{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:54:43Z","timestamp":1789559683634,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institute of Health Research (CIHR)","award":["143325"],"award-info":[{"award-number":["143325"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The Western diet (WD) predisposes to bodyweight gain and obesity and is linked to mitochondrial dysfunction, oxidative damage, inflammation, and multisystem disease, even affecting the reproductive organs, fertility, and pregnancy outcomes. In this study, we investigated the effects of multi-ingredient supplementation (MIS) with antioxidants, phytonutrients, and vitamins (\u2018Fertility Enhancer\u2019; FE) on white adipose tissue (WAT) expansion, nonalcoholic fatty liver disease (NAFLD), and infertility in WD-fed C57BL\/6J mice. Five-month-old male (M) and female (F) mice were fed a low-fat diet (LF) or a high fat\/sucrose WD (HF) for six weeks, followed by six weeks of LF (3.64 kcal\/g), HF (4.56 kcal\/g), or HF combined with FE (4.50 kcal\/g). A sub-set of animals were sacrificed at 12 weeks, while the remainder were harem-mated in a 1:2 male-to-female ratio, and singly housed during the gestational period. Two-way, factorial ANOVA analysis revealed a main effect of diet on bodyweight (BW), total body fat, % body fat, white adipose tissue mass, and liver lipid content (all p &lt; 0.001), driven by the anti-obesogenic effects of the \u2018Fertility Enhancer\u2019. Similarly, a main effect of diet was found on PGC1-\u03b1 mRNA levels (p &lt; 0.05) and mitochondrial protein content (p &lt; 0.001) in perigonadal WAT, with PGC1-\u03b1 induction and higher complex II and complex III expression in FE vs. HF animals. Copulatory plug counts were higher in FE vs. HE couples (30% vs. 6%), resulting in more litters (4 vs. 0) and higher copulatory success (67% vs. 0%). Although the trends of all histology outcomes were suggestive of a benefit from the FE diet, only the number of atretic follicles and testicular mass were significant. Ovarian IL-1\u03b2 mRNA induction was significantly attenuated in the FE group (p &lt; 0.05 vs. HF) with CASP1 attenuation trending lower (p = 0.09 vs. HF), which is indicative of anti-inflammatory benefits of the \u2018Fertility Enhancer.\u2019 We conclude that supplementation with specific phytonutrients, antioxidants, and vitamins may have utility as an adjunctive therapy for weight management, fatty liver disease, and infertility in overweight and obese couples.<\/jats:p>","DOI":"10.3390\/nu15030611","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T04:54:41Z","timestamp":1674622481000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5656-5578","authenticated-orcid":false,"given":"Mats I.","family":"Nilsson","sequence":"first","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"},{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"May","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza J.","family":"Roik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Fuda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2927-6372","authenticated-orcid":false,"given":"Ashely","family":"Luo","sequence":"additional","affiliation":[{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P.","family":"Hettinga","sequence":"additional","affiliation":[{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Bujak","sequence":"additional","affiliation":[{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-3746","authenticated-orcid":false,"given":"Mark A.","family":"Tarnopolsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"},{"name":"Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/0002-9343(88)90113-1","article-title":"Stone agers in the fast lane: Chronic degenerative diseases in evolutionary perspective","volume":"84","author":"Eaton","year":"1988","journal-title":"Am. 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