The initial increase in Ucp1 transcripts in response to HFD feeding in brown fat in rodents is followed by a decline at longer time points (23), thus raising a tempting speculation that the downregulation of Clstn3β in BAT of HFD-fed animals occurs prior to obesity-induced decline in Ucp1 transcripts. This evidence concerns the gene UCP1 and obesity due to melanocortin 4 receptor deficiency.