Accordingly, in contrast to the HFD, where endothelial function in the TA was resistant to early HFD-induced dysfunction, in S961-treated mice it was not the case, pointing out to profound effects of altered insulin signaling in both types of PVAT depots, even in the absence of fat overload and obesity after as short-term treatment as 2 weeks with S961. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.