Federal Project Grant Award Summary

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded Stanford University a Project Grant of $796,068 (effective February 1, 2026 through January 31, 2031) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to conduct fundamental biochemical and physiological research on the beta-hydroxybutyrate (BHB) shunt metabolic pathway. The research aims to elucidate the mechanisms by which this newly discovered third pathway of BHB metabolism—distinct from established ketogenesis and ketone oxidation pathways—contributes to energy balance and ketosis-associated weight loss. The project will generate conditional knockout mouse models with selective ablation of the BHB shunt in specific cell types (liver, macrophages, and gut) and investigate the molecular mechanisms by which downstream BHB-amino acid metabolites regulate feeding behavior through interaction with body weight-associated ion channels.

This research deliverable addresses a critical gap in metabolic disease understanding by potentially reshaping the scientific understanding of ketone body biochemistry and identifying novel therapeutic targets for metabolic disorders including obesity and diabetes. The work is positioned to generate novel biological insights, transgenic research tools, and mechanistic data that could inform future therapeutic development strategies targeting ketone metabolism in metabolic disease treatment and prevention.