long-chain mono-, poly-, and highly unsaturated fatty acids) by the last day of the HFD. One-month exposure to an HFD successfully induced key reproductive and metabolic features of reprometabolic syndrome in normal-weight women. These data suggest that dietary factors may underlie the gonadotrope compromise seen in obesity-related subfertility and therapeutic dietary interventions, independent of weight loss, may be possible.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad440","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T20:09:34Z","timestamp":1702930174000},"source":"Crossref","is-referenced-by-count":7,"title":["A high-fat eucaloric diet induces reprometabolic syndrome of obesity in normal weight women"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9096-7490","authenticated-orcid":false,"given":"Nanette","family":"Santoro","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado School of Medicine , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-4572","authenticated-orcid":false,"given":"Katherine","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado School of Medicine , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8748-2924","authenticated-orcid":false,"given":"Shannon","family":"Pretzel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado School of Medicine , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0575-7566","authenticated-orcid":false,"given":"Irene E","family":"Schauer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rocky Mountain Regional VA Medical Center , Aurora, CO 80045 , USA"},{"name":"Division of Endocrinology, Metabolism, and Diabetes, University of Colorado School of Medicine , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Fought","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Informatics, Colorado School of Public Health , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-6490","authenticated-orcid":false,"given":"Angelo","family":"D\u2019Alessandro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-571X","authenticated-orcid":false,"given":"Andrew P","family":"Bradford","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Colorado School of Medicine , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"issue":"2","key":"2024013110125651800_pgad440-B1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1093\/humrep\/del400","article-title":"Obesity and time to pregnancy","volume":"22","author":"Gesink Law","year":"2007","journal-title":"Hum Reprod"},{"issue":"2","key":"2024013110125651800_pgad440-B2","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/humrep\/dem371","article-title":"Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women","volume":"23","author":"van der 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