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To assess the determinants of exercise training-induced improvements in glucose control (HbA1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content. A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT). Changes in HbA1C were associated with changes in adiponectin (r = -0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = -0.26; P<0.03), and PGC-1α (r = -0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA1C. Decreases in HbA1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression. ClinicalTrials.gov NCT00458133.

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC-1α), termed the 'master regulator of mitochondrial biogenesis', has been implicated in stress and resilience to stress-induced depressive-like behaviours in animal models. However, there has been no study conducted to date to examine PGC-1α levels in patients with depression or in response to antidepressant treatment. Our aim was to assess PGC-1α mRNA levels in blood from healthy controls and patients with depression pre-/post-electroconvulsive therapy (ECT), and to examine the relationship between blood PGC-1α mRNA levels and clinical symptoms and outcomes with ECT. Whole blood PGC-1α mRNA levels were analysed in samples from 67 patients with a major depressive episode and 70 healthy controls, and in patient samples following a course of ECT using quantitative real-time polymerase chain reaction (qRT-PCR). Exploratory subgroup correlational analyses were carried out to determine the relationship between PGC-1α and mood scores. PGC-1α levels were lower in patients with depression compared with healthy controls (p = 0.03). This lower level was predominantly accounted for by patients with psychotic unipolar depression (p = 0.004). ECT did not alter PGC-1α levels in the depressed group as a whole, though exploratory analyses revealed a significant increase in PGC-1α in patients with psychotic unipolar depression post-ECT (p = 0.045). We found no relationship between PGC-1α mRNA levels and depression severity or the clinical response to ECT. PGC-1α may represent a novel therapeutic target for the treatment of depression, and be a common link between various pathophysiological processes implicated in depression.

Fission 1 (Fis1) plays a key role in mitochondrial division and is upregulated in pathological conditions, including trauma, sepsis, and ischemia-reperfusion injury. The goal of the study was to investigate Fis1 and other mitochondrial proteins involved in mitochondrial function and quality control as potential early biomarkers for the development of multiple organ dysfunction. We included all multiple trauma patients presenting to the hospital within 24 h of injury from September 1, 2022 to September 1, 2023. Patients were split into two groups the non-MODS group (n = 66) and the MODS group (n = 70) We obtained serum samples from all patients and using enzyme-linked immunosorbent assay (ELISA) measured concentrations of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), Fis1, mitofusin 2 (Mfn2), and Parkin. Concentrations of proteins were compared between groups and compared to a healthy control group. Additionally, demographic data and laboratory test results were collected from the patients. We used a logistic regression to identify if biomarkers were indepenteldy associated with the development of MODS. Within 24 h of injury, the median serum concentration of Parkin, Fis1, and PGC-1α, were significantly higher in the MODS group than in the control group. Similarily, compared to the non-MODS group, the median serum concentration of Fis1 and PGC-1α were significantly higher in the MODS group. Binary logistic regression analysis, adjusted for confounding factors, identified Fis1 as a predictive biomarker for MODS (OR = 1.006, 95 % CI: 1.002–1.009, P < 0.05)The area under the curve (AUC) for Fis1 in predicting MODS after multiple trauma was 0.777 (95 % CI: 0.698–0.857), indicating a moderate diagnostic value. This study found that in patients with multiple trauma, Fis1 concentrations are associated with the development of MODS. •First to evaluate serum MQC protein in multiple trauma, extending findings from sepsis studies.•Elevated Fis 1 may be an early biomarker for MODS post-trauma.•MQC proteins may offer noval therapeutic targets in trauma care.

