Search Results (411)

Obesity is a complex metabolic disorder associated with dyslipidemia, insulin resistance, and hepatic steatosis. Given its multifactorial nature, multi-component therapeutic strategies have attracted increasing interest, particularly herbal formulations containing diverse bioactive compounds. This study investigated the anti-obesity and hepatoprotective effects of a mixed herbal extract, JH01, composed of Curcuma longa, Achyranthes bidentata, and Polygonum multiflorum, using a screening-based analytical approach combined with experimental validation. Individual herbal extracts and their mixture were screened at 100 and 500 μg/mL in 3T3-L1 adipocytes. Based on superior anti-adipogenic efficacy, JH01 was selected for further study. Its effects were evaluated in vitro by Oil Red O staining and quantitative real-time PCR analysis of adipogenic genes, and in vivo using a high-fat diet (HFD)-induced obese mouse model, assessing body weight, serum lipid profiles, liver function markers, adipokine levels, and hepatic histology. JH01 showed markedly stronger inhibition of lipid accumulation than individual herbal components. JH01 significantly suppressed adipocyte differentiation and downregulated PPARγ, C/EBPα, and SREBP-1 expression in 3T3-L1 cells. Furthermore, JH01 modulated inflammatory cytokines and adipokine levels, as evidenced by reduced TNF-α, IL-6, and IL-1β levels and increased adiponectin levels. In HFD-fed mice, JH01 reduced body weight gain, serum triglyceride and total cholesterol levels, improved ALT and AST levels, decreased leptin concentrations, and attenuated hepatic steatosis. JH01 exerts potent anti-obesity and hepatoprotective effects through coordinated regulation of lipid metabolism and adipogenesis, supporting its potential as a multi-herbal therapeutic strategy for obesity-related metabolic disorders. Full article

Marine macroalgae are increasingly recognized as sources of bioactive compounds with potential benefits for metabolic health. This study investigated the chemical composition and metabolic effects of a 70% ethanol extract of the edible red alga Gracilaria coronopifolia in a high-fat diet (HFD)-induced obesity model in rats. Chemical profiling using liquid chromatography–high-resolution mass spectrometry (LC–HRMS) identified several classes of metabolites, including sterols, phenolic acids, flavonoids, and fatty acid derivatives such as palmitoleic acid, chlorogenic acid, gallic acid, and quercetin. Male Wistar rats were fed an HFD for 11 weeks to induce obesity and subsequently treated with G. coronopifolia extract (40–160 mg/kg body weight) for 28 days, with semaglutide (70 µg/kg) used as a pharmacological comparator. Supplementation with the extract significantly reduced obesity-related parameters compared with untreated HFD controls. The highest extract dose (160 mg/kg) decreased final body weight from 294.8 ± 43.3 g in HFD rats to 215.2 ± 11.9 g, reduced visceral fat mass from 22.7 ± 2.37 g to 7.63 ± 1.19 g, and lowered the adiposity index from 6.39 ± 0.45% to 3.31 ± 0.22%. The extract also improved serum lipid profiles, reducing triglyceride levels from 185.46 ± 11.58 mg/dL in the HFD group to 101.54 ± 24.29 mg/dL, while increasing HDL concentrations to 75.64 ± 4.73 mg/dL. In addition, treatment increased adiponectin levels (to 779.55 ± 15.66) and decreased leptin (4.94 ± 0.75) and amylin (532.44 ± 30.00) relative to obese controls. Histological analysis demonstrated a reduction in adipocyte hypertrophy. Gene expression analysis revealed downregulation of hypothalamic Npy and adipose Fas and Pparγ, together with upregulation of Pomc, Mc4r, and Cpt1. These findings suggest that G. coronopifolia extract improves metabolic disturbances associated with diet-induced obesity through coordinated regulation of appetite signaling and lipid metabolism, supporting its potential development as a marine-derived functional food ingredient. Full article

