bims-mimead 2026-06-28 papers

BMC Geriatr. 2026 Jun 23.

Exercise training is associated with changes in adipocyte size and lipid metabolism in older women: cross-sectional and longitudinal study.

Marek Wilhelm, Terezie Čížková, Klára Daďová, Michal Koc, Jana Neubert, Ondřej Kuda, Jan Gojda, Lenka Rossmeislová, Michaela Šiklová.

Adaptations in subcutaneous adipose tissue (SAT) metabolism may contribute to cardiometabolic health improvements in response to exercise training, especially during aging. Here we investigated the potential effects of long- and short-term exercise on adipogenesis and lipid metabolism in adipose tissue of older women (age 61-80 years). The effects of long-term (> 5 years) physical activity and short-term (4 months) exercise training were evaluated, with a focus on adipocyte size, adipogenic capacity, gene expression related to lipolysis, lipogenesis, and peroxisomal β-oxidation, along with lipidomic and proteomic analysis.The difference between long-term physically active/physically fit (Trained) and less physically active (Sedentary) older women was analyzed in cross-sectional study (Sedentary, n = 29: age 72 ± 4 yrs, BMI 25.9 ± 2.6 kg/m2; Trainedn = 28: age 69 ± 4 yrs, BMI 25.1 ± 2.3 kg/m2). The effect of short-term exercise training (ET) was observed during 4-months of combined ET in group of 23 women (age 70 ± 4 yrs, BMI 27.2 ± 4.1 kg/m2).Both physical activity durations were associated with reduced adipocyte hypertrophy, which was driven by changes in adiposity. No significant changes in adipose capacity to differentiate was observed. Long-term physical activity increased mRNA expression of β-adrenergic receptors (ADRB1, ADRB2) and elevated very-long chain fatty acid (VLC-FA) levels, correlating positively with cardiorespiratory fitness (VO2, peak). Altogether, these findings suggest novel hypotheses regarding SAT metabolic adaptations that may support metabolic health in older women, warranting further investigation in larger cohorts.New & noteworthyOur study reveals that SAT adipogenic capacity remains largely unaffected by physical activity in older women. However, the observed link between elevated β-adrenergic receptor expression, VLC-FA levels, and fitness suggests potential adipose tissue-specific adaptations that might mediate the positive effects of exercise in older age.

Keywords: Adipogenesis; Adipose tissue; Exercise training; Lipid metabolism; Older women

DOI: https://doi.org/10.1186/s12877-026-07752-9

Mol Syst Biol. 2026 Jun 23.

Quantitative interactome mapping of skeletal muscle insulin resistance.

Yaan-Kit Ng, Ronnie Blazev, Julian P H Wong, Nichollas E Scott, Jeffrey Molendijk, Benjamin L Parker.

Protein-protein interactions (PPIs) are dynamic and critical to adaptive homeostasis. While there have been massive efforts to catalogue proteome-wide PPIs, global quantification of changes remains a challenge. Here, we integrate dynamic protein correlation profiling - mass spectrometry (PCP-MS) and quantitative cross linking-mass spectrometry (qXL-MS) using multiplexed stable isotope labelling to characterise global PPI remodelling following the development of chronic skeletal muscle insulin resistance (IR) with or without acute insulin stimulation. We quantify >7,000 unique PPIs amongst 5,346 proteins and show changes in the interactome network dominate the proteome response. Our data show the dysregulation of protein processing in the endoplasmic/sarcoplasmic reticulum involving changes in PPIs with protein chaperones and disulfide isomerases is a major hallmark of skeletal muscle IR. Mechanistically, we show the dysregulation of PPIs with Protein-Disulfide Isomerase 6 (PDIA6) regulates cysteine oxidation and insulin sensitivity. Taken together, we show in vivo quantitative interactome mapping is a powerful approach to understand disease mechanisms and provide new insights into protein network re-organisations with IR.

DOI: https://doi.org/10.1038/s44320-026-00224-7

Nat Aging. 2026 Jun 26.

Meta-analysis of DNA methylation aging signatures in 17 human tissues.

Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD+ metabolism, supporting NAD+ as a potential therapeutic target in aging. A gene encoding a cell-adhesion protein, PCDHGA1, emerged as a conserved hub across tissues, implicating cell-to-cell communication pathways in aging across multiple organs. Our methylation atlas therefore provides a resource for dissecting the molecular basis of human aging and for identifying potential biomarkers and translational therapies.

DOI: https://doi.org/10.1038/s43587-026-01164-5

Steroids. 2026 Jun 24. pii: S0039-128X(26)00085-1. [Epub ahead of print] 109823

Development and validation of an LC-MS method for quantification of sex steroid hormones in skeletal muscle.

Viktor Engman, Séverine Lamon, Shaun Mason.

