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Male and female C57BL\/6 mice were given free access to standard chow and wheat\u2010based foods, including bread and baked wheat flour, and food preference, energy expenditure, hepatic gene expression, and blood metabolite profiles were analyzed. Mice showed a strong preference for wheat\u2010based foods, leading to significant body weight gain despite comparable caloric intake. Wheat flour consumption was associated with reduced energy expenditure, increased adiposity, and elevated circulating insulin and leptin levels. Blood metabolomic analysis revealed increased fatty acid levels and reduced essential amino acids, suggesting enhanced lipogenesis and a potential imbalance in amino acid intake. Consistently, hepatic expression of genes involved in fatty acid synthesis and lipid transport was upregulated. Importantly, withdrawal of wheat flour rapidly attenuated body weight gain and reversed the associated metabolic alterations. These findings demonstrate that wheat flour intake promotes obesity in mice primarily by decreasing energy expenditure and altering metabolic pathways independent of excess calorie consumption, highlighting wheat flour as a dietary factor that strongly influences energy homeostasis and body weight regulation.<\/jats:p>","DOI":"10.1002\/mnfr.70394","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:26:33Z","timestamp":1769153193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Wheat Flour Intake Promotes Weight Gain and Metabolic Changes in Mice"],"prefix":"10.1002","volume":"70","author":[{"given":"Shigenobu","family":"Matsumura","sequence":"first","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miona","family":"Marutani","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Nousou","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagisa","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Mizobata","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyu","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanase","family":"Iki","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoka","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Yamato","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Fujitani","sequence":"additional","affiliation":[{"name":"Center For Hypothalamic Research, Department of Internal Medicine UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teppei","family":"Fujikawa","sequence":"additional","affiliation":[{"name":"Center For Hypothalamic Research, Department of Internal Medicine UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinami","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Takenaka","sequence":"additional","affiliation":[{"name":"Department of Nutrition Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"issue":"2","key":"e_1_2_9_2_1","first-page":"97S","article-title":"The Obesity Epidemic: Pathophysiology and Consequences of Obesity","volume":"10","author":"Pi\u2010Sunyer F. 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