The Role of Lactate in Lipolysis and Catabolism in Humans

Not Applicable

Completed

• Conditions: Healthy; Hyperlactatemia; Lactate
• Interventions: Drug: Sodium chloride; Drug: Na-lactate

• Registration Number: NCT04710875
• Lead Sponsor: University of Aarhus

Brief Summary

Lactate may have anti-lipolytic effects when plasma concentrations of lactate reach levels similar to those seen during high intensity exercise.

This study aims to investigate how lactate concentrations similar to those achieved during high intensity exercise affects lipolysis in humans. In addition to this, to investigate how increased lactate concentrations affects glucose- and amino acid metabolism.

8 healthy males will be included. Study participants will undergo two separate investigation days that will be identical except for the interventions:

1. Intravenous sodium D/L-lactate

2. Intravenous sodium chloride.

The study consists of a 3-hour basal period followed by a 3-hour hyperinsulinemic euglycemic clamp. During the study we will:

* Estimate insulin sensitivity during the hyperinsulinemic euglycemic clamp (M value)

* Use tracer kinetics to estimate lipid-, glucose and amino acid metabolism using \[9,10-3H\]-palmitate, \[3-3H\]-glucose, \[15N\]-phenylalanine, \[15N\]-tyrosine, \[2H4\]-tyrosine and \[13C\]-Urea.

* Do muscle- and adipose tissue biopsies for analyses of signaling pathways involved in regulation of lipid-, glucose and amino acid metabolism.

* Do blood samples of relevant hormones, metabolites and cytokines.

* Use indirect calorimetry to estimate study participants' resting energy expenditure and respiratory quotient during the basal period.

* Estimate cardiac ejection fraction by echocardiography and measure blood pressure during both the basal- and clamp period.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-09
• Study First Submitted: 2020-12-01
• Study First Submitted QC: 2021-01-12
• Study First Posted: 2021-01-15
• Study Start: 2021-03-10
• Primary Completion: 2021-06-29
• Study Completion: 2021-06-29
• Last Update Submitted: 2022-01-21
• Last Update Posted: 2022-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

Inclusion Criteria

• male
• >18 years of age
• BMI >19 and below 30
• Written and verbal consent to participation

Exclusion Criteria

• Chronic illness
• daily use of medicine
• affected blood samples at screening, as assessed by the PI
• does not speak and understand Danish
• Assessed unsuitable by PI.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sodium chloride	Sodium chloride	Iv infusion of Sodium chloride
Na-lactate	Na-lactate	Iv infusion of sodium D/L lactate

Primary Outcome Measures

Name	Time	Method
Acute Metabolic effects of Na-lactate compared with NaCl on lipolysis	2 hours (1 hour basal period, 1 hour clamp)	Change in \[9,10-3H\]-palmitate tracer flux

Secondary Outcome Measures

Name	Time	Method
Acute Metabolic effects of Na-lactate compared with NaCl on glucose metabolism	6 hours (3 hours basal period, 3 hours clamp)	Change in glucose metabolism quantified with \[3-3H\]-glucose tracer
Indirect calorimetry during clamp	20 minutes	Change in estimation of resting energy expenditure during clamp. Difference between interventions.
Blood samples - Insulin	6 hours.	Insulin concentrations. Difference between interventions.
Insulin sensitivity	3 hours.	Hyperinsulinaemic euglycaemic clamp with 0.6mU/kg/min insulin and 20% glucose to calculate M value. Difference between interventions.
Acute metabolic effects of Na-lactate compared with NaCl on aminoacid metabolism	6 hours	Change in aminoacid metabolism quantified with \[15N\]-phenylalanine, \[15N\]tyrosine, \[2H4\]tyrosine and \[13C\]-Urea tracers.
Indirect calorimetry during basal conditions	20 minutes	Change in estimation of respiratory quotient during basal period. Difference between interventions.
Echocardiography	15 minutes	Change in cardiac ejection fraction during clamp period. Difference between interventions.
blood pressure	2 x 10 min	blood pressure (systolic and diastolic) during basal- and clamp
Blood samples - cortisol	6 hours.	cortisol concentrations. Difference between interventions.
Blood samples - GDF-15	6 hours.	GDF-15 concentrations. Difference between interventions.
Blood samples - glucagon	6 hours.	glucagon concentrations. Difference between interventions.
Blood samples - glucose	6 hours.	glucose concentrations. Difference between interventions.
Blood samples - c-peptid	6 hours.	c-peptid concentrations. Difference between interventions.
Blood samples - Ghrelin	6 hours.	Ghrelin concentrations. Difference between interventions.
Blood samples - free fatte acids	6 hours.	Free fatte acids concentrations. Difference between interventions.
Blood samples - lactate	6 hours.	lactate concentrations. Difference between interventions.
Changes in signaling in muscle tissue between interventions	After 3 and 5 hours of intervention	Western blot examinations of muscle tissue biopsies
Changes in signaling in adipose tissue between interventions	After 3 and 5 hours of intervention	Western blot examinations of adipose tissue biopsies

Trial Locations

Locations (2)

Medical/Steno Aarhus research laboratory; 🇩🇰 Aarhus, Central Region Denmark, Denmark

Aarhus University Hospital; 🇩🇰 Aarhus N, Denmark