Objectives To explore the associations between the levels of Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), Nitric oxide synthase (NOS), Runt-related transcription factor 2 (Runx2) and the delayed union of tibiofibular fractures, and to construct and validate a model for predicting the delayed union of tibiofibular fractures. Methods A total of 351 patients with tibiofibular fractures who were treated in the hospital from January 2022 to June 2024 were selected as the study subjects. They were randomly divided into a training set ( n  = 246) and a validation set ( n  = 105) at a ratio of 7:3. Experimental techniques such as ELISA were used to accurately detect the serum of patients, and multiple clinical data of the patients were comprehensively collected. Key influencing factors were screened out by statistical methods, such as univariate analysis and multivariate logistic regression analysis. Plot a nomogram and construct a prediction model, and use evaluation indicators to comprehensively evaluate and validate the model. Results In the training set, 72 cases (29.27%) had delayed union of tibiofibular fracture. Multivariate logistic analysis showed that fracture complexity, time from injury to surgery, levels of PGC-1α, NOS, Runx2, and OPG were independent influencing factors for the delayed union of tibiofibular fractures (all P  < 0.05). In the training set and the validation set, the C-index of the nomogram model was 0.760 and 0.711, respectively. The calibration curve showed moderate agreement between the predicted values and the actual values. The results of the Hosmer–Lemeshow test were χ 2  = 5.277, P  = 0.728 and χ 2  = 10.540, P  = 0.229, respectively. The ROC curve showed that in the training set and the validation set, the AUC of the nomogram model for predicting the delayed union of tibiofibular fractures was 0.760 (95% CI 0.680–0.839) and 0.711 (95% CI 0.581–0.842), respectively, and the sensitivity and specificity were 0.796, 0.645 and 0.739, 0.500, respectively. Conclusions This study provides a new perspective and method for the assessment of the delayed union of tibiofibular fractures, which is helpful for clinicians to potentially assist in risk stratification and closer follow-up for high-risk patients.

Objectives This study aimed to evaluate whether peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) could serve as a marker of myocardial ischemia by examining its association with cross-clamp time, which reflects the duration of ischemia, in patients undergoing coronary artery bypass grafting (CABG). Methods The study included 44 adult patients who underwent open-heart surgery at the Cardiovascular Surgery Clinic between June 2024 and December 2024. Serum samples separated from the blood collected after cross-clamping and at the pump outlet were analyzed in our hospital’s central laboratory for the PGC-1α study. PGC-1α levels were analyzed in terms of clinical parameters, lactate and high-sensitivity cardiac troponin T (hs-cTnT) levels of the patients. Results Preoperative PGC-1α levels did not differ significantly from postoperative levels (2.06 ± 5.75 vs. 1.43 ± 3.35, p  = 0.608), whereas hs-cTnT levels increased significantly after surgery ( p  < 0.001). Preoperative PGC-1α showed a moderate positive correlation with DM ( r  = 0.366, p  = 0.015) but no significant association with other clinical variables, including ICU duration ( r  = 0.078, p  = 0.616), glucose, or HbA1c (all p  > 0.05). In the multivariable analysis, DM (odds ratio [OR] = 3.060, p  < 0.05) and ICU duration (OR = 1.466, p  < 0.05) were independently associated with PGC-1α, whereas preoperative glucose and HbA1c were not. ROC analysis demonstrated that hs-cTnT showed a significant discriminative ability for cross-clamp time in non-DM patients (AUC = 0.844, 95% CI: 0.684–1.000, p  = 0.002), whereas this relationship was not observed in DM patients. In contrast, PGC-1α did not demonstrate a significant discriminative performance in either group (AUC = 0.300–0.535, p  > 0.05). Conclusion PGC-1α was not associated with cross-clamp time or conventional markers of acute myocardial injury in patients undergoing coronary artery bypass grafting, indicating that it does not reflect ischemic duration. In contrast, hs-cTnT levels were significantly associated with the cross-clamp time in non-diabetic patients, whereas this relationship was not observed in diabetic individuals. The association of PGC-1α with diabetes mellitus and ICU duration suggests that it may reflect metabolic status rather than acute myocardial injury.

