Clinical trial NCT01209429: Importance of the GH/IGF-1 Axis for Human Substrate and Energy Metabolism During Calorie Restriction
Official title: Importance of the GH/IGF-1 Axis for Human Substrate and Energy Metabolism During Calorie Restriction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Calorie restriction
GH/IGF-I axis
STATb5
SIRT1
Intracellular signaling peptides and proteins
Fasting
Growth hormone
IGF-1
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2010-09-27
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: This study will investigate whether growth hormone is modulated by the enzyme SIRT1 and by that is stimulating lipolysis on expense of IGF-I production. This is done in 10 healthy men on calorie restriction on 4 study days with fat and skeletal muscle biopsies.

Detailed description: It has been shown that calorie restriction enhances the length of life in yeast, worms, fish and rodent. Whether this elongation of life due to calorie restriction can be applied to humans is not known. However, it is a fact that calorie restriction will decrease the risk of developing metabolic disturbances such as diabetes, hypertension and atherosclerosis.

On the molecular level the specific relations are not fully understood. This study will investigate the possible connection between SITR1 and the relation to the GH/IGF-I axis and STAT5b in healthy men. The participant will fast 42 and 12 hours respectively, and have GH or placebo infusions. The design is a classical 2x2 design and will be randomized.

Knowledge of the interactions between calorie restriction, SIRT1, STAT5b and the GH/IGF-I axis will apply important information about the relations between aging, energy metabolism and metabolic disturbances.

Eligibility criteria: Inclusion Criteria:

* healthy lean men
* age \>18

Exclusion Criteria:

* metabolic disturbances
* alcohol drug abuse
* malign disease: current or previous

Primary outcomes:
measure: Description of intracellular pathways to clarify the interplay between calorie restriction, SIRT1, STATb5, and the GH/IGF-I axis
timeFrame: 6 hour study days
Secondary outcomes:
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: University Hospital of Aarhus, Norrebrogade
Study officials:
affiliation: University Hospital of Aarhus
name: Jens Otto L Jørgensen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hjelholt AJ, Lee KY, Arlien-Soborg MC, Pedersen SB, Kopchick JJ, Puri V, Jessen N, Jorgensen JOL. Temporal patterns of lipolytic regulators in adipose tissue after acute growth hormone exposure in human subjects: A randomized controlled crossover trial. Mol Metab. 2019 Nov;29:65-75. doi: 10.1016/j.molmet.2019.08.013. Epub 2019 Aug 20.
citation: Nellemann B, Vendelbo MH, Nielsen TS, Bak AM, Hogild M, Pedersen SB, Bienso RS, Pilegaard H, Moller N, Jessen N, Jorgensen JO. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity. Acta Physiol (Oxf). 2014 Feb;210(2):392-402. doi: 10.1111/apha.12183. Epub 2013 Nov 22.