Sex steroid hormones are not exclusively localised in the circulation and can be found in numerous extragonadal tissues, in concentrations unrelated to the circulating fraction. Existing methodology to measure intramuscular steroid hormone concentrations includes both immune-based assays and liquid chromatography-mass spectrometry (LC-MS), the gold standard for hormone measurements. To date, no LC-MS based methods validation has been published on the measurement of intramuscular sex steroid hormones, despite clear biological relevance. Here, we describe the development and validation of a simple, high-throughput LC-MS Orbitrap method for the measurement of 10 intramuscular sex steroid hormones, namely pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, epitestosterone, dihydrotestosterone, oestrone, oestradiol, and oestriol. In brief, isotope labelled standards were added to 5-6 mg of lyophilised muscle tissue, homogenised and extracted with ethyl acetate. The extracts were dried down and sequentially derivatised with 1-methylimidazole-2-sulfonyl chloride and hydroxylamine hydrochloride to target both the phenolic hydroxy groups and oxo groups. The limit of detection was 1.0 ± 1.0 pg/mg (range 0.36-3.26 pg/mg), with a R2 > 0.99 for all analytes. Matrix effects were 90-110% for all analytes except for dihydrotestosterone (143.6%), and precision was <10 CV% for all analytes in the presence of a muscle matrix. Our method allows for 20-40 samples to be prepared in ~4 h, with a sample data acquisition time of 13 min. Moreover, our method provides the opportunity for specific analysis of steroid hormone concentrations in skeletal muscle, allowing target tissue specificity instead of relying on proxy measures from the circulation.

Keywords: Hormone; Muscle; Orbitrap; Testosterone

DOI: https://doi.org/10.1016/j.steroids.2026.109823

EMBO Rep. 2026 Jun 22.

E4BP4 safeguards brown fat mitochondria from obesity-induced fragmentation via ceramide repression.

Fernando Valdivieso-Rivera, Vanessa O Furino, Carlos E Leher, Ariane M Zanesco, Monara Kaélle Cruz, Flavia C Gan, Adriana Leandra Santoro, Lara Regina-Ferreira, Giovanna Leite Santos, Tiago Gonçalves, Luiz Osório Leiria, Pedro M Moraes-Vieira, Roger Frigério Castilho, Shingo Kajimura, Marcelo A Mori, Licio A Velloso, Carlos H Sponton.

Brown adipose tissue (BAT) counteracts obesity-related metabolic dysfunction through both thermogenic and non-thermogenic means. However, substantial evidence indicates that obesity negatively affects BAT mitochondrial morphology and oxidative capacity, impairing systemic energy homeostasis. Motivated by this apparent contradiction, we investigate the relationship between obesity and mitochondrial dynamics, as the underlying mechanisms remain incompletely understood. Here, we identify E4BP4 as a transcriptional repressor that prevents obesity-induced mitochondrial fragmentation and oxidative dysfunction by inhibiting ceramide synthesis in brown fat. Specifically, E4BP4 interacts with PRDM16 to repress Cers6 mRNA expression and consequently reduces C16:0 ceramide levels by binding to a 65 kb upstream enhancer region of the Cers6 gene. Notably, the preservation of mitochondrial integrity in BAT by E4BP4 gain-of-function improves systemic glucose homeostasis, independent of weight loss. Collectively, our findings establish E4BP4 as a molecular safeguard against obesity-induced mitochondrial fragmentation and oxidative dysfunction, primarily by suppressing ceramide synthesis in brown fat.

DOI: https://doi.org/10.1038/s44319-026-00826-0

Metabolism. 2026 Jun 22. pii: S0026-0495(26)00194-0. [Epub ahead of print] 156683

Ghrelin predicts food consumption up to three hours prior to eating: A randomised controlled trial.

Oliver J Hulme, Christoffer Martinussen, Barbara Vad Andersen, Maria Saur Svane, Jens Juul Holst, Kirstine Nyvold Bojsen-Møller, Bolette Hartmann, Jens Frederik Rehfeld, Søren Gregersen, Kjeld Hermansen, Derek V Byrne, Hartwig Roman Siebner, Sten Madsbad.

Eating triggers a cascade of metabolic, neural, and subjective signals that unfold and interact over several hours, typically suppressing the motivation to eat until the next meal. Which of these signals predict next-meal intake is not well understood. In a cross-over, double-blinded, and repeated measures factorial design over four separate test days, we manipulated both the protein and caloric content of four preload meals to experimentally induce differences in satiety. We investigated how the neural, subjective, hormonal, and metabolite states unfolded after a meal and how much each of them predicted the next meal intake 3 h later. Bayesian analysis revealed an extreme level of evidence for the inclusion of the peptide hormone ghrelin as a predictor of next meal energy intake. This predictive effect was consistently found for all time points, including also the time point immediately preceding preload consumption. When measured immediately before the ad libitum test meal, the plasma level of the gut hormone Glucagon-like Peptide-1 (GLP-1) and the subjective report of estimated consumption also predicted next-meal intake. No other measure, including the protein and caloric content of the preload, adequately predicted next-meal intake. Our results link ghrelin levels with the regulation of food intake several hours later.

Keywords: Appetite suppression; Food intake; Ghrelin; Hunger; Satiety

DOI: https://doi.org/10.1016/j.metabol.2026.156683