Background: Chromophobe renal cell carcinoma (ChRCC) is characterized by the accumulation of abnormal mitochondria, a high rate of mitochondrial DNA (mtDNA) mutations, and altered oxidative metabolism. There are no existing circulating biomarkers to distinguish metastatic ChRCC from clear cell renal cell carcinoma (ccRCC). Methods: High-throughput plasma proteomic profiling using the SomaScan platform was performed in 18 ChRCC (including 16 metastatic ChRCC) and 197 metastatic ccRCC patients. Data were harmonized to generate a unified 7K-protein matrix. Results: Differential expression analysis was performed using limma (version 3.62.2). Of 7272 quantified human plasma proteins, 209 were differentially expressed between ChRCC and ccRCC. Upregulated proteins in ChRCC included essential β-oxidation enzymes such as ECH1 (enoyl-CoA hydratase 1) and ECI1 (enoyl-CoA delta-isomerase 1), suggesting increased long-chain fatty acid degradation. Creatine and energy-buffering pathways were also represented, with increased CKMT1A (Creatine Kinase, Mitochondrial 1A) in ChRCC. KIM-1 (Kidney Injury Molecule-1) and leptin were lower in ChRCC, consistent with the known upregulation of these proteins in ccRCC. Pathway enrichment analyses revealed an overrepresentation of mitochondrial protein degradation, fatty acid β-oxidation, and respiratory electron transport in ChRCC, suggesting that ChRCC sheds a unique mitochondrial signature into the peripheral circulation. A bootstrap-based LASSO logistic regression restricted to upregulated mitochondrial proteins in ChRCC vs. ccRCC consistently selected ECI1 and CKMT1A. The LASSO model achieved an AUROC of 0.964. Conclusions: Compared to ccRCC, the plasma proteome of metastatic ChRCC is dominated by mitochondrial metabolic enzymes, revealing a systemic metabolic phenotype strikingly aligned with the known histologic accumulation of abnormal mitochondria in ChRCC cells. Full article

Background/Objectives: Among more than 300 candidate genes for obesity, FTO, MC4R, and BDNF have been approved for DTC genetic testing. However, population-specific evidence supporting their relevance to obesity-related phenotypes in Koreans remains limited. Methods: A total of 231 healthy adults aged 19–64 years were recruited between March and May 2024. Anthropometric and clinical measurements, genotyping, dietary intake, and questionnaires on socioeconomic status, family history, and lifestyle behaviors were obtained. Associations between genotypes and obesity-related phenotypes were evaluated using ANOVA and ANCOVA, multivariable-adjusted models and multicollinearity analysis-based stepwise regression. Results: In Koreans, MAFs for FTO (3 SNPs), MC4R rs17782313 and BDNF rs6265 were 13–16%, 27.1% and 47.4%, respectively. OB frequency (%) differed significantly between BDNF GG and A allele carriers (p < 0.05). Compared to GG, BDNF A allele carriers showed higher WHR, ALT, HbA1c and sodium intake (p < 0.05). BDNF A allele carriers were observed to have higher drinking frequency and elevated ALT levels. Significant genotype–obesity interactions were identified for RMR/BW status, dietary fiber, Vit E, folate, P, K, cholesterol, and PUFA (p < 0.05). Among A allele carriers, OB-related indicators (BMI, RMR, WHR) were independently associated with age, sex, RMR, SBP, ALT, leptin, and dietary intakes of Vit A and sugars. Conclusions: These findings support the relevance of BDNF rs6265 in obesity phenotypes among Korean adults and provide Korean-specific evidence for genotype-based nutrition strategies. Given the cross-sectional study, the interpretation of personalized nutrition approaches for genetic risk carriers should be made with caution. Full article

Neuroplacentology is an emerging field of research supporting that the placenta actively contributes to the fetal brain development through the release of bioactive molecules. Recent angiogenesis-focused data showed that prenatal alcohol exposure (PAE) disrupts inter-organ gene expression between the placenta and fetal cortex. The present study aimed to perform the first comprehensive and untargeted analysis of a murine placenta–cortex transcriptomic database of PAE. Gene lists from a recently NCBI-deposited PAE Placenta–Cortex transcriptomic database were analyzed using g:Profiler for unbiased functional profiling querying Gene Ontology, KEGG, and Reactome databases. Genes intersecting with cell–cell communication terms were submitted to STRING and ShinyGO analyses to identify enriched protein–protein interactions and pathways. Several ligand or receptor candidates were then validated by Western blot. g:Profiler revealed 21 enriched GO functional maps, seven KEGG pathways, and six Reactome pathways, of which 11 were related to cell-to-cell communication. STRING analysis exhibited substantial protein–protein interaction enrichments supporting that proteins belonging to the functional maps and pathways are biologically connected. Notably, 38 ligands or receptors from endocrine families including angiotensinogen, leptin, somatostatin, or PACAP were identified. Western blot analysis of protein candidates showed different validation patterns. In particular, the PACAP receptor family confirmed transcriptomic findings and revealed sex-dependent PAE-impacted expression profiles. The present study indicates that PAE is associated with alterations in the transcriptomic placenta–cortex expression profile, including changes in the expression ratios of several ligands and/or receptors implicated in key physiological pathways such as energy balance, vascular development, and neurogenesis. These transcriptomic associations suggest that altered placenta–fetal brain signaling at the gene expression level may be involved in alcohol-induced neurodevelopmental disorders, highlighting the need for future functional validation studies. Full article

