Effect of Acute Bout of Exercise on Levels of PAHSA

Insulin Sensitivity Clinical Trial

— ETAPA  

Official title:

Novel Approaches to Enhance Insulin-sensitizing Effects of Exercise: Targeting PAHSA Metabolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05572905
• Other study ID #: NU21-01-00469
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2022
• Source: Charles University, Czech Republic
• Contact: Lenka Rossmeislová, PhD
• Phone: +420 26710 2211
• Email: lenka.rossmeislova[@]lf3.cuni.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity

Intervention

Other:
• Exercise
Patients after overnight fast will cycle on ergo-meter for 60 minutes. No per-oral food intake will be allowed during the test. Level of the intensity of exercise will be determined as individual range of heart frequency (HF), oxygen consumption (VO2) and respiratory quotient (RQ) just bellow the aerobic threshold of the given participant (close to anticipated fatmax). These values will be obtained during maximal capacity stress test on cyclo-ergo-meter. This maximum stress test will be performed at least one week prior to the 60 minutes exercise to eliminate potential carry-over effect. Power output will be modulated during the 60 minutes of exercise to ensure keeping participants values of HF, RQ and VO2 in the given range. Blood will be sampled at 5 time points with interval of 30 minutes during the exercise (0, 30, 60, 90, 120) and 24 hours post-exercise.
• Fasting control
The same participants will be monitored while resting for 120 minutes in calm environment. No peroral food intake will be allowed during the test. Fasting control will take place at least one week apart of the exercise. Blood will be sampled at 5 timepoints with interval of 30 minutes during the exercise (0, 30, 60, 90, 120) and 24 hours post-control.

Locations

Country	Name	City	State
Czechia	3rd faculty of medicine, Charles University	Prague

Sponsors (3)

Lead Sponsor	Collaborator
Lenka Rossmeislova	Czech Academy of Sciences, Faculty Hospital Kralovske Vinohrady

Country where clinical trial is conducted

Czechia, 

References & Publications (2)

Brezinova M, Kuda O, Hansikova J, Rombaldova M, Balas L, Bardova K, Durand T, Rossmeisl M, Cerna M, Stranak Z, Kopecky J. Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers. Biochim Biophys Acta Mo — View Citation

Paluchova V, Oseeva M, Brezinova M, Cajka T, Bardova K, Adamcova K, Zacek P, Brejchova K, Balas L, Chodounska H, Kudova E, Schreiber R, Zechner R, Durand T, Rossmeisl M, Abumrad NA, Kopecky J, Kuda O. Lipokine 5-PAHSA Is Regulated by Adipose Triglyceride — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of PAHSA levels and its changes in response to exercise and fasting in cohorts differing in age and fat mass	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.	2 years
Secondary	Correlation of PAHSA levels with anthropometry and clinical characteristics	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.	2 years
Secondary	Correlation of PAHSA with various indexes of insulin sensitivity	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.	2 years

External Links

•   Webpage for future participants in Czech language.