Effect of Acute Bout of Exercise on Levels of PAHSA

NCT05572905 | Completed

• 1 other identifier: NU21-01-00469
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Sensitivity

Keywords

acute exercise; adipose tissue; insulin sensitivity; PAHSA; lipokines; FAHFA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Correlation of PAHSA levels with anthropometry and clinical characteristics

  2 years

• Correlation of PAHSA with various indexes of insulin sensitivity

  2 years

Study Arms (3)

Young lean men and women

EXPERIMENTAL

25 to 40 y.o. participants with body mass index in range of 18.5 to 25

Other: Exercise; Other: Fasting control

Young obese men and women

EXPERIMENTAL

25 to 40 y.o. participants with body mass index in range of 30 to 45.

Other: Exercise; Other: Fasting control

Elderly men and women

EXPERIMENTAL

65 to 80 y.o. participants with body mass index in range of 18.5 to 30.

Other: Exercise; Other: Fasting control

Interventions

Exercise OTHER

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.

Elderly men and women; Young lean men and women; Young obese men and women

Fasting control OTHER

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.

Elderly men and women; Young lean men and women; Young obese men and women

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• healthy young lean, young obese and older 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lenka Rossmeislova: lead
• Faculty Hospital Kralovske Vinohrady: collaborator
• Czech Academy of Sciences: collaborator

Study Sites (1)

3rd faculty of medicine, Charles University

Prague, Prague, 10000, Czechia

Location

Related 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 Mol Cell Biol Lipids. 2018 Feb;1863(2):126-131. doi: 10.1016/j.bbalip.2017.11.004. Epub 2017 Nov 14.

  PMID: 29154942 RESULT

• 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 Lipase and Primes Adipocytes for De Novo Lipogenesis in Mice. Diabetes. 2020 Mar;69(3):300-312. doi: 10.2337/db19-0494. Epub 2019 Dec 5.

  PMID: 31806624 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Insulin Resistance

Interventions

Exercise

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Lenka Rossmeislová, PhD

  3rd Faculty of Medicine of Charles University in Prague

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Head of Laboratory of Physiology and Pathophysiology of Adipose Tissue, Department of Pathophysiology, Third Faculty of Medicine

Model Details: single groups assignment

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: October 10, 2022
• Study Start: May 1, 2021
• Primary Completion: December 12, 2025
• Study Completion: December 12, 2025
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)