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bioRxiv · 10.64898/2026.01.06.697863

Exacerbation of sucrose-induced visceral obesity and glucose intolerance by ovariectomy and its GLP-1-dependent amelioration by the rare sugar D-allulose

Iba, K.·Kyo, M.·Ishihara, H.·Nagao, A.·Kawabe, M.·Ohbayashi, K.·Yada, T.·Iwasaki, Y.
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Abstract

Estrogen deficiency after menopause promotes visceral fat accumulation and insulin resistance, thereby increasing the risk of type 2 diabetes. Although hormone replacement therapy is partially effective, its use is limited by increased risks of cardiovascular disease and breast cancer, underscoring the need for safer preventive strategies. The rare sugar D-allulose has been reported to stimulate glucagon-like peptide-1 (GLP-1), a gut hormone, secretion and to improve obesity and glucose metabolism, suggesting its potential as a novel intervention for postmenopausal metabolic dysfunction. Here, we examined whether D-allulose improves obesity and glucose intolerance in a GLP-1-dependent manner under sucrose-fed conditions, using ovariectomized (OVX) female C57BL/6J mice as a model of menopause. OVX mice, but not sucrose-fed sham mice, developed exacerbated visceral obesity and glucose intolerance in response to dietary sucrose, despite similar total energy intake. Daily oral administration of D-allulose for two weeks significantly suppressed visceral fat accumulation, improved insulin resistance, and ameliorated glucose intolerance in sucrose-fed OVX mice. These beneficial effects were markedly attenuated in GLP-1 receptor knockout mice. Taken together, we found that sucrose intake after ovariectomy exacerbates visceral obesity and glucose intolerance, and that D-allulose effectively ameliorates these metabolic abnormalities. GLP-1-stimulating dietary components such as D-allulose may represent a safe and promising preventive strategy for metabolic dysfunction associated with menopause.

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Iba, K., Kyo, M., Ishihara, H., Nagao, A., Kawabe, M., Ohbayashi, K., Yada, T., Iwasaki, Y.. 2026-01-07. Exacerbation of sucrose-induced visceral obesity and glucose intolerance by ovariectomy and its GLP-1-dependent amelioration by the rare sugar D-allulose. https://doi.org/10.64898/2026.01.06.697863

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