Figure 1.

Hyperphagia causes mature-onset obesity in p62^−/− mice. A, Weight change (mean ± SD; n = 5) and (B) food intake (mean ± SD; n = 5) of p62^−/− (red), p62^+/− (green), and control p62^+/+ (wild-type, blue) male mice fed a standard diet ad libitum. C, Daily oxygen consumption rates of body weight-matched wild-type (blue, 30.3 ± 2.8 g) and p62^−/− (red, 29.8 ± 1.6 g) mice (13–16-weeks-old; mean ± SD; n = 6). D, Pair-feeding experiment. Pellets were provided at 3.0 ± 0.1 g/mouse/d. A 3.0 g portion of food was given to each mouse in a separate cage at 18:00, and the body weight (mean ± SD; n = 5) was measured every week. E, F, Computed tomography (CT) analysis of the visceral fat content. Restricted daily food intake (3.0 g/d/mouse) for 10 weeks from the age of 5–15 weeks (Fig. 1D) suppressed visceral fat accumulation compared with that under ad libitum-feeding conditions in the p62^−/− mice. The amount of visceral fat (F) was calculated from CT data. G, Glucose tolerance tests in ad libitum fed (left, 25–28-weeks-old) or diet restricted for 10 weeks (right, 20-weeks-old) wild-type and p62^−/− mice. Blood glucose levels after intraperitoneal injection of glucose (1 g/kg body weight) are shown. All data in F and G represent the mean (n = 5–6) ± SD. Asterisks represent statistical significance; ***p < 0.001, *p < 0.05.