Fig. 4: Aggrecan deposition is involved in the adaptive response to fasting.

a, b Ghrelin-induced cFos expression in the ventral and dorsal ARH of PBS^ARH and ADAMTS-5^ARH wildtype mice (b, PBS^ARH n = 6, ADAMTS-5^ARH n = 7, ARH analyzed bilaterally, ventral: two-tailed unpaired t test, *p = 0.0367, t(24) = 2.212; dorsal: two-tailed Mann–Whitney test, **p = 0.0085). c, d Immunolabeling for cFos (red) and counts of cFos-positive neurons in the ARH of PBS^ARH and ADAMTS-5^ARH mice fed ad libitum. 3-5mice, ARH analyzed bilaterally, means and s.e.m. indicated, two-tailed unpaired t test. e Number of cFos-positive neurons in the VMH of PBS^ARH and ADAMTS-5^ARH mice treated with ghrelin. 7 mice, ARH analyzed bilaterally, means and s.e.m. indicated, two-tailed unpaired t test. f, g Intravenous 3 kDa Texas red dextran diffusion in PBS^ARH and ADAMTS-5^ARH mice (3 mice, means and s.e.m. are shown, ARH analyzed bilaterally, one-way ANOVA test, *p = 0.01, F (2, 9) = 7.303). h, i Food intake (h) and refeeding (i) (h, in 30-min ghrelin-injected; 12–14 mice, means and s.e.m. are shown, two-tailed unpaired t test, **p = 0.004, t(25) = 3.192) and 16-h fasting (i, 7–14 mice, ∅ represents uninjected mice; means and s.e.m. are shown, Kruskal–Wallis test, ∅ versus ADAMTS-5^ARH *p = 0.039; PBS^ARH versus ADAMTS-5^ARH *p = 0.033) PBS^ARH, ADAMTS-5^ARH and wildtype mice. Dashed lines indicated the boundaries of the ARH considered for quantification. ME median eminence, ARH hypothalamic arcuate nucleus, VMH ventromedial nucleus of the hypothalamus. 3V: third ventricle. Scale bars: 50 μm except where indicated. Source data are provided as a Source Data file.