Objective This study aimed to predict the bronchopulmonary dysplasia (BPD) in preterm infants with a gestational age(GA) < 32 weeks utilizing clinical data, serum mediator complex subunit 1 (MED1), and serum peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α). Methods This prospective observational study enrolled 70 preterm infants with GA < 32 weeks. The infants were categorized into two groups: non-BPD group( N  = 35) and BPD group( N  = 35), including 25 cases with mild BPD and 10 patients with moderate/severe subgroups. We performed multifactorial regression analysis to investigate the postnatal risk factors for BPD. Furthermore, we compared serum levels of biomarkers, including MED1 and PGC-1α, among infants with and without BPD at postnatal days 1, 7, 14, 28, and PMA 36 weeks. A logistic regression model was constructed to predict BPD’s likelihood using clinical risk factors and serum biomarkers. Results Serum levels of MED1 on the first postnatal day, PGC-1α on the 1st, 7th, and 28th days, and PMA at 36 weeks were significantly lower in the BPD group than in the non-BPD group ( P  < 0.05). Furthermore, the predictive model for BPD was created by combing serum levels of MED1 and PGC-1α on postnatal day 1 along with clinical risk factors such as frequent apnea, mechanical ventilation time > 7 d, and time to reach total enteral nutrition. Our predictive model had a high predictive accuracy(C statistics of 0.989) . Conclusion MED1and PGC-1α could potentially serve as valuable biomarkers, combined with clinical factors, to aid clinicians in the early diagnosis of BPD.

Proinflammatory cytokines and the novel myokine irisin, a cleavage product of FNDC5, have been found to play a role in obesity and type 2 diabetes mellitus (T2DM). Irisin has been shown to increase browning of adipose tissue, thermogenesis, energy expenditure, and insulin sensitivity, yet its association with inflammatory markers is still limited. Circulating irisin has been found to be increased in obesity, while in adult subjects with T2DM decreased levels have been found. However, data establishing the association of circulating irisin in children and adolescents with T2DM has not been described in the literature. The objective of this study was to determine irisin plasma concentration and its association with metabolic and adiposity markers and with hs-CRP, a surrogate marker of inflammation used in clinical practice, in a pediatric population with T2DM. A cross-sample of 40 Mexican children and adolescents aged 7-17 were recruited, 20 diagnosed with T2DM and 20 healthy controls. Plasma irisin levels were found to be lower in the T2DM group compared with controls, which could be attributed to a reduced PGC-1α activity in muscle tissue with a consequent decrease in FNDC5 and irisin expression. Irisin concentration was found to be positively correlated with HDL-c, LDL-c, and total cholesterol, while negatively correlated with BMI, waist circumference, and triglycerides. However, after multiple regression analysis, only HDL-c correlation remained significant. hs-CRP was higher in the T2DM group and positively associated with adiposity markers, unfavorable lipid profile, insulin levels, and HOMA-IR, but no association with irisin was found. Given the favorable metabolic effects attributed to irisin, the low plasma levels found in children and adolescents with T2DM could exacerbate the inflammatory and metabolic imbalances and the intrinsic cardiovascular risk of this disease. We propose an “irisin-proinflammatory/anti-inflammatory axis” to explain the role of irisin as a metabolic regulator in obesity and T2DM.

Background/Objetives: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Nutritional disorders, particularly cachexia, significantly impact morbidity and mortality in IPF but remain under-investigated. This study aimed to characterize cachexia phenotypes in IPF through morphofunctional assessment (MFA) and to evaluate their prognostic relevance, including the role of mitochondrial biomarkers. Methods: In this prospective bicenter study, 85 IPF patients underwent MFA including bioelectrical impedance vector analysis (BIVA), nutritional ultrasound (NU), and T12-level computed tomography (T12-CT) for body composition. Functional and strength assessments included timed up and go test (TUG) and handgrip strength (HGS), respectively. Cachexia was defined by Evans’ criteria, Martin’s CT-based criteria, and our IPF-specific proposed definition. Serum GDF-15 and PGC-1α levels were also measured. Results: Cachexia prevalence varied by definition: 24.71% (Evans), 29.5% (Martin) and 42.4% (IPF Cachexia Syndrome). Cachectic patients showed significantly lower muscle mass, function, and quality (measured by reduced muscle attenuation at T12-CT), along with higher GDF-15 and lower PGC-1α levels. The presence of IPF Cachexia syndrome (HR 2.56; 95% CI, 1.08–6.07; p = 0.033), GDF-15 > 4412.0 pg/mL (HR 3.21; 95% CI, 1.04–9.90; p = 0.042) and impaired TUG (>8 s) (HR 3.77; 95% CI, 1.63–8.71; 0.002) were all independently associated with increased 24-month mortality. Conclusions: Cachexia is prevalent in IPF and showed strong concordance between the three diagnostic criteria. The IPF Cachexia syndrome, based on comprehensive morphofunctional phenotyping, demonstrated superior discriminatory capacity. The addition of mitochondrial biomarkers may improve early detection and support personalized interventions to improve patient outcomes.

