GLP-1 Release by Rare Sugar D-Allulose Ameliorates Sucrose-Induced Obesity and Glucose Intolerance in Ovariectomized Mice

TL;DR

D-allulose, a rare sugar, helps reduce obesity and glucose issues in mice lacking estrogen, possibly through GLP-1.

Contribution

D-allulose improves metabolic dysfunction in ovariectomized mice via GLP-1, offering a safer alternative to hormone therapy.

Findings

D-allulose reduced visceral fat and improved insulin resistance in sucrose-fed ovariectomized mice.

GLP-1 receptor knockout mice showed reduced benefits from D-allulose, confirming GLP-1's role.

Sucrose intake worsened obesity and glucose intolerance in ovariectomized mice.

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 secretion of glucagon-like peptide-1 (GLP-1), a gut hormone, and 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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