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; P<0.001) and fat percentage (3.5%; P<0.001) but did not affect
glucose uptake nor lipolysis. The hypercaloric diet increased adipose tissue microvascular recruitment (P=0.041) and decreased the ratio between skeletal muscle and adipose tissue microvascular blood volume during
hyperinsulinemia (P=0.019).
Insulin-induced vasodilation of isolated skeletal muscle arterioles was significantly lower in participants compared with controls (P<0.001). The hypocaloric diet reversed all of these changes, except the increase in adipose tissue microvascular recruitment.
CONCLUSIONS: 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.