Effects of Free Fatty Acids and 3-hydroxybutyrate on Protein, Glucose, Lipid Metabolism and Intracellular Signals.

Effects of Free Fatty Acids and 3-hydroxybutyrate on Protein, Glucose, Lipid Metabolism and Intracellular Signals; a Study on Muscle Wasting and Metabolism During Acute Inflammation and Potential Anabolic Mechanisms.

The investigators hypothesize that the investigators can detect protein-sparing effects of administration of the ketone 3-hydroxybutyrate and free fatty acids during simulation of an acute inflammatory disease. The investigators use the infusion of endotoxin, US standard reference E.coli in healthy subjects as a model for inflammation / infection and to evaluate the effect on protein metabolism using different tracers and the investigators can measure the various intracellular signaling pathways of selected muscle and adipose tissue.

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome
• Intervention / Treatment: Other: Endotoxin, US standard reference E.coli

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Medical Research Laboratory, Department of Internal Medicine and Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 20 < body mass index < 30 kg/m2.
• written and orally informed consent before enrollment.

Exclusion Criteria:

• participation in other studies using radioactive tracers or other exposure to radiation (X-rays, scintigraphy etc).
• allergy to soy products or eggs
• diabetes, any type
• epilepsy
• ongoing infection
• immune deficiency
• cardiovascular disease
• dysregulated hypertension
• primary muscles disease, congenital or acquired

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (isotonic saline); Endotoxin + isotonic saline. Reference for model of acute inflammatory illness	Other: Endotoxin, US standard reference E.coli
Experimental: Acipimox + Placebo (isotonic saline); Endotoxin + Acipimox + Placebo (isotonic saline). Intervention: blockage of endogenous lipolysis.	Other: Endotoxin, US standard reference E.coli
Experimental: Acipimox + free fatty acids; Endotoxin + Acipimox + free fatty acids. Intervention: free fatty acids	Other: Endotoxin, US standard reference E.coli
Experimental: Acipimox + 3-hydroxybutyrate; Endotoxin + Acipimox + 3-hydroxybutyrate. Intervention: 3-hydroxybutyrate	Other: Endotoxin, US standard reference E.coli

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protein metabolism	Measurements of protein oxidation during intervention using radioactive tracer techniques.	6 hours intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activated intracellular signalling pathways	Measurements on biopsies from muscle and fatty tissue taken on day of study	study day

Other Outcome Measures

Outcome Measure	Time Frame
Other systemic metabolic effects	6 hours of intervention

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Niels Møller, Professor, Institute of Clinical Medicine, Aarhus University, Denmark. Department of Internal Medicin and Endocrinology, Aarhus university hospital, Aarhus, Denmark.

Publications and helpful links

General Publications

• Thomsen HH, Rittig N, Johannsen M, Moller AB, Jorgensen JO, Jessen N, Moller N. Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS-induced inflammation in humans: anticatabolic impact of ketone bodies. Am J Clin Nutr. 2018 Oct 1;108(4):857-867. doi: 10.1093/ajcn/nqy170.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (Estimate): December 19, 2012

Study Record Updates

• Last Update Posted (Estimate): November 25, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: fever; sepsis; cytokine release
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Shock; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 11422796; 1-10-72-530-12 (Other Identifier: Regional Ethics Comite)