Figure 4.

Loss of neuronal Cadm1 protects from diet and genetically-induced obesity and insulin resistance. (a) Body weight curves of Slc17a6-Cre, Cadm1^flox/flox mice (n=10) and littermate controls (n=6) on high fat diet (HFD). (b) Glucose measurements during an ITT from 16-week old Slc17a6-Cre, Cadm1^flox/flox mice (n=7) and control littermates (n=10) after 10 weeks on HFD. (c) Energy expenditure from individual animals plotted against lean body mass in 16-week old Slc17a6-Cre, Cadm1^flox/flox mice (n=9) and littermate controls (n=10) after 10 weeks on HFD. (d) Energy expenditure from individual animals plotted against locomotor activity in 16-week old Slc17a6-Cre, Cadm1^flox/flox mice (n=9) and littermate controls (n=10) after 10 weeks on HFD. (e) Western blot analysis of Cadm1 and Cadm2 in total and synaptosome-enriched lysates from hypothalamus of 12-week-old Slc17a6-Cre, Cadm1^flox/flox crossed onto the Lep^ob/ob background (ob/MUT) mice and Lep^ob/ob littermates. (f) Body weight curves of ob/MUT mice (n=5) and Lep^ob/ob littermate controls (n=9) from 4-12 weeks of age. (g) Random glucose and plasma insulin measurements in ob/MUT mice (n=4) and Lep^ob/ob littermate controls (n=8). (h) Glucose measurements during an ITT on 12-week old ob/MUT mice (n=5) and control Lep^ob/ob littermates (n=9). (i) qRT-PCR analysis of G6pc and Pck1 expression in liver of 12-week old ob/MUT mice (n=4) and control Lep^ob/ob littermates (n=4). (j) Quantification of pancreatic β-cell mass (βCM) in ob/MUT mice (n=3) and littermate Lep^ob/ob controls (n=4) from 12 weeks of age. Immunohistochemistry of representative pancreatic sections from wild-type (WT), Lep^ob/ob and ob/MUT mice after detection of insulin (green). (k) Energy expenditure from individual animals plotted against lean body mass in 12-week old ob/MUT mice (n=5) and Lep^ob/ob littermates (n=6). (l) Quantification of food intake measured in 12-week old ob/MUT mice (n=5) and littermate Lep^ob/ob controls. (n=6). All results are presented as mean ± s.e.m. *P<0.05 and **P<0.01. Boxplots show median, lower and upper quartiles (box), and minimum and maximum (whiskers). Statistical analyses are described in the Methods and Supplementary Table 3.