•The Gly482 Ser PPARGC1 A polymorphism and diets influence cholesterol outcomes.•An example of gene-environment interactions is evidenced.•Genotyping of PPARGC1 A may contribute to personalized dietary treatments. The aim of this study was to investigate the influence of two PPARGC1A gene polymorphisms on metabolic outcomes in response to two energy-restricted diets. A 4-mo nutritional intervention was conducted that involved two different hypo-energetic diets based on low-fat (LF) and moderately high-protein (MHP) dietary patterns. Unrelated subjects with excessive weight were genotyped for two PPARGC1A polymorphisms: Rs8192678 (Gly482Ser) and rs3755863 (G > A). Genotyping was performed by next-generation sequencing and haplotypes were screened. Anthropometric measurements and biochemical tests were assessed with standardized methods. Different cholesterol outcomes were observed by diet and Gly482Ser genotype. The Gly482 Gly homozygotes after an LF diet had lower reductions in total cholesterol (−9 mg/dL vs. −27 mg/dL; P = 0.017) and low-density lipoprotein cholesterol levels (−5 mg/dL vs. −18 mg/dL; P = 0.016) than the subjects who were carriers of 482 Ser allele. However, this finding was not recorded in the MHP group where Gly482 Gly homozygotes underwent similar cholesterol decreases as the 482 Ser allele carriers. Likewise, all genotype carriers had significant reductions in the frequencies of hypercholesterolemia (total cholesterol ≥200 mg/dL) except for Gly482 Gly homozygotes in the LF group. Meanwhile, the rs3755863 polymorphism and PPARGC1A haplotypes showed borderline effects with regard to cholesterol decreases. An energy-restricted MHP diet might be more beneficial than an LF diet to reduce serum cholesterol among subjects who are carriers of the PPARGC1A Gly482Gly genotype. The analysis of this genetic variant might be the basis for a precise, nutrigenetic management of hypercholesterolemia based on genetic makeup.

Background Athletes have a large extent of oxidant agent production. In the current study, we aimed to determine the influence of thyme extract on the endurance exercise performance, mitochondrial biogenesis, and antioxidant status in rats. Methods Twenty male Wistar rats were randomly divided into two groups receiving either normal drinking water (non-supplemented group, n  = 10) or thyme extract, 400 mg/kg, (supplemented group, n  = 10). Rats in both groups were subjected to endurance treadmill training (27 m/min, 10% grade, 60 min, and 5 days/week for 8 weeks). Finally, to determine the endurance capacity, time to exhaustion treadmill running at 36 m/min speed was assessed. At the end of the endurance capacity test, serum and soleus muscle samples were collected and their superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as well as malondialdehyde (MDA) concentration were measured. Protein expression of PGC-1α, as a marker of mitochondrial biogenesis, was also determined in the soleus muscle tissue by immunoblotting assay. Results Findings revealed that the exhaustive running time in the treatment group was significantly ( p  < 0.05) prolonged. Both serum and soleus muscle MDA levels, as an index of lipid peroxidation, had a threefold increase in the thyme extract supplemented group (t 18  = 8.11, p  < 0.01; t 18  = 4.98, p  < 0.01 respectively). The activities of SOD and GPx of the soleus muscle were significantly ( p  < 0.05) higher in the non-supplemented group, while there was no significant difference in serum SOD, GPx activities, and total antioxidant capacity between groups. Furthermore, thyme supplementation significantly ( p  < 0.05) decreased PGC-1α expression. Conclusions Thyme extract supplementation increased endurance exercise tolerance in intact animals, although decrease of oxidative stress and regulation of the PGC-1α protein expression are not considered as underlying molecular mechanisms.