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Effect of Acute Bout of Exercise on Levels of PAHSA

Not Applicable
Recruiting
Conditions
Insulin Sensitivity
Interventions
Other: Exercise
Other: Fasting control
Registration Number
NCT05572905
Lead Sponsor
Lenka Rossmeislova
Brief Summary

Exercise represents an important tool in the prevention and treatment of metabolic disorders associated with obesity and aging, such as type 2 diabetes and cardiovascular disease. Besides skeletal muscle and its myokinins, the metabolic effects of exercise also rely on the induction of favorable changes in adipose tissue function. For example, adipose tissue is a source of lipokinins from the family of palmitic acid esters of hydroxy fatty acids (PAHSA), which have anti-inflammatory and insulin-sensitizing properties. We have recently shown that 4 months of exercise training increases PAHSA levels in adipose tissue and circulation. However, the mechanisms involved in the induction of PAHSA levels in response to exercise are unknown. The aim of the Effect of Acute Bout of Exercise on Levels of PAHSA (ETAPA) project is therefore to investigate the regulation of PAHSA metabolism in response to both acute and chronic exercise. To achieve this goal, we will employ state-of-the-art analytical methods to measure PAHSA levels in both adipose tissue and circulation of subjects of various ages and adiposity status. The main output of the ETAPA project will be the proof of principle regarding the important role of PAHSA lipokinins in exercise-induced enhancement of insulin sensitivity and the identification of potential drug targets that could be used to further improve PAHSA metabolism for the treatment of metabolic disorders associated with aging or obesity.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
75
Inclusion Criteria
  • healthy young lean, young obese and elderly omnivorous men and women as defined by BMI, self-reported activity, self-reported medical history and self-reported diet assessment
  • must be able to withstand repeated blood draws
  • must be able to undergo abdominal fat biopsy
Exclusion Criteria
  • use of betablockers
  • use of glucocorticoids
  • use of non-steroidal anti-inflammatory drugs
  • use of metformin in prediabetes
  • use of psychiatric drugs such as selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, anticonvulsants and others
  • oncologic malignancy
  • chronic inflammatory or autoimmune diseases
  • diabetes mellitus
  • chronic ischemic heart disease
  • cardiovascular and pulmonary disease
  • renal and hepatological disease as assessed per biochemistry
  • musculo-skeletal deviations limiting physical performance
  • substance abuse
  • other than omnivorous diet

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Young obese men and womenFasting control25 to 40 y.o. participants with body mass index in range of 30 to 45.
Young obese men and womenExercise25 to 40 y.o. participants with body mass index in range of 30 to 45.
Young lean men and womenExercise25 to 40 y.o. participants with body mass index in range of 18.5 to 25
Young lean men and womenFasting control25 to 40 y.o. participants with body mass index in range of 18.5 to 25
Elderly men and womenExercise65 to 80 y.o. participants with body mass index in range of 18.5 to 30.
Elderly men and womenFasting control65 to 80 y.o. participants with body mass index in range of 18.5 to 30.
Primary Outcome Measures
NameTimeMethod
Assessment of PAHSA levels and its changes in response to exercise and fasting in cohorts differing in age and fat mass2 years

PAHSA levels \[nmol/l\] in serum sampled at pre-set time-points during control and intervention visits (including exercise session or plain fasting) and in subcutaneous abdominal white adipose tissue will be assessed by quantitative targeted lipidomic analysis.

Absolute and fold-change of PAHSA in plasma induced by experimental intervention (exercise, fasting) will be compared among individual cohorts.

Secondary Outcome Measures
NameTimeMethod
Correlation of PAHSA levels with anthropometry and clinical characteristics2 years

Basal levels of PAHSA and its changes in response to interventions will be correlated with anthropometric parameters (age, weight, fat mass) and parameters of physical fitness. Fat mass will be assessed by dual energy X-ray absorptiometry. Intercohort matching of obese and elderly subjects based on fat mass will be improved throughout the recruitment phase by utilization of fat mass assessment on two distinct certified bioimpedance instruments. Cohort physical fitness will be calculated as average from individual VO2max values obtained from maximum ergometry testing. Intercohort matching of young lean and young obese men and women will be based on age.

Correlation of PAHSA with various indexes of insulin sensitivity2 years

Basal levels of PAHSA and its changes in response to interventions will be correlated with indices of muscle insulin sensitivity (MISI), hepatic insulin resistance (HIRI), adipose tissue insulin resistance (Adipo-IR) and homeostatic model assessment of insulin resistance (HOMA-IR). Values for measurement will be obtained by biochemical analysis of blood sampled during 5-point oral glucose tolerance test.

Trial Locations

Locations (1)

3rd faculty of medicine, Charles University

🇨🇿

Prague, Czechia

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