Effects of a Hypercaloric and Hypocaloric Diet on Insulin-Induced Microvascular Recruitment, Glucose Uptake, and Lipolysis in Healthy Lean Men

Anna L. Emanuel*, Rick I. Meijer, Jorn Woerdeman, Daniel H. Van Raalte, Michaela Diamant, Mark H.H. Kramer, Mireille J. Serlie, Etto C. Eringa, Etto C. Eringa, Erik H. Serné

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: 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.

Original languageEnglish
Pages (from-to)1695-1704
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number7
Publication statusPublished - Jul 2020

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