Figure 3.

Physiological analyses of wild-type and Gdf3^−/− mice. A, Caloric intake in 6-wk-old mice. Intake of high-fat diet was identical between wild-type and Gdf3^−/− mice, but Gdf3^−/− mice ate more regular diet (n = 8). B, Fat composition analysis of individual stool (left) and small intestine (right) samples from 12-wk-old mice fed high-fat diet. wt, Wild type; KO, knockout for Gdf3; MDG, mono- and diglycerides; C, cholesterol; FFA, free fatty acids; TG, triglycerides; ME, methyl ester; CE, cholesterol ester. C, Glucose tolerance tests in 12-wk-old mice on regular and high-fat diet (left), and 12- to 14-month-old mice on high-fat diet (right). Error bars were not included for mice fed regular diet to improve visibility of data from the high-fat diet cohorts. For the 12-wk-old mice, note that wild-type mice under high-fat diet conditions were delayed in returning to normal glucose levels 60 min after the glucose challenge. The glucose levels of Gdf3^−/− mice at this time point, irrespective of diet, were similar to those of the regular diet-fed wild-type mice (n = 6–8 for each group). In the older cohort, Gdf3^−/− mice are protected from diet-induced glucose intolerance (n = 5–7 for each group). D, Serum levels of leptin, PAI-1, and resistin in wild-type (closed circles) and Gdf3^−/− (open circles) mice on high-fat diet. PAI-1 levels were significantly lower in Gdf3^−/− mice (P = 0.001; n = 5–6). E, Representative 24-h indirect calorimetry tracings for 12-wk-old mice fed regular diet (left) and high-fat diet (right). Horizontal bar under graphs depicts light phase (white) or dark phase (black). Vertical gray arrow indicates removal of food; mice were considered fasted after 4 h. F, Summary of basal metabolic rates in 12-wk-old mice. Oxygen consumption values were collected from fasted mice during the light (quiescent) phase. Increased rates were recorded for the Gdf3^−/− mice irrespective of diet and were significantly different on high-fat diet. An asterisk (*) indicates a statistically significant difference (P < 0.05; n = 6–7) for each group. G, Summary of ambulatory activity for 6-wk-old high-fat diet-fed mice. The data was averaged from the last two full days of measurements. Fine activity levels also showed no significant difference between the genotypes (n = 6). H, Cold tolerance tests in 16-wk-old mice. Heavier Gdf3^−/− mice were picked that had similar weights as the wild-type mice that were used in this study (n = 3–4). HFD, High-fat diet; reg, regular.