T. Shima (2026). Low-carbohydrate and high-protein diet may impair working memory via downregulation of hypothalamic T1R3 in mice. Nutrition and health, 32(2), 407-412. https://doi.org/10.1177/02601060251387805

PubMed 41124336

[Abstract]
BackgroundLow-carbohydrate, high-protein (LC-HP) diet declines working memory function in wild-type mice. Since the glucose sensor T1R3 is critical for cognitive function, it was unknown whether the LC-HP diet-induced memory declines involve altered brain T1R3 levels.AimTo examine the involvement of central T1R3 in LC-HP diet-induced memory declines.MethodsNine-week-old male C57BL/6J mice were assigned to either an LC-HP diet (25.1% carbohydrate, 57.2% protein, 17.7% fat) or a control diet (58.9% carbohydrate, 24.0% protein, 17.1% fat). Another set of standard-diet-fed mice received either hypothalamic T1r3 small interfering RNA (siRNA) or a negative control delivered via the osmotic pump. After four weeks, all mice underwent a Y-maze test, and T1r3 messenger RNA (mRNA) expression analysis in the hippocampus and hypothalamus.ResultsThe LC-HP diet declined working memory and hypothalamic T1r3 mRNA levels by about 27% (p < 0.01 and p < 0.05, respectively). Furthermore, hypothalamic T1r3-siRNA administration led to working memory deficits (p < 0.05).ConclusionHypothalamic T1R3 might be involved in LC-HP diet-induced working memory decline.