Additionally, studies performed in vivo indicate that α adrenergic agonists inhibit the release of peripheral 5-HT from ECs [41]. It is well known that during obesity, peripheral 5-HT is increased [46] and blunts the thermogenesis by negatively regulating the sensitivity of adipose tissues to β-adrenergic stimulation [47] that is known to stimulate peroxisome proliferator-activated receptors gamma (PPARg) and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α), which are master regulators of uncoupling protein 1 (UCP1)-mediated thermogenesis [48,49]. Here, PPARG is linked to obesity due to melanocortin 4 receptor deficiency.