The Role of Lactate in Lipolysis and Catabolism in Humans

Study Overview
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Brief Summary
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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: Intravenous sodium D/L-lactate 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.

Official Title
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The Role of Lactate in Lipolysis and Catabolism in Humans

Conditions
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Hyperlactatemia, Healthy, Lactate

Intervention / Treatment
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* Drug: Na-lactate
* Drug: Sodium chloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Na-lactate<br>Iv infusion of sodium D/L lactate | Drug: Na-lactate<br>* intravenous<br>* Other names: Sodium lactate;|
| Placebo Comparator: Sodium chloride<br>Iv infusion of Sodium chloride | Drug: Sodium chloride<br>* Intravenous<br>* Other names: NaCl;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lipolysis, Catabolism, Glucose metabolism, Aminoacid metabolisme