Clinical trial NCT05572905: Effect of Acute Bout of Exercise on Levels of PAHSA
Official title: Novel Approaches to Enhance Insulin-sensitizing Effects of Exercise: Targeting PAHSA Metabolism
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Insulin Sensitivity
Keywords: acute exercise
adipose tissue
insulin sensitivity
PAHSA
lipokinins
Lead sponsor: Charles University, Czech Republic
Sponsor class: OTHER
Collaborators: name: Faculty Hospital Kralovske Vinohrady
name: Czech Academy of Sciences
First posted: 2022-10-10
Enrollment: 75
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single groups assignment
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Assessment of PAHSA levels and its changes in response to exercise and fasting in cohorts differing in age and fat mass
timeFrame: 2 years
Secondary outcomes:
measure: Correlation of PAHSA levels with anthropometry and clinical characteristics
timeFrame: 2 years
measure: Correlation of PAHSA with various indexes of insulin sensitivity
timeFrame: 2 years
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: 3rd faculty of medicine, Charles University
Study officials:
affiliation: 3rd Faculty of Medicine of Charles University in Prague
name: Lenka Rossmeislová, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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 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.