LEPR and type 2 diabetes mellitus: To explore the effect of 3HB on T2D, leptin receptor deficiency mice (db/db) and streptozotocin (STZ) induced T2D mice were used.16 1,3-butanediol (1,3-BDO), a precursor of endogenous 3HB, could be efficiently converted to 3HB in the liver.17,18 Considering the effect of increasing blood 3HB concentration and the influence on fluid intake volume of mice, 10% 1,3-BDO aqueous solution was chosen as drinking fluid for the mice to maintain a blood 3HB level of over 1.5 mM based on the literatures and corresponding experimental results (Supplementary Fig. S5b).19,20