Deficient Mc4r signaling–driven obesity accelerates thymic involution. The WT and Mc4r knockout mice were maintained on an ad libitum chow diet and aged for 8 months. (A) The real-time PCR analysis of Mc4r mRNA in 2- to 3-month-old C57BL/6 mice (n = 3). The total RNA from cells and tissues was DNAse digested, and RT-PCR analysis shows the CNS-restricted expression of Mc4r. (B) Obesity mediated by Mc4r deficiency causes thymic adiposity. Thymus is highlighted in blue box and arrows, compared with control WT mice; inset shows malformed fatty thymus in Mc4r^−/− animals. (C-D) Compared with WT mice, loss of Mc4r significantly (P < .05) reduces the frequency of CD4 and CD8 naive (CD62L⁺CD44⁻) T cells (top left quadrant) and (E) decreases sjTREC numbers in splenic CD4 cells. (F,H) Mc4r deficiency–driven obesity significantly reduces the ETP (Lin^loCD44⁺ckit^hi) cells in thymus and (G-H) LSK cells in BM (n = 5 per group; top right quadrant).