BACKGROUND: Weight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need. OBJECTIVE: Identification of predictive factors associated with successful weight loss after sequential exercise in women with obesity. METHODS: The study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures. RESULTS: Recruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026. CONCLUSIONS: This intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67570.

• Klíčová slova
• diabetes, endocrinology, exercise, gut microbiota, metabolic flexibility, obesity, overweight, physical activity, protocol, randomized control trial, validation study, weight loss,
• MeSH
• cvičení fyziologie   MeSH
• diabetes mellitus 2. typu prevence a kontrola   MeSH
• dospělí MeSH
• hmotnostní úbytek fyziologie   MeSH
• inzulinová rezistence MeSH
• klinické křížové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita * terapie   metabolismus   MeSH
• randomizované kontrolované studie jako téma MeSH
• výsledek terapie MeSH
• životní styl * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

Later stages of secondary lymphedema are associated with the massive deposition of adipose tissue (AT). The factors driving lymphedema-associated AT (LAT) expansion in humans remain rather elusive. We hypothesized that LAT expansion could be based on alterations of metabolic, adipogenic, immune and/or angiogenic qualities of AT. AT samples were acquired from upper limbs of 11 women with unilateral breast cancer-related lymphedema and 11 healthy women without lymphedema. Additional control group of 11 female breast cancer survivors without lymphedema was used to assess systemic effects of lymphedema. AT was analysed for adipocyte size, lipolysis, angiogenesis, secretion of cytokines, immune and stem cell content and mRNA gene expression. Further, adipose precursors were isolated and tested for their proliferative and adipogenic capacity. The effect of undrained LAT- derived fluid on adipogenesis was also examined. Lymphedema did not have apparent systemic effect on metabolism and cytokine levels, but it was linked with higher lymphocyte numbers and altered levels of several miRNAs in blood. LAT showed higher basal lipolysis, (lymph)angiogenic capacity and secretion of inflammatory cytokines when compared to healthy AT. LAT contained more activated CD4+ T lymphocytes than healthy AT. mRNA levels of (lymph)angiogenic markers were deregulated in LAT and correlated with markers of lipolysis. In vitro, adipose cells derived from LAT did not differ in their proliferative, adipogenic, lipogenic and lipolytic potential from cells derived from healthy AT. Nevertheless, exposition of preadipocytes to LAT-derived fluid improved their adipogenic conversion when compared with the effect of serum. This study presents results of first complex analysis of LAT from upper limb of breast cancer survivors. Identified LAT alterations indicate a possible link between (lymph)angiogenesis and lipolysis. In addition, our in vitro results imply that AT expansion in lymphedema could be driven partially by exposition of adipose precursors to undrained LAT-derived fluid.

• MeSH
• cytokiny genetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipolýza MeSH
• lymfedém související s rakovinou prsu genetika   metabolismus   MeSH
• lymfedém genetika   metabolismus   MeSH
• přežívající onkologičtí pacienti MeSH
• regulace genové exprese MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• studie případů a kontrol MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cytokiny MeSH

In aging, the capacity of subcutaneous adipose tissue (SAT) to store lipids decreases and this results in metabolically unfavorable fat redistribution. Triggers of this age-related SAT dysfunction may include cellular senescence or endoplasmic reticulum (ER) stress. Therefore, we compared lipogenic capacity of SAT between young and older women and investigated its relation to senescence and ER stress markers. Samples of SAT and corresponding SAT-derived primary preadipocytes were obtained from two groups of women differing in age (36 vs. 72 years, n = 15 each) but matched for fat mass. mRNA levels of selected genes (lipogenesis: ACACA, FASN, SCD1, DGAT2, ELOVL6; senescence: p16, p21, NOX4, GDF15; ER stress-ATF4, XBP1s, PERK, HSPA5, GADD34, HYOU1, CHOP, EDEM1, DNAJC3) were assessed by qPCR, protein levels of GDF15 by ELISA, and mitochondrial function by the Seahorse Analyzer. Compared to the young, SAT and in vitro differentiated adipocytes from older women exhibited reduced mRNA expression of lipogenic enzymes. Out of analyzed senescence and ER stress markers, the only gene, whose expression correlated negatively with the expression of lipogenic enzymes in both SAT and adipocytes, was GDF15, a marker of not only senescence but also mitochondrial dysfunction. In line with this, inhibition of mitochondrial ATP synthase in adipocytes strongly upregulated GDF15 while reduced expression of lipogenic enzymes. Moreover, adipocytes from older women had a tendency for diminished mitochondrial capacity. Thus, a reduced lipogenic capacity of adipocytes in aged SAT appears to be linked to mitochondrial dysfunction rather than to ER stress or accumulation of senescent cells.

