From the Department of Internal Medicine (A.L.E., R.I.M., J.W., D.H.v.R., M.D., M.H.H.K., E.H.S.), Amsterdam UMC, location VU University Medical Center, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Department of Endocrinology and Metabolism, Amsterdam UMC, location Academic Medical Center, Amsterdam, The Netherlands (M.J.S.).
Arterioscler Thromb Vasc Biol. 2020 Jul;40(7):1695-1704. doi: 10.1161/ATVBAHA.120.314129. Epub 2020 May 14.
In mice fed a high-fat diet, impairment of insulin signaling in endothelium is an early phenomenon that precedes decreased insulin sensitivity of skeletal muscle, adipose tissue, and liver. We assessed in humans whether short-term overfeeding affects insulin-induced microvascular recruitment in skeletal muscle and adipose tissue before changes occur in glucose uptake and lipolysis. Approach and Results: Fifteen healthy males underwent a hypercaloric and subsequent hypocaloric diet intervention. Before, during, and after the hypercaloric diet, and upon return to baseline weight, all participants underwent (1) a hyperinsulinemic-euglycemic clamp to determine insulin-induced glucose uptake and suppression of lipolysis (2) contrast-enhanced ultrasonography to measure insulin-induced microvascular recruitment in skeletal muscle and adipose tissue. In addition, we assessed insulin-induced vasodilation of isolated skeletal muscle resistance arteries by pressure myography after the hypercaloric diet in study participants and controls (n=5). The hypercaloric diet increased body weight (3.5 kg; <0.001) and fat percentage (3.5%; <0.001) but did not affect glucose uptake nor lipolysis. The hypercaloric diet increased adipose tissue microvascular recruitment (=0.041) and decreased the ratio between skeletal muscle and adipose tissue microvascular blood volume during hyperinsulinemia (=0.019). Insulin-induced vasodilation of isolated skeletal muscle arterioles was significantly lower in participants compared with controls (<0.001). The hypocaloric diet reversed all of these changes, except the increase in adipose tissue microvascular recruitment.
In lean men, short-term overfeeding reduces insulin-induced vasodilation of skeletal muscle resistance arteries and shifts the distribution of tissue perfusion during hyperinsulinemia from skeletal muscle to adipose tissue without affecting glucose uptake and lipolysis. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02628301.
在高脂饮食喂养的小鼠中，内皮细胞胰岛素信号转导受损是一个早期现象，先于骨骼肌、脂肪组织和肝脏的胰岛素敏感性降低。我们在人体中评估了短期过度喂养是否会影响骨骼肌和脂肪组织中胰岛素诱导的微血管募集，而葡萄糖摄取和脂肪分解没有变化。
15 名健康男性接受了高热量和随后低热量饮食干预。在高热量饮食之前、期间和之后，以及在恢复到基线体重时，所有参与者都接受了（1）高胰岛素-正常血糖钳夹以确定胰岛素诱导的葡萄糖摄取和脂肪分解抑制，（2）对比增强超声检查以测量胰岛素诱导的骨骼肌和脂肪组织中的微血管募集。此外，我们在研究参与者和对照组（n=5）中评估了高热量饮食后通过压力测微技术测量胰岛素诱导的孤立骨骼肌阻力动脉血管舒张。高热量饮食增加了体重（3.5 公斤；<0.001）和脂肪百分比（3.5%；<0.001），但不影响葡萄糖摄取和脂肪分解。高热量饮食增加了脂肪组织微血管募集（=0.041），并在高胰岛素血症期间降低了骨骼肌和脂肪组织微血管血容量之间的比值（=0.019）。与对照组相比，参与者的胰岛素诱导的孤立骨骼肌小动脉血管舒张明显降低（<0.001）。低热量饮食逆转了所有这些变化，除了脂肪组织微血管募集的增加。
在瘦人中，短期过度喂养会降低骨骼肌阻力动脉的胰岛素诱导血管舒张，并在高胰岛素血症期间将组织灌注的分布从骨骼肌转移到脂肪组织，而不影响葡萄糖摄取和脂肪分解。
