CLOCK and obesity due to melanocortin 4 receptor deficiency: Mechanistically, obesity causes a reduction in PPAR-γ, which provokes downregulation of SLC1A5 (a direct target of PPAR-γ and a dual uptake transporter of glutamine and methionine) and reductions in adipocyte glutamine and methionine (two epigenetic activators of Bmal1), contributing to disruption of Bmal1 and other clock genes and thus to impaired adipocyte clock.