{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T04:46:44Z","timestamp":1791694004887,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008882","name":"Texas State University","doi-asserted-by":"publisher","award":["REP2024"],"award-info":[{"award-number":["REP2024"]}],"id":[{"id":"10.13039\/100008882","id-type":"DOI","asserted-by":"publisher"}]},{"award":["REP2024"],"award-info":[{"award-number":["REP2024"]}],"id":[{"id":"https:\/\/ror.org\/05h9q1g27","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Obesity disrupts glucose homeostasis and insulin signaling, partly through altered gut hormone secretion and intestinal inflammation. Our previous work demonstrated that fructooligosaccharides (FOS), a prebiotic fiber, suppressed colonic inflammation, and modulated gut microbiota when administered with vitamin D supplementation. However, the effects of FOS on metabolic alterations, glucagon-like peptide-1 (GLP-1) production under obesogenic stimulation remains unclear. Here, we examined the effects of FOS on insulin resistance and GLP-1 production in high-fat diet (HFD)\u2014induced obese mice. Methods: Six-week-old male and female C57BL\/6J mice were assigned to control or HFDs \u00b1 5% FOS for 10 weeks. Body weight, visceral fat, fasting glucose, insulin, triglycerides, and insulin resistance index (HOMA-IR) were assessed. Serum GLP-1 was quantified by ELISA. Colonic expressions of Glp1r, Pi3k, and Akt were evaluated by qRT-PCR and western blotting, respectively. Cecal abundance of Akkermansia muciniphila (AM), Dubosiella newyorkensis (DN), and Romboutsia ilealis (RI) was quantified by qPCR. Results: FOS attenuated HFD-induced metabolic dysfunction, lowering serum insulin and HOMA-IR in both sexes. Notably, FOS elicited sex-dependent physical improvements of which it suppressed body weight gain by 10% in male mice and reduced visceral fat accumulation by 36% in female mice. The phenotypic changes in male mice were associated with an increase in GLP-1. Further, FOS modulated colonic PI3K\/Akt signaling in a sex-dependent manner and downregulated HFD-associated increases in Glp1r mRNA expression. Consistent with our previous work, FOS suppressed RI abundance, and this reduction was associated with lower colonic Tlr4 mRNA expression and improved insulin-resistance index. Conclusions: FOS improves insulin sensitivity in HFD-induced obesity and specifically enhanced GLP-1 production in male mice. Though the mechanism remained elucidated, the observed phenotype changes may be attributed to a combination of altered colonic PI3K\/Akt pathways and targeted bacterial shifts. These effects appear to be sex-dependent and support FOS as a promising dietary strategy for maintenance of metabolic health.<\/jats:p>","DOI":"10.3390\/nu18193258","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:14:56Z","timestamp":1790936096000},"page":"3258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dietary Fructooligosaccharide Is Associated with Improved Insulin Resistance, Reduced Romboutsia ilealis Abundance, and Modulation of GLP-1 Production in High-Fat Diet-Induced Obese Mice"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0089-6978","authenticated-orcid":false,"given":"Lais Yuki","family":"Tuzino Kamia","sequence":"first","affiliation":[{"name":"Nutrition and Foods Program, School of Family and Consumer Sciences, College of Applied Arts, Texas State University, San Marcos, TX 78666, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Lewis","sequence":"additional","affiliation":[{"name":"Nutrition and Foods Program, School of Family and Consumer Sciences, College of Applied Arts, Texas State University, San Marcos, TX 78666, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zack","family":"Nobles","sequence":"additional","affiliation":[{"name":"Nutrition and Foods Program, School of Family and Consumer Sciences, College of Applied Arts, Texas State University, San Marcos, TX 78666, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-1723","authenticated-orcid":false,"given":"Gar Yee","family":"Koh","sequence":"additional","affiliation":[{"name":"Nutrition and Foods Program, School of Family and Consumer Sciences, College of Applied Arts, Texas State University, San Marcos, TX 78666, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref_1","unstructured":"World Obesity Federation (2025). 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