Biology subjects

Cajka, T.

Publications and source records attributed to Cajka, T..

5 recordsLinked to original sources

bioRxiv2026

Higher baseline levels of fatty acid esters of hydroxy fatty acids do not further enhance the stimulatory effect of regular exercise on insulin sensitivity in obese mice

BackgroundExercise is an effective way to improve metabolic health, and the modulation of adipose tissue (AT) secretory functions may play a significant role in this process. AT produces various lipokines, including fatty acid esters of hydroxy fatty acids (FAHFA), which increase insulin sensitivity and have anti-inflammatory effects. While factors such as sex, age, obesity, and genetics influence FAHFA levels, their impact on exercise-induced FAHFA regulation remains unclear. MethodsFirst, sex-specific responses to an acute bout of exercise were assessed in wild-type (WT) and ADTRP-deficient (ADTRP KO) mice. Fasted mice underwent acute treadmill exercise until exhaustion, followed by analysis of non-esterified fatty acids in plasma, ex vivo lipolysis in the presence or absence of a hormone-sensitive lipase (HSL) inhibitor, and FAHFA release from AT (measured by LC-MS). Second, obese male WT and ADTRP KO mice fed a high-fat diet underwent 7 weeks of regular treadmill exercise (5 days/week), after which parameters of glucose homeostasis, plasma and AT FAHFA levels, and AT lipid profiles were analyzed. ResultsAcute exercise-induced increases in plasma non-esterified fatty acid levels, AT lipolysis, and FAHFA release from AT explants were more pronounced in male mice of both genotypes. Conversely, pharmacological inhibition of HSL using BAY 59-9435 increased FAHFA release from AT explants only in females. In obese sedentary ADTRP KO mice, insulin sensitivity was improved compared with their WT counterparts. Although regular exercise suppressed weight gain in obese animals of both genotypes, insulin sensitivity improved only in WT mice. Chronic exercise generally had no effect on plasma FAHFA levels in mice fed ad libitum; however, in WT mice, it increased the levels of FAHFA-containing triacylglycerol estolides, which were associated with improved insulin sensitivity. ConclusionsAcute exercise revealed sex-specific differences in AT lipolysis and FAHFA metabolism, with HSL playing an important role in FAHFA hydrolysis. Chronic exercise in obesity increases insulin sensitivity and FAHFA storage in AT; however, this effect is absent in ADTRP KO mice, which exhibit elevated FAHFA levels in AT, a condition associated with improved insulin sensitivity even in non-exercising animals.

physiology↗

bioRxiv2025

Sequestration of the polyunsaturated fatty acids protects the cells with oxidative phosphorylation deficiency from ferroptosis

Impaired energy production is a hallmark of mitochondrial oxidative phosphorylation (OXPHOS) defects. However, secondary metabolic disturbances also represent an important trigger for pathologies originating from OXPHOS aberrations. We identified that cells with OXPHOS deficiencies accumulate triacylglycerols enriched in polyunsaturated fatty acids (PUFAs), which are stored in lipid droplets. Sequestration of PUFAs is a critical component of a broader stress response, which also includes downregulation of cellular desaturases and upregulation of glutathione peroxidase 4 (GPX4). Here, we demonstrate that this mechanism represents a physiologically relevant protective strategy, manifesting in the cells under hypoxia and fibroblasts derived from patients with primary mitochondrial complex IV deficiency. As proof of principle, we observed elevated PUFA-enriched triacylglycerols in the plasma of patients with Myoclonic Epilepsy with Ragged Red Fibres (MERRF). Our findings reveal a novel protective mechanism against ferroptosis, which preserves membrane integrity when mitochondrial respiration is compromised. HighlightsO_LIOXPHOS-deficient cells trigger polyunsaturated fatty acid (PUFA) stress response that includes sequestration of PUFAs to TGs, downregulation of desaturases, and upregulation of lipid peroxide detoxification C_LIO_LIPUFA trafficking to TGs stored in lipid droplets protects the cells against lipid peroxidation and ferroptosis C_LIO_LIOXPHOS-deficient cells synthesise fatty acids de novo from glutamine-derived acetyl-CoA when reductive carboxylation is permissible C_LIO_LIPUFA stress response is activated in patients with mitochondrial deficiencies and during hypoxia C_LI

cell biology↗

bioRxiv2023

Physiological variability in mitochondrial rRNA predisposes to metabolic syndrome

Metabolic syndrome is a growing concern in developed societies, and due to its polygenic nature, the genetic component is only slowly being elucidated. Common mitochondrial DNA sequence variants have been associated with symptoms of metabolic syndrome and may be relevant players in the genetics of metabolic syndrome. We investigate the effect of mitochondrial sequence variation on the metabolic phenotype in conplastic rat strains with identical nuclear but unique mitochondrial genomes, challenged by high-fat diet. We find that the variation in mitochondrial rRNA sequence represents a risk factor in insulin resistance development, which is caused by diacylglycerols accumulation induced by tissue-specific reduction of the oxidative capacity. These metabolic perturbations stem from the 12S rRNA sequence variation affecting mitochondrial ribosome assembly and translation. Our work demonstrates that physiological variation in mitochondrial rRNA might represent a relevant underlying factor in the progression of metabolic syndrome. Competing interestsThe authors declare that no competing interests exist.

physiology↗

bioRxiv2020

MS-DIAL 4: accelerating lipidomics using an MS/MS, CCS, and retention time atlas

To the EditorWe formulated mass spectral fragmentations of lipids across 117 lipid subclasses and included ion mobility tandem mass spectrometry (MS/MS) to provide a comprehensive lipidome atlas with retention time, collision cross section, and MS/MS information. The all-in-one solution from import of raw MS data to export of a common output format (mztab-M) was packaged in MS-DIAL 4 (http://prime.psc.riken.jp/) providing an enhanced standardized untargeted lipidomics procedure following lipidomics standards initiative (LSI) semi-quantitative definitions and shorthand notation system of lipid structures with a 1-2% estimated false discovery rate, which will contribute to harmonizing lipidomics data across laboratories to accelerate lipids research.

bioinformatics↗

bioRxiv2019

The circulating lipidome is largely defined by sex descriptors in the GOLDN, GeneBank and the ADNI studies

Biological sex is one of the major anthropometric factors which influences physiology, metabolism and health status. We have investigated the effect of sexual dimorphism on the blood lipidome profile in three large population level studies - the Alzheimers disease neuroimaging initiative - ADNI (n =806), the GeneBank Functional Cardio-Metabolomics cohort (n= 1015) and the Genetics of Lipid lowering Drugs and Diet Network - GOLDN (n=422). In total, 355 unique lipids from 15 lipid classes were detected across all three studies using LC-MS. Sixty percent of these lipids differed between men and women in all three cohorts, and up to 87% of all lipids demonstrated sex differences in at least one cohort. ChemRICH enrichment statistics on lipid classes showed that phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, ceramides, sphingomyelins and cholesterol esters were found at higher levels in female subjects while triacylglycerols and lysophosphatidylcholines were found at higher levels in male participants across the three cohorts. This strong sex effect on the blood lipidome suggests that specific regulatory mechanisms may exist that regulate lipid metabolism in a different manner between men and women. Cohort studies involving blood lipidomics should consider separate analyses for male and female participants instead of combined analyses treating sex as a confounding factor.

biochemistry↗