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CUTTING SUGAR PREFERENCE FROM THE GUT
Emily Alway
*1,2, Alam Coss
2, Carlos Puerto
2, Laila Khan-Farooqi
2, Melanie M. Kaelberer
2,1, Diego V. Bohórquez
2,11Duke University Department of Neurobiology, Durham, NC; 2Duke University Department of Medicine, Durham, NC
While bariatric surgery effectively treats obesity and diabetes, a deeper understanding of its mechanisms is crucial for developing less invasive therapies that can replicate its benefits. One intriguing clue lies in the consistent observation that bariatric surgery alters food preferences, particularly decreasing the desire for sweet foods. This change coincides with altered expression of intestinal sodium-glucose transporters (SGLTs), which play a key role in sugar sensing. Our previous work identified specialized intestinal cells called neuropod cells, and the SGLTs they express, as critical drivers of sugar preference.
Hypothesis: We propose that bariatric surgery alters sugar sensing by neuropod cells, leading to decreased sugar preference and contributing to the observed metabolic improvements.
Methods: To test this hypothesis, we developed a refined mouse model of vertical sleeve gastrectomy (VSG) with high post-operative survival (70%) and significant weight loss. Using the IntelliCage, a social housing system that allows for continuous monitoring of food choices, we assessed preferences for sugar, sweetener, protein, and fat before and after VSG. We then used qPCR to analyze SGLT1 transcript expression in neuropod cells and generated a novel mouse line lacking SGLT1 specifically in these cells to determine the functional impact on sugar preference.
Results: VSG, but not sham surgery, led to a decrease in preference for caloric sucrose, accompanied by a reduction in SGLT1 transcript expression specifically within the neuropod cells of the duodenum. Importantly, mice lacking SGLT1 in their neuropod cells displayed a reduced preference for moderate sucrose concentrations, mirroring the shift observed after VSG.
Conclusions: These findings reveal a critical role for neuropod cells in regulating sugar preference and suggest that modulating their activity may offer a novel, non-surgical avenue for treating obesity and diabetes.
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