Figure 4. FMO3 in obese/diabetic mice and humans.

(a–h) Eight- to ten–week-old male mice were killed in the non-fasted state. (a–d) Streptozotocin (STZ)-treated mice were compared with their vehicle-treated controls (Veh) and (e–h) ob/ob mice were compared with their wild-type controls (Con); all mice were killed in the non-fasted state. (i–m) Six-week-old male ob/ob mice were treated with control (Con) or FMO3 ASO for 4 weeks and were killed in the non-fasted state. Hepatic gene expression (b,c,f,g,i,k,l) was measured using real-time PCR, and protein levels (d,h,j) were measured by western blotting whole-cell lysates. Glucose tolerance testing (m) was performed after 3 weeks of ASO treatment. Data represent the mean and s.e.m.; n=5–8; *P<0.05 (Student's t-test) vehicle versus STZ treated (a to d), control versus ob/ob mice (e to h), control ASO-treated ob/ob mice versus FMO3 ASO-treated ob/ob mice (i to m). (n–o) Two- to three-month-old male and female Flox and LIRKO mice were killed in the non-fasted state. Hepatic gene expression (n) was measured using real-time PCR, and protein levels (o) were measured by western blotting whole-cell lysates. (p–s) Four- to six-week-old female Flox and LIRKO mice were treated with control (Con) or FMO3 ASO for 7 weeks and killed in the non-fasted state. Hepatic gene expression (p,r) was measured by real-time PCR, and protein levels were measured by western blotting whole-cell lysates (q). Glucose tolerance testing (s) was performed after 3 weeks of ASO treatment. Data represent the mean and s.e.m.; n=5; *P<0.05 (Student's t-test) Flox versus LIRKO mice with control ASO treatment; ^#P<0.05 (Student's t-test) control versus FMO3 ASO-treated mice of the same genotype (blue # is for Flox mice and red # is for LIRKO mice). (t,u) Liver biopsies were taken from age and sex-matched patients undergoing bariatric surgery (Obese) or other abdominal surgeries (Controls), and FMO3 expression was measured by real-time PCR (u); biochemical and physiological data from these patients are shown (t). Data represent the mean and s.e.m., as described in Methods. P values were determined by the Mann–Whitney test for continuous variables and by the χ² test for categorical variables (t) or the Student's t-test (u).