Tanycytic G6PT silencing prevents obesity induced by early postnatal overnutrition.

Tanycytes are ependymal glial cells that express the glucose-6-phosphate transporter (G6PT), which facilitates the incorporation of phosphorylated glucose from the cytosol into the reticular lumen. Herein, we show the antiobesogenic effects of G6PT-expressing tanycytes in a murine model of early postnatal overnutrition. Obesity in adult mice was induced by reducing litter size (SL mice) during the lactation period, a method that promotes excessive early nutrient intake. G6PT levels in tanycytes were analyzed using confocal-spectral microscopy. Tanycyte-specific G6pt silencing was carried out through the intracerebroventricular administration of AAV1-shG6pt-mCherry. Four weeks posttransduction, body weight, white adipose tissue weight, glucose metabolism and food intake were evaluated. We observed that SL mice exhibited reduced G6PT expression in tanycytes compared to mice with a normal phenotype. Remarkably, tanycyte-specific G6pt silencing in SL mice led to a significant reduction in body weight, accompanied by decreased adiposity. Furthermore, this intervention lowered blood glucose levels—restoring normoglycemia—and diminished food intake in response to fasting. These findings suggest that G6PT-expressing tanycytes may contribute to protective role against metabolic dysregulation. Targeting G6PT in tanycytes could help support the management and control of metabolic diseases.