Biology subjects

Korhonen, T.-M.

Publications and source records attributed to Korhonen, T.-M..

5 recordsLinked to original sources

bioRxiv2025

Loss of ovarian hormones modulates the nucleic acid content of circulating extracellular vesicles and skeletal muscle metabolism in response to acute exercise

Loss of ovarian hormones (i.e., menopause) leads to negative effects on metabolic health. While exercise offers significant benefits, it seems to be insufficient to completely reverse these changes. The mechanisms by which exercise conveys the effects throughout the body are still poorly understood. Extracellular vesicles (EVs) are released into circulation during exercise. EVs carry small non-coding RNAs (sRNAs), such as microRNAs (miRs), which are proposed as mediators of the effects of exercise. We have previously shown that the miR response to acute exercise of EVs and HDL is diminished in postmenopausal women with low estrogen levels, which we were able to replicate here also in a rat model. In this study, we examined the effect of loss of ovarian hormones and acute exercise in the sRNA cargo of EV and HDL particles in female rats. We show for the first time that loss of ovarian hormones affects specifically the nucleic acid cargo of circulating EVs. We further show that the estrogen responsive miRs regulate anaerobic glycolytic pathway in skeletal muscle. Finally, we demonstrate that the loss of ovarian hormones leads to higher anaerobic energy production during an acute bout of exercise, implicating an inferior ability to sustain aerobic energy production during exercise.

physiology↗

bioRxiv2024

Menopause-associated proteomic and lipidomic alterations in high-density lipoprotein: Perimenopause is characterized by smaller triacylglycerols-enriched particles.

High-density lipoprotein particles (HDL) possess anti-inflammatory, anti-thrombotic, cytoprotective, and anti-oxidative properties, thus protecting against cardiovascular diseases. Menopause is associated with changes in serum metabolome and HDL size distribution. We analyzed the protein and lipid composition of the HDL particles from pre-, peri-, and postmenopausal women (N=216) with nuclear magnetic resonance and mass spectrometry to get a deeper insight into the composition of HDL in different stages of menopause. Both particle size and composition differed; in perimenopause, the proportion of small HDL particles (8.7 nm on average) was higher, and the proportion of large HDL particles (12.1 nm on average) was lower than in pre- or postmenopause. In perimenopause, each particle size class was enriched with triacylglycerols, and the calculated lipid class ratio of triacylglycerol/cholesteryl ester was the highest within perimenopausal HDL particles. This potentially affects the HDL interaction with lipid-modifying enzymes. We also observed directionally opposite associations for HDL cholesteryl ester and unesterified cholesterol with systemic estradiol and follicle-stimulating hormone levels, especially regarding S-sized HDL particles, but not the hormone associations with HDL triacylglycerols. Perimenopausal HDL also exhibited a lower proportion of apolipoproteins (apoA-I, apoA-II, apoC-I, apoC-III, apoD and apoE) per particle than premenopausal or postmenopausal HDL. In summary, we found that premenopausal and postmenopausal HDL particles were compositionally similar and differed from perimenopausal ones. We suggest that menopause, and especially the unbalanced hormonal state in perimenopause, are reflected in the lipid and protein compositions of the HDL, which, in turn, may affect the functions of the HDL particle.

molecular biology↗

bioRxiv2023

Menopausal transition alters female skeletal muscle transcriptome

Menopause is associated with unfavorable changes in body composition. Skeletal muscle cells are targets of hormonal regulation and are affected by the interplay between coding and non-coding RNAs. Muscle transcriptome, including messenger-RNA (mRNA), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) has not previously been studied in women during the menopausal transition. Thus, we took a multi-RNA omics approach to get insight into transcriptome-wide events of menopause. Our study included baseline and follow-up muscle samples from seven early (EarlyMT) and 17 late perimenopausal (LateMT) women transitioning to early postmenopause during the study. Total RNA was sequenced and differential expression (DE) of the transcriptome was investigated. The potential gene functions were investigated with pathway analyses and protein level expression with Western Blot. We found 30 DE mRNA genes in EarlyMT and 19 in LateMT participating in pathways controlling cell death, growth, and interactions with external environment. Lack of protein level changes may indicate a specific role of the regulatory RNAs during menopause. Ten DE lncRNA transcripts were identified but did not result in DE lncRNAs genes. No DE miRNAs were found. Despite the lack of DE findings in regulatory RNAs, we identified putative regulatory networks, likely to be affected by estradiol availability. The changes in gene expression were correlated with observed changes in body composition variables, indicating muscularity and adiposity regulators to be affected by menopausal transition. In essence, the observed DE genes and their regulatory networks may offer novel mechanistic insights on factors affecting body composition during and after menopause.

molecular biology↗

bioRxiv2022

Systemic circulating microRNA landscape in Lynch syndrome

MicroRNAs (miRs) are non-coding RNA-molecules that regulate gene expression. Global circulating miR (c-miR) expression patterns (c-miRnome) change with carcinogenesis in various sporadic cancers. Therefore, aberrantly expressed c-miRs could have diagnostic, predictive and prognostic potential in molecular profiling of cancers. c-miR functions in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), also known as Lynch syndrome (LS), have remained understudied. LS cohort provides an ideal population for biomarker mining due to increased lifelong cancer risk and excessive cancer occurrence. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers. Our discovery cohort included 81 healthy path_MMR carriers and 37 non-LS controls. Our analysis also included cancer cohort comprised of 13 path_MMR carriers with varying cancers and 24 sporadic rectal cancer patients. We showed for the first time that c-miRnome can discern healthy path_MMR carriers from non-LS controls but does not distinguish healthy path_MMR carriers from cancer patients with or without path_MMR. Our c-miR expression analysis combined with in silico tools suggest ongoing alterations of biological pathways shared in LS and sporadic carcinogenesis. We observed that these alterations can produce a c-miR signature which can be used to track oncogenic stress in cancer-free path_MMR carriers. Thus, c-miRs hold potential in monitoring which cancer patients would require more intensive surveillance or clinical management. SignificanceC-miRnome can discern between healthy persons with or without path_MMR but does not distinguish healthy path_MMR carriers from cancer patients with or without path_MMR, indicating an ongoing alteration of biological pathways that can be used to track oncogenic stress at cancer-free state.

cancer biology↗

bioRxiv2022

Extracellular vesicles and high-density lipoproteins: Exercise and estrogen-responsive small RNA carriers

Decreased systemic estrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both estrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signaling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that estrogen deficiency caused by menopause blunts acute exercise-induced systemic miR-response in both EV and HDL particles. HIGHLIGHTSO_LIExtracellular vesicles and HDL particles have a distinct sRNA content C_LIO_LIExtracellular vesicles and HDL particles carry both host and nonhost sRNA cargo C_LIO_LIEstrogen deficiency blunts the c-miR-response induced by acute exercise C_LIO_LIExercise responsive miRs in HT users may regulate the choice of energy substrate C_LI

molecular biology↗