TY - JOUR
T1 - Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans
AU - Bowser, Suzanne M.
AU - McMillan, Ryan P.
AU - Boutagy, Nabil E.
AU - Tarpey, Michael D.
AU - Smithson, Andrew T.
AU - Osterberg, Kristin L.
AU - Neilson, Andrew P.
AU - Davy, Brenda M.
AU - Davy, Kevin P.
AU - Hulver, Matthew W.
N1 - Funding Information:
This work was supported by a Clinical Science and Epidemiology Award from the American Diabetes Association , ADA 1-13-CE-16 (Hulver).
Publisher Copyright:
© 2019 The Authors
PY - 2020/2
Y1 - 2020/2
N2 - Background: Our previous work demonstrated that a short-term high fat diet (HFD) increased fasting serum endotoxin, altered postprandial excursions of serum endotoxin, and led to metabolic and transcriptional responses in skeletal muscle in young, healthy male humans.Purpose: The purpose of the present study was to determine if a short-term high fat diet: 1) increases intestinal permeability and, in turn, fasting endotoxin concentrations and 2) decreases postprandial skeletal muscle fat oxidation.Methods: Thirteen normal weight young adult males (BMI 23.1 +/- 0.8 kg/m(2), age 22.2 +/- 0.4 years) were fed a control diet (55% carbohydrate, 30% fat, 9% of which was saturated, 15% protein) for two weeks, followed by 5 days of an isocaloric HFD (30% carbohydrate, 55% fat, 25% of which was saturated, 15% protein, isocaloric to the control diet). Intestinal permeability (via four sugar probe test) was assessed in the fasting state. Both before and after the HFD, a high fat meal challenge (HFM, 820 kcal, 25% carbohydrate, 63% fat, 26% of which was saturated, and 12% protein) was administered. After an overnight fast, blood samples were collected before and every hour for 4 h after the HFM to assess endotoxin, and other serum blood measures. Muscle biopsies were obtained from the vastus lateralis before and 4 h after the HFM in order to assess substrate oxidation (glucose, fatty acid and pyruvate) using radiolabeled techniques. Insulin sensitivity was assessed via intravenous glucose tolerance test. Intestinal permeability, blood samples and muscle biopsies were assessed in the same manner before and following the HFD.Main findings: Intestinal permeability was not affected by HFD (p > 0.05), but fasting endotoxin increased two fold following the HFD (p = 0.04). Glucose oxidation and fatty acid oxidation in skeletal muscle homogenates significantly increased after the HFM before the HFD (+97%, and +106% respectively) but declined after the HFM following 5 days of the HFD (-24% and +16% respectively). Fatty acid suppressibility of pyruvate oxidation increased significantly after the HFM (+32%) but this physiological effect was abolished following 5 days of the HFD (+7%). Insulin sensitivity did not change following the HFD.Conclusion: These findings demonstrate that in healthy young men, consuming an isocaloric HFD for 5 days increases fasting endotoxin, independent of changes in gut permeability. These changes in endotoxin are accompanied by a broad effect on skeletal muscle substrate metabolism including increases in postprandial fat oxidation. Importantly, the latter occurs independent of changes in body weight and whole-body insulin sensitivity. (C) 2019 The Authors. Published by Elsevier Inc.
AB - Background: Our previous work demonstrated that a short-term high fat diet (HFD) increased fasting serum endotoxin, altered postprandial excursions of serum endotoxin, and led to metabolic and transcriptional responses in skeletal muscle in young, healthy male humans.Purpose: The purpose of the present study was to determine if a short-term high fat diet: 1) increases intestinal permeability and, in turn, fasting endotoxin concentrations and 2) decreases postprandial skeletal muscle fat oxidation.Methods: Thirteen normal weight young adult males (BMI 23.1 +/- 0.8 kg/m(2), age 22.2 +/- 0.4 years) were fed a control diet (55% carbohydrate, 30% fat, 9% of which was saturated, 15% protein) for two weeks, followed by 5 days of an isocaloric HFD (30% carbohydrate, 55% fat, 25% of which was saturated, 15% protein, isocaloric to the control diet). Intestinal permeability (via four sugar probe test) was assessed in the fasting state. Both before and after the HFD, a high fat meal challenge (HFM, 820 kcal, 25% carbohydrate, 63% fat, 26% of which was saturated, and 12% protein) was administered. After an overnight fast, blood samples were collected before and every hour for 4 h after the HFM to assess endotoxin, and other serum blood measures. Muscle biopsies were obtained from the vastus lateralis before and 4 h after the HFM in order to assess substrate oxidation (glucose, fatty acid and pyruvate) using radiolabeled techniques. Insulin sensitivity was assessed via intravenous glucose tolerance test. Intestinal permeability, blood samples and muscle biopsies were assessed in the same manner before and following the HFD.Main findings: Intestinal permeability was not affected by HFD (p > 0.05), but fasting endotoxin increased two fold following the HFD (p = 0.04). Glucose oxidation and fatty acid oxidation in skeletal muscle homogenates significantly increased after the HFM before the HFD (+97%, and +106% respectively) but declined after the HFM following 5 days of the HFD (-24% and +16% respectively). Fatty acid suppressibility of pyruvate oxidation increased significantly after the HFM (+32%) but this physiological effect was abolished following 5 days of the HFD (+7%). Insulin sensitivity did not change following the HFD.Conclusion: These findings demonstrate that in healthy young men, consuming an isocaloric HFD for 5 days increases fasting endotoxin, independent of changes in gut permeability. These changes in endotoxin are accompanied by a broad effect on skeletal muscle substrate metabolism including increases in postprandial fat oxidation. Importantly, the latter occurs independent of changes in body weight and whole-body insulin sensitivity. (C) 2019 The Authors. Published by Elsevier Inc.
KW - Skeletal muscle
KW - Substrate oxidation
KW - Metabolic flexibility
KW - High fat diet
KW - Metabolic adaptation
KW - INTESTINAL PERMEABILITY
KW - INDUCED OBESITY
KW - ADIPOSE-TISSUE
KW - MICROBIOTA
KW - INFLAMMATION
KW - MICE
KW - SUPPLEMENTATION
KW - CHYLOMICRONS
KW - CARBOHYDRATE
KW - LIPOPROTEINS
U2 - 10.1016/j.metabol.2019.154041
DO - 10.1016/j.metabol.2019.154041
M3 - Article
C2 - 31785256
SN - 0026-0495
VL - 103
JO - Metabolism-Clinical and Experimental
JF - Metabolism-Clinical and Experimental
M1 - 154041
ER -