Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans

Abstract

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 N 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.

Swine inflammation and necrosis syndrome is influenced by husbandry and quality of sow in suckling piglets, weaners and fattening pigs

“…The third hypothesis, that the clinical SINS score could be improved through improved husbandry (e.g., better supply of water and fibre), was also confirmed. This hypothesis is based on experience from working farms and published results on intestinal health: Microbiota dysbiosis and intestinal barrier impairment are associated with the development of a number of chronic inflammatory disorders and systemic diseases in humans (for a review, see [ 1 , 68 ]) and the pathogenic involvement of endotoxins has been reviewed [ 4 , 5 , 9 , 17 ]. Thanks to continuous monitoring by the herd health service of Baden-Wurttemberg, specific infectious intestinal diseases can be excluded.…”

Fasting and postprandial trimethylamine N ‐oxide in sedentary and endurance‐trained males following a short‐term high‐fat diet

“…The protocol was approved by the Virginia Polytechnic Institute and State University Institutional Review Board (#06-367) and both written and verbal informed consent were obtained from each participant. The present study was a secondary analysis that relied on stored blood samples collected from a study in which the experimental design and procedures have been described previously (Baugh et al, 2020;Bowser et al, 2020). Therefore, our sample size was limited to males in our previous study focused on skeletal muscle metabolism because in our experience females have declined to undergo the biopsy procedures (Baugh et al, 2020;Bowser et al, 2020).…”

“…The purpose of this investigation was to test the hypothesis that fasting and postprandial TMAO concentrations are reduced in endurance-trained males compared with sedentary males before and following a HFD. Our sample was limited to that included in the parent study which focused on skeletal muscle metabolism (Baugh et al, 2020;Bowser et al, 2020).…”

Postprandial skeletal muscle metabolism following a high-fat diet in sedentary and endurance-trained males

“…Seventeen metabolically healthy, SED (self-report of Ͻ2 h of physical activity per week for at least the last 3 mo and no planned, intentional exercise) and seven ET (self-report of running for Ն5 h per week and participating in Ն2 running races of Ն10 km in the last year) males without obesity and aged 18 -40 yr completed the study. Thirteen SED were participants in a prior study involving the same outcomes (10). Participants self-reported weight stability (Ϯ2.5 kg) for the prior 6 mo and had a body mass index between 18 and 30 kg/m 2 .…”

“…The relationship between a high-fat diet (HFD) and habitual physical activity behavior and their combined effect on skeletal muscle substrate metabolism is not well understood. Recently, we showed that metabolically healthy, SED individuals have an altered postprandial fat (10) and glucose oxidation (3,10) response to an HFD; however, whether substrate metabolism is modified by a HFD in endurance-trained (ET) individuals is not known. Therefore, the objective of the present study was to determine the influence of an HFD on fasting and postprandial skeletal muscle substrate metabolism in ET compared with SED males.…”