Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

High-fat overfeeding impairs peripheral glucose metabolism and muscle microvascular eNOS Ser1177 phosphorylation

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Growth and Adult Height in Girls With Turner Syndrome Following IGF-1 Titrated Growth Hormone Treatment

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Changes in the homeostatic appetite system after weight loss reflect a normalization toward a lower body weight

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Evaluation of Serum Insulin-like Factor 3 Quantification by LC-MS/MS as a Biomarker of Leydig Cell Function

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genetic variation at PPP1R3B increases hepatic CT attenuation and interacts with prandial status on plasma glucose

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Heterozygous Mutation (Q459R) in the Calcium-Sensing Receptor Gene Causes Familial Hypocalciuric Hypercalcemia 1 (FHH1)

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects with Hepatic Steatosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Impaired lipolysis in propionic acidemia: A new metabolic myopathy?

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Effects of protein intake prior to carbohydrate-restricted endurance exercise: a randomized crossover trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Siôn A Parry
  • Mark C Turner
  • Rachel M Woods
  • Lewis J James
  • Richard A Ferguson
  • Matthew Cocks
  • Katie L Whytock
  • Juliette A Strauss
  • Sam O Shepherd
  • Anton J M Wagenmakers
  • Gerrit van Hall
  • Carl J Hulston
View graph of relations

CONTEXT: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood.

OBJECTIVE: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation.

DESIGN: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS.

RESULTS: High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole-body glucose clearance (-16%; P = 0.021) and peripheral insulin sensitivity (-26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser1177 phosphorylation that was seen after carbohydrate plus protein ingestion.

CONCLUSION: High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser1177 phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume105
Issue number1
Pages (from-to)65-77
ISSN0021-972X
DOIs
Publication statusPublished - 1 Jan 2020

ID: 59937872