• Klíčová slova
• Aging, Lipogenesis, Mitochondrial dysfunction, Senescence, Stress of endoplasmic reticulum, Subcutaneous adipose tissue,
• MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace MeSH
• chaperon endoplazmatického retikula BiP MeSH
• dospělí MeSH
• lidé MeSH
• lipogeneze * MeSH
• mitochondrie metabolismus   MeSH
• podkožní tuk metabolismus   MeSH
• růstový diferenciační faktor 15 metabolismus   MeSH
• senioři MeSH
• stárnutí buněk MeSH
• stárnutí metabolismus   MeSH
• stres endoplazmatického retikula MeSH
• tukové buňky metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• GDF15 protein, human MeSH Prohlížeč
• HSPA5 protein, human MeSH Prohlížeč
• růstový diferenciační faktor 15 MeSH

BACKGROUND/OBJECTIVES: OxLDL-β2GPI complex has been suggested to have a role in the development of atherosclerosis and other inflammatory diseases. The aim of this study was to investigate the possible association of circulating oxLDL-β2GPI with obesity-induced inflammatory state of adipose tissue and related comorbidities as metabolic syndrome development. SUBJECTS/METHODS: Two cohorts of subjects were examined in the study. Cohort I: 36 women with wide range of body mass index (17-48 kg m-2) and metabolic status (with or without metabolic syndrome (MS); cohort II: 20 obese women undergoing a dietary intervention (DI) consisting of 1-month very-low-calorie diet, and 5 months of weight-stabilization period. Serum levels of oxLDL-β2GPI were measured by enzyme-linked immunosorbent assay. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp and homeostasis model assessment of insulin resistance. mRNA expression of macrophage markers was determined in both subcutaneous (SAT) and visceral (VAT) adipose tissue in cohort I and in SAT in cohort II. RESULTS: Serum oxLDL-β2GPI levels were increased in obese subjects with MS compared to lean or obese without MS (obese with MS: 26.6±5.0 vs lean: 15.17±1.97, P<0.001; vs obese without MS: 16.36±2.89, P<0.05). Serum oxLDL-β2GPI correlated with MS indices (glucose, high-density lipoprotein, triglyceride and ureic acid) and with mRNA expression of macrophage markers in VAT. Weight-reducing DI decreased serum oxLDL-β2GPI levels together with lipid parameters and the mRNA expression of inflammatory markers in SAT. CONCLUSIONS: OxLDL-β2GPI seems to be an important marker of visceral adipose tissue inflammation and possibly a factor contributing to insulin resistance and metabolic syndrome development in obese patients.

• MeSH
• beta-2-glykoprotein I krev   chemie   metabolismus   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny LDL krev   chemie   metabolismus   MeSH
• metabolický syndrom krev   patofyziologie   MeSH
• multiproteinové komplexy MeSH
• obezita * krev   metabolismus   patofyziologie   MeSH
• tuková tkáň metabolismus   patofyziologie   MeSH
• zánět krev   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-2-glykoprotein I MeSH
• biologické markery MeSH
• lipoproteiny LDL MeSH
• multiproteinové komplexy MeSH
• oxidized low density lipoprotein MeSH Prohlížeč

Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.

• MeSH
• dospělí MeSH
• genové regulační sítě genetika   MeSH
• hmotnostní úbytek genetika   fyziologie   MeSH
• kalorická restrikce * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• obezita metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH