KETO-SENSE is a clinical research study investigating how ketone bodies affect energy metabolism and insulin sensitivity in humans. Ketone bodies are naturally produced by the liver during fasting or prolonged exercise and can serve as an alternative fuel for the brain, heart, and muscles. In this study, ten overweight but otherwise healthy adults aged 55-70 years will participate in four study days at Aarhus University Hospital. Participants will receive one of four interventions in a randomized crossover design: 1) growth hormone (GH) and a ketone supplement, 2) GH and placebo, 3) a saline infusion with the ketone supplement, or 4) placebo (saline infusion and placebo supplement). The study uses advanced PET/CT imaging, indirect calorimetry, and tissue biopsies to measure how ketones influence fat breakdown, glucose uptake, and energy expenditure. By understanding these mechanisms, the study aims to clarify whether oral ketone supplementation can improve insulin sensitivity and energy metabolism - findings that could be relevant for common conditions such as overweight, insulin resistance, and type 2 diabetes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
10
Continuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) for approximately 7 hours to induce physiological lipolysis.
Oral administration of D-β-hydroxybutyrate ester (R-1,3-butanediol β-hydroxybutyrate).
Continuous IV infusion of isotonic saline as placebo for growth hormone.
Oral administration of an isocaloric placebo drink.
Aarhus University Hospital
Aarhus N, Denmark
RECRUITINGInsulin-stimulated glucose uptake in skeletal muscle and organs measured by [¹⁸F]-FDG PET
Quantification of insulin-stimulated glucose uptake rates in skeletal muscle and selected organs using dynamic \[¹⁸F\]-FDG PET during a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity.
Time frame: During four experimental study days conducted over approximately 12 weeks
Tissue-specific uptake of β-hydroxybutyrate and palmitate measured by PET/CT imaging
Quantification of tissue-specific uptake of β-hydroxybutyrate (BHB) and palmitate in skeletal muscle, adipose tissue, and myocardium using dynamic PET/CT imaging with \[¹¹C\]-OHB and \[¹¹C\]-palmitate tracers.
Time frame: During four experimental study days conducted over approximately 12 weeks
Tissue-specific oxidation of β-hydroxybutyrate and palmitate measured by PET/CT imaging
Quantification of oxidation rates of β-hydroxybutyrate (BHB) and palmitate in skeletal muscle, adipose tissue, and myocardium using dynamic PET/CT imaging with \[¹¹C\]-OHB and \[¹¹C\]-palmitate tracers to assess tissue-specific substrate utilization.
Time frame: During four experimental study days conducted over approximately 12 weeks
Energy expenditure
Measurement of resting and insulin-stimulated energy expenditure using indirect calorimetry and analysis of respiratory exchange ratio (RER).
Time frame: During four experimental study days conducted over approximately 12 weeks
Cardiac output measured by PET/CT imaging
Quantification of cardiac output in the basal state and during the hyperinsulinemic-euglycemic clamp using dynamic PET/CT imaging to evaluate hemodynamic effects of GH and β-hydroxybutyrate.
Time frame: During four experimental study days conducted over approximately 12 weeks
Myocardial glucose and fatty acid uptake rates
Assessment of myocardial substrate metabolism using dynamic PET/CT imaging with \[¹⁸F\]-FDG and \[¹¹C\]-palmitate tracers during the basal period and the hyperinsulinemic-euglycemic clamp to quantify myocardial utilization of glucose and fatty acids.
Time frame: During four experimental study days conducted over approximately 12 weeks
Skeletal muscle pyruvate dehydrogenase (PDHa) enzymatic activity
Assessment of skeletal-muscle PDHa enzymatic activity determined from the rate of acetyl-CoA production using a radioactivity-based assay and normalized to creatine content in the muscle homogenate.
Time frame: During four experimental study days conducted over approximately 12 weeks
Adipose tissue lipoprotein lipase (LPL) enzymatic activity
Determination of heparin-releasable LPL activity in subcutaneous adipose-tissue and muscle biopsies using the glycerol-stabilized method to evaluate triglyceride-derived fatty-acid uptake.
Time frame: During four experimental study days conducted over approximately 12 weeks
Expression levels of lipolytic regulatory proteins in adipose tissue
Expression of regulators of lipolysis to assess GH- and BHB-mediated effects on lipid metabolism.
Time frame: During four experimental study days conducted over approximately 12 weeks
Phosphorylation levels of insulin-regulated proteins in skeletal muscle
Quantification of phosphorylation levels of insulin-regulated proteins in skeletal-muscle biopsies.
Time frame: During four experimental study days conducted over approximately 12 weeks
Expression levels of insulin-regulated proteins in skeletal muscle
Quantification of protein expression levels of insulin-regulated proteins in skeletal-muscle biopsies.
Time frame: During four experimental study days conducted over approximately 12 weeks
Expression levels of GH-regulated proteins (GHR, JAK2, STAT5, BCL6) in skeletal muscle and adipose tissue
Quantification of GH-regulated proteins (GHR, JAK2, STAT5, BCL6) in muscle and adipose biopsies using capillary electrophoresis immunoassay for each intervention condition.
Time frame: During four experimental study days conducted over approximately 12 weeks
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Relative mRNA expression of GH-responsive genes (SOCS1-3, CISH, IGF-I) in skeletal muscle and adipose tissue
Quantification of GH-responsive gene expression (SOCS1-3, CISH, IGF-I) in muscle and adipose biopsies using RT-PCR. Relative mRNA expression will be reported as fold change for each intervention condition.
Time frame: During four experimental study days conducted over approximately 12 weeks
Skeletal muscle mitochondrial oxidative phosphorylation capacity
Assessment of mitochondrial oxidative phosphorylation capacity in permeabilized muscle fibers obtained from vastus lateralis biopsies, measured by high-resolution respirometry (Oroboros Oxygraph-2k).
Time frame: During four experimental study days conducted over approximately 12 weeks
Muscle glycogen content
Measurement of skeletal-muscle glycogen stores to assess substrate utilization and glucose storage during growth-hormone and ketone interventions.
Time frame: During four experimental study days conducted over approximately 12 weeks