PPARG and obesity due to melanocortin 4 receptor deficiency: Mechanistically, PPAR-γ, downregulated in obesity, provokes changes in a cascade of events in the adipocytes, including decreased expression of the uptake transporter SLC1A5, reductions in glutamine and methionine uptake, lower production of acetyl-CoA and S-adenosylmethionine (SAM), and reduced histone acetylation and methylation, thereby repressing Bmal1 transcription and expression.