Mechanisms of Estrogen Influence on Skeletal Muscle: Mass, Regeneration, and Mitochondrial Function

Sports Medicine, Journal Year: 2022, Volume and Issue: 52(12), P. 2853 - 2869

Published: July 30, 2022

Language: Английский

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Leveraging inter-individual transcriptional correlation structure to infer discrete signaling mechanisms across metabolic tissues

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 12, 2023

Inter-organ communication is a vital process to maintain physiologic homeostasis, and its dysregulation contributes many human diseases. Given that circulating bioactive factors are stable in serum, occur naturally, easily assayed from blood, they present obvious focal molecules for therapeutic intervention biomarker development. Recently, studies have shown secreted proteins mediating inter-tissue signaling could be identified by 'brute force' surveys of all genes within RNA-sequencing measures across tissues population. Expanding on this intuition, we reasoned parallel strategies used understand how individual mediate metabolic through correlative analyses gene variation between individuals. Thus, comparison quantitative levels expression relationships organs population aid understanding cross-organ signaling. Here, surveyed gene-gene correlation structure 18 310 individuals 7 103 diverse strains mice fed normal chow or high-fat/high-sucrose (HFHS) diet. Variation such as FGF21, ADIPOQ, GCG, IL6 showed enrichments which recapitulate experimental observations. Further, similar were applied explore both within-tissue mechanisms (liver PCSK9) encoding enzymes producing metabolites (adipose PNPLA2), where inter-individual aligned with known roles these critical pathways. Examination sex hormone receptor correlations highlighted the difference tissue-specific traits. We refer resource gene-derived (GD-CAT) tools data built into web portal enabling users perform without single line code (gdcat.org). This enables querying any tissue find correlated patterns genes, cell types, pathways, network architectures organs.

Language: Английский

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Dysregulated systemic metabolism in a Down syndrome mouse model

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 68, P. 101666 - 101666

Published: Dec. 29, 2022

Trisomy 21 is one of the most complex genetic perturbations compatible with postnatal survival. Dosage imbalance arising from triplication genes on human chromosome (Hsa21) affects multiple organ systems. Much Down syndrome (DS) research, however, has focused addressing how aneuploidy dysregulates CNS function leading to cognitive deficit. Although obesity, diabetes, and associated sequelae such as fatty liver dyslipidemia are well documented in DS population, only limited studies have been conducted determine gene dosage whole-body metabolism. Here, we conduct a comprehensive systematic analysis key metabolic parameters across different physiological states Ts65Dn trisomic mouse model DS. mice euploid littermates were subjected phenotyping under basal (chow-fed) state pathophysiological obesity induced by high-fat diet (HFD). RNA sequencing liver, skeletal muscle, two major fat depots impact tissue transcriptome. Pathway enrichments, gene-centrality, driver estimates performed provide insights into autonomous non-autonomous mechanisms contributing dysregulation systemic Under state, chow-fed both sexes had elevated locomotor activity energy expenditure, reduced fasting serum cholesterol levels, mild glucose intolerance. Sexually dimorphic deterioration homeostasis became apparent when challenged diet. While obese exhibited dyslipidemia, male also showed impaired insulin sensitivity, mitochondrial activity, fibrotic inflammatory signatures adipose tissue. Systems-level highlighted conserved pathways potential endocrine drivers adipose-liver crosstalk that contribute dysregulated lipid A combined alteration expression disomic peripheral tissues dysregulations mice. These data lay groundwork for understanding vivo

Language: Английский

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Identifying joint association between body fat distribution with high blood pressure among 7 ∼ 17 years using the BKMR model: findings from a cross-sectional study in China

BMC Public Health, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 2, 2025

To investigate the joint associations between various body fat distribution parameters and high blood pressure (HBP) using Bayesian Kernel Machine Regression (BKMR) model in school-aged children. A diverse sample of 7 ∼ 17 years old (N = 1423; 50.25% boys) was recruited for this study. Fat multiple parts, including trunk, legs, android region, gynoid region percentage were measured. HBP defined as either systolic or diastolic exceeded age-, sex- height-specific 95th percentiles. The chi-square test utilized to compare differences groups. BKMR employed analyze effects indicators on while accounting potential confounders. Weighted Quantile Sum (WQS) used characterize relative weights each parameter HBP. Additionally, stratified analyses performed by sexes overweight/non overweight prevalence 46.86% 35.10% obese (OB) boys girls, 17.96% 17.28% non-overweight (non-OB) respectively. Increased percentages android, parts are associated with a higher risk HBP, increased leg lower risk. Android contributed most OB (weight 0.34), girls 0.39), non-OB 0.56). Leg had significant protective effect (weight=-0.22) (weight=-0.44), (weight=-0.27). have inconsistent roles directions their association children different sex weight status. We recommend that statuses be provided body-part-specific exercise recommendations optimal chronic disease prevention control benefits.

Language: Английский

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One Month of Brief Weekly Magnetic Field Therapy Enhances the Anticancer Potential of Female Human Sera: Randomized Double-Blind Pilot Study

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 331 - 331

Published: Feb. 23, 2025

Preclinical studies have shown that the blood from female mice exposed weekly to magnetic fields inhibited breast cancer growth. This double-blind randomized controlled trial investigated whether analogous therapy could produce similar anticancer sera human subjects. Twenty-six healthy adult females (ages 30-45) were assigned either a group, receiving twice 1 mT exposures (10 min/session) for 4 weeks, or control who underwent identical sham exposure. Blood evaluated their capacity modulate cancer-related cellular responses and epithelial-mesenchymal transition. The group subjects exhibited significant effects strongest one month after last exposure, whereas unexposed males showed no effect. Female (n = 12) reduced cell proliferation (16.1%), migration (11.8%) invasion (28.2%) levels of key EMT markers relative 14). Magnetic modulated serum angiogenic myogenic biomarkers in manner consistent with improved management. Muscle-targeted holds potential enhance properties via an adaptive process, akin exercise training.

