Molecular Mechanisms Underpinning Sarcopenic Obesity

Study Overview
=================
Brief Summary
-----------------
The coexistence of obesity and sarcopenia results in sarcopenic obesity, a high-risk geriatric condition associated with metabolic perturbations and several co-morbidities. Despite the rising numbers of older adults diagnosed with sarcopenic obesity, few studies have characterized this condition on the muscle cell and systemic level. This study sought to comprehensively assess the influence of sarcopenic obesity on muscle and blood-related parameters and compare it to non-sarocopenic obese and non-sarcopenic lean older adults.

Official Title
-----------------
Molecular Mechanisms Underpinning Sarcopenic Obesity

Conditions
-----------------
Sarcopenic Obesity, Obesity, Sarcopenia, Aging

Intervention / Treatment
-----------------
* Dietary Supplement: Essential amino acids (EAA)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body fat % in accordance with previously defined criteria Free of smoking (since 10 years) Able to walk without assistance Able to perform bilateral leg extension exercise Exclusion Criteria: History of or present disease of myocardial, vascular, endocrine, hepatic, renal, pulmonary or neuromuscular origin Uncontrolled hypo/hypertension Use of anticoagulants (Warfarin, Trombyl) Use of metformin or other anti-diabetic medications Poor appetite and unexplained weight loss (4,5 kg) over the past 6 months Active malignancy Present infection Dementia or delirium Other conditions that may interfere with the study protocol in the opinion of the PI

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sarcopenic obesity<br>Age: 70-80 years Men, ALM/W < 25.7 %, body fat % > 35 Women, ALM/W < 19.7 %, body fat % > 40 | Dietary Supplement: Essential amino acids (EAA)<br>* intake of 240 mg EAA per kg lean body mass after a resistance exercise session<br>|
| Non-sarcopenic obese<br>Age: 70-80 years Men, ALM/W > 25.7 %, body fat % > 35 Women, ALM/W > 19.7 %, body fat % > 40 | Dietary Supplement: Essential amino acids (EAA)<br>* intake of 240 mg EAA per kg lean body mass after a resistance exercise session<br>|
| Non-sarcopenic lean<br>Age: 70-80 years Men, ALM > 7.0 kg/m2, body fat % < 25 Women, ALM > 5.5 kg/m2, body fat % < 32 | Dietary Supplement: Essential amino acids (EAA)<br>* intake of 240 mg EAA per kg lean body mass after a resistance exercise session<br>|
| Young lean<br>Age: 18-40 years Men, ALM > 7.0 kg/m2, body fat % < 25 Women, ALM > 5.5 kg/m2, body fat % < 32 | Dietary Supplement: Essential amino acids (EAA)<br>* intake of 240 mg EAA per kg lean body mass after a resistance exercise session<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fiber type-specific cell signalling | This measure will be investigated during an experimental trial in which the participants are subjected to an acute bout of resistance exercise followed by the ingestion of essential amino acids (240 mg/kg lean mass). During this 3 hour time period, the participants will donate two muscle biopsies, one before exercise and the second one 1 hour after exercise. Cell signalling networks related to muscle mass regulation will be examined in these biopsy samples. The signal will be measured using Western blotting and the signal obtained is expressed in relation to baseline (adjusted volume intensity). | 1 hour after ingestion of essential amino acids and resistance exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle fiber characteristics | Fiber type-specific area measured using immunofluorescence microscope in muscle biopsies collected at baseline (prior to ingestion of essential amino acids and resistance exercise). Unit of measurement is square micrometers (µm^2). | 1 hour prior to ingestion of essential amino acids and resistance exercise | 
| Whole body muscle volume | Indices of muscle volume and fat infiltration obtained with magnetic resonance imaging (MRI). Unit of measurement is cubic centrimeters (cm^3). | 1 hour | 
| Whole body glucose tolerance | Oral glucose tolerance test in which the participants will ingest a standardized glucose drink and blood glucose levels will be monitored throughout a period of 2 hours. Unit of measurement is mmol/L glucose. | 2 hours | 
| Accelerometer-assessed physical activity levels | Hip-worn accelerometer data (Actigraph GT3X) collected over 7 consecutive days. Unit of measurement is steps per day. | 1 week | 
| Isometric and isokinetic leg muscle strength | Muscle performance will be evaluated at a single timepoint during the study using IsoMed2000 dynamometer. Participants will perform a maximal isometric contraction at 60 degrees of knee flexion. Unit of measurement is Newton meter (N-m). | 1 hour |