Cadm2-deficient mice are protected from genetic obesity. A, Western blot analysis of Cadm1 and Cadm2 in total and synaptosome-enriched lysates from hypothalamus of 12-week-old Lepob/ob mice and Cadm2/ob. B, Body weight in male Cadm2/ob mice (n = 8), Lepob/ob mice (n = 13) and littermate controls (WT, n = 19) from 4 to 16 weeks of age. C, Random and fasting glucose measurements in 16-week-old Cadm2/ob mice, Lepob/ob mice and littermate controls (n = 3–7). D, Plasma insulin measurements in 16-week-old Cadm2/ob mice, Lepob/ob mice and littermate controls (n = 3–6). E, Glucose measurements during an insulin tolerance test on 12-week old Cadm2/ob mice, Lepob/ob mice and littermate controls (n = 4–6). F, Glucose measurements during a glucose tolerance test on 11-week old Cadm2/ob mice, Lepob/ob mice and littermate controls (n = 4–6). G, Glucose measurements during pyruvate tolerance test on 12-week old Cadm2/ob mice, Lepob/ob mice and littermate controls (n = 4–6). H-K, Quantification of O2 consumption, CO2 production, RER, and locomotor activity in 12-week old Cadm2/ob mice and Lepob/ob mice (n = 6–8). L, Body composition analysis of male Cadm2/ob mice and Lepob/ob mice (n = 6–9). M, Energy expenditure of individual animals plotted against lean body mass from 12-week old Cadm2/ob mice (n = 6) and Lepob/ob mice (n = 8). N, Energy expenditure of individual animals plotted against locomotor activity from 12-week old Cadm2/ob mice (n = 6) and Lepob/ob mice (n = 8). O, Quantification of daily food intake of Cadm2/ob mice (n = 6) and Lepob/ob mice (n = 8). P, Western blot analysis of STAT3 phosphorylation in the hypothalamus of Cadm2/ob mice and Lepob/ob mice after leptin injection (0.75 μg/g body weight). p-STAT3, phosphorylated STAT3. Q, Body weight in male Cadm2 mice and littermate controls (WT) from 5 to 20 weeks of age (n = 6–9). High fat diet feeding was initiated on 4 weeks old. R, Glucose measurements during an insulin tolerance test on 21-week old Cadm2 mice and littermate controls (n = 6–9). High fat diet feeding was initiated on 4 weeks-old. S, Glucose measurements during a glucose tolerance test on 22-week old Cadm2 mice and littermate controls (n = 6–9). High fat diet feeding was initiated on 4 weeks-old. Results are presented as mean ± SEM. *P < 0.05, **P < 0.01 and ***P < 0.001.