Adipocyte derived factor(s) is suppressed in the visceral fat in MC4R‐/‐ mice

Abstract

Adipocyte derived factors (ADFs) are suggested to contribute to endothelial dysfunction and cardiovascular diseases. We have shown that in ob/ob mice (ob), a model of obesity, both subcutaneous (SF) and visceral fats (VF) produce ADFs and induce vasodilation by activating KATP channels. There is evidence that MC4R‐/‐ mice, another model of obesity, do not develop hypertension or renal dysfunction despite the accumulation of VF. We hypothesize that there is be a decreased production of ADFs in MC4R‐/‐ mice. 12‐16 week old wild type (WT), ob, and MC4R‐/‐ were used. The spinotrapezius muscles in WT mice were prepared using intravital microscopy for observation of arcade arterioles. VF or SF in ob mice and MC4R‐/‐ was collected and were separately incubated in PSS. The vasodilatory responses to fat conditioned PSS were tested in WT mice before and after treatment with glibenclamide. The vasodilatory responses to SF or VF conditioned PSS from ob mice were not significantly different, similar with the vasodilation induced by SF conditioned PSS from MC4R‐/‐. However, VF from MC4R‐/‐ lead to a significantly attenuated vasodilation as compared with the SF‐induced dilation (31±6% vs. 69±7% n=4). Glibenclamide inhibited the vasodilations induced by each of the fat conditioned PSS. These results suggest that ADFs are suppressed in the VF in MC4R‐/‐ mice, which may be responsible for the protected outcomes despite of obesity.