Language: Английский

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Red Meat Amino Acids for Beginners: A Narrative Review

Nutrients, Journal Year: 2025, Volume and Issue: 17(6), P. 939 - 939

Published: March 7, 2025

Meat is a major source of dietary protein and fat across the globe. Red white meat are terms consumers use to refer types meat; however, these do not fully encompass range nutrients provided by sources. refers from mammalian skeletal muscle, while poultry. both provide wide nutritional components in context fatty acids, amino acids micronutrients. Importantly, it has been demonstrated that acid profiles differ between red as well different sources meat. complete meaning contains all essential (EAAs), addition, non-essential (NEAAs). also most abundant bioavailable heme-iron for muscle growth cardiovascular health. indicated contributor rising incidence metabolic disorders even colorectal cancer. However, important note consumption linked conditions, typically overconsumption associated with obesity other symptoms. Similarly, preparation key factor its link cancer some methods produce carcinogens others not. Finally, may be situationally more beneficial groups than others, particularly cases sex aging. For pregnant women, increases increase intake semi-essential elderly, better preserve mass compared

Language: Английский

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Workshop Report—Heterogeneity and Successful Aging Part I: Heterogeneity in Aging—Challenges and Opportunities

The Journals of Gerontology Series A, Journal Year: 2025, Volume and Issue: 80(4)

Published: March 7, 2025

Historically, aging research has focused primarily on the study of differences in means varied measures obtained at different ages. However, growing evidence shown that for many parameters, variability measurements both between- and within-age groups increases with aging. Moreover, heterogeneity may become especially apparent when examined via longitudinal as opposed to cross-sectional data. Efforts deconvolute better understand such present remarkable translational opportunities developing targeted more effective interventions into Here, we Part I, a summary NIA Heterogeneity Successful Aging workshop virtually held May 2023.

Language: Английский

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Hallmarks of Cancer Cachexia: Sexual Dimorphism in Related Pathways

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 3952 - 3952

Published: April 22, 2025

Cancer-associated cachexia (CAC), also known as wasting syndrome, is a systemic condition that affects multiple tissues and organs via variety of metabolic pathways. Systemic inflammation, progressive weight loss, depletion adipose tissue, skeletal muscle impairment are some the hallmark features cachexia. Despite various studies on clinical CAC, complexity syndrome continues to pose significant challenges in practice, leading late diagnoses absence standardised treatment. Men women respond differently which may be prompted by pre-existing physiologic sex differences. This review presents sexual dimorphism associated with pathways involved CAC. A comprehensive understanding these could drive research prioritise inclusion more females related order achieve personalised sex-based therapeutic approaches and, consequently, enhance treatment efficacy better patient outcomes.

Language: Английский

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Emerging Technologies and Future Directions in Interorgan Crosstalk Cardiometabolic Research

Circulation Research, Journal Year: 2025, Volume and Issue: 136(11), P. 1494 - 1506

Published: May 22, 2025

The heart does not work in isolation, with cardiac health and disease occurring through complex interactions between the multiple organs. Furthermore, integration of organ-specific lipid metabolism, blood pressure, insulin sensitivity, inflammation involves a network signaling pathways many Dysregulation these communications is now recognized as key contributor to manifestations cardiovascular disease. Mechanistic characterization specific molecules mediating interorgan has been pivotal advancing our understanding discovery insulin, glucagon, other hormones early 20th century illustrated importance communication organs maintaining physiological homeostasis. For example, elegant studies evaluating its role regulating glucose metabolism have shed light on broader impact health, hypertension, atherosclerosis, risks. Recent technological advances revolutionized signaling. Global approaches such proteomics metabolomics applications enabled simultaneous profiling thousands circulating factors, revealing previously unknown pathways. These large-scale identified biomarkers linked stages offered new therapeutic targets. By how cells interact organs, kidney or liver, researchers can identify that, when disrupted, lead pathology. ability capture more holistic view system positions at forefront research. As we continue refine tools for mapping networks, insights gained hold potential only improve diagnosis but also develop targeted effective treatments In this review, discuss current used enhance organ crosstalk emphasis physiology.

Language: Английский

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Loss of CTRP10 results in female obesity with preserved metabolic health

Published: March 6, 2025

Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain metabolic profile free syndrome. The molecular underpinnings MHO, however, not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent unique female model MHO. CTRP10 modulates weight gain in striking sexually dimorphic manner. Female, but male, lacking develop obesity with age on low-fat diet while maintaining an otherwise profile. When fed obesogenic diet, Ctrp10 knockout (KO) show rapid gain. Despite pronounced obesity, KO do steatosis, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. largely uncoupled from dysregulation mice. Multi-tissue transcriptomic analyses highlighted gene expression changes pathways associated insulin-sensitive obesity. Transcriptional correlation the differentially expressed (DEG) orthologous humans also shows sex differences connectivity within across tissues, underscoring conserved sex-dependent function CTRP10. Collectively, our findings suggest negatively regulates body females, loss results benign preserved sensitivity health. This MHO mouse valuable understanding sex-biased mechanisms uncouple dysfunction.

Language: Английский

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