Enhanced thermogenesis in response to trehalose feeding is leptin-independent. (A) Heat production over time in mice (n = 8 mice per group) fed regular chow diet with either sterile water (black line) or 3% trehalose in water ad libitum (5 total days, purple line) and placed in indirect calorimeters for at least 24 h prior to death. (B) Quantification of dark cycle (left) and light cycle (right) thermogenesis in mice fed sterile water or 3% trehalose in water. (C-E) Oxygen consumption (C), CO2 production (D), and respiratory exchange ratio (RER) (E) in same mice presented in (A). (F-I) Quantification of oxygen consumption (F), CO2 production (G), heat generation (H), and RER (I) by indirect calorimetry in 8-wk-old leptin-deficient ob/ob mice fed with or without 3% trehalose water ad libitum (5 days); n = 5 per group. * and **** P < 0.05 and < 0.0001 respectively versus control by Student’s T-test.