Background/Objectives: Obesity is characterized by dysregulated hypothalamic energy homeostasis and reduced central responsiveness to the anorexigenic hormones leptin and insulin. β-Hydroxybutyrate (β-HB), a major ketone body, has recently garnered attention as a signaling metabolite. However, its effects on hypothalamic leptin and insulin responsiveness remain unclear. This study aimed to investigate the effects of β-HB on hypothalamic hormone responsiveness and the associated molecular mechanisms, primarily using a high-fat diet (HFD)-induced obese mouse model. Methods: Male mice were fed an HFD to induce obesity and treated with β-HB via oral or intracerebroventricular (ICV) administration. Feeding behavior following leptin and insulin administration was evaluated, and activation of hypothalamic leptin-induced STAT3 signaling and insulin-induced Akt signaling was analyzed. In addition, mRNA expression of inflammation-related and appetite-regulating genes was assessed by quantitative PCR. Normal mice also received chronic ICV administration of β-HB from the onset of HFD feeding, and changes in body weight and cumulative food intake were measured. Results: Both oral and ICV administration of β-HB significantly enhanced the anorexigenic responses to leptin and insulin in HFD-induced obese mice. At the molecular level, leptin-induced STAT3 phosphorylation and insulin-induced Akt phosphorylation were enhanced in the hypothalamus. Gene expression analysis revealed reduced SOCS3 and TNFα expression and increased POMC expression. Furthermore, chronic ICV administration of β-HB from the onset of HFD feeding significantly suppressed body weight gain and the increase in cumulative food intake. Conclusions: This study demonstrates that β-HB improves hypothalamic leptin and insulin responsiveness in obese mice and modulates the associated molecular environment. These findings suggest that β-HB acts as a metabolically responsive signaling molecule regulating hypothalamic function, providing a basis for novel metabolic intervention strategies against obesity. Full article

Background/Objectives: The aim of this study was to investigate the association between the rs7799039 variant in the leptin (LEP) gene and specific parameters of body composition in young healthy Slovak adults using bioelectrical impedance analysis. Methods: We assessed 467 young adults aged 18 to 30 years with an average age of 22.55 ± 2.56 years. Genotyping of SNP LEP G-2548A (rs7799039) was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and body composition was assessed by bioelectrical impedance analysis (InBody 770). Results: Our results showed that the LEP rs7799039 variant was associated with total body mineral levels in women. The mean values of total body minerals (kg) were higher in LEP AA carriers than in carriers of the G allele (3.26 ± 0.52 kg compared to 3.09 ± 0.36 kg; p = 0.014). In addition, linear regression analysis showed statistically significant associations of the LEP gene rs7799039, vitamin D intake, body mass index (BMI) and height on total body mineral content in women (p < 0.05). The presence of the LEP AA genotype, reported vitamin D intake and higher BMI and height values were positively associated with higher total body mineral content. No association was found between the LEP rs7799039 variant and BMI, fat mass (FM) or FM distribution across body segments. Conclusions: Our data suggest that the rs7799039 variant in the LEP gene may be associated with small differences in total body mineral content in young adult women. These findings should be interpreted as exploratory associations, rather than evidence of biological specificity or an independent genetic effect. Full article

Objective: This double-blind, parallel-group randomized controlled trial is the first to investigate the synergistic effects of interval resistance plus progressive aerobic training with fisetin supplementation on adipokines in obesity. Methods: Sixty sedentary men with obesity (BMI < 30 kg/m²) completed 12 weeks of thrice-weekly interval resistance training (eight exercises, 3 × 13 reps at 60% 1RM with 20% 1RM active rest), immediately followed by staged aerobic bouts (50–70% HRmax). Participants were randomized into the control-placebo (P), fisetin (F; 200 mg/day), training-placebo (TP), or training + fisetin (TF) groups. The primary outcomes were asprosin, MCP-1, and adiponectin; secondary outcomes included leptin and lipid profile. Data were analyzed via ANCOVA with Bonferroni post hoc tests. Results: Statistical analyses were conducted following the intention-to-treat (ITT) principle using an analysis of covariance (ANCOVA) model, which revealed extensive effects of the interventions on the participants’ anthropometric and biochemical indices. Regarding body composition, after adjusting for baseline values, a significant difference in mean body weight was observed between groups (F (3, 55) = 9.444, p < 0.001, ηp² = 0.340); Bonferroni post hoc tests confirmed that the training plus fisetin (TF), training-placebo (TP), and fisetin (F) groups all achieved significant weight loss compared to the placebo (P) group. Furthermore, body mass index (BMI) showed a significant inter-group difference (p = 0.021), with post hoc analysis revealing that only the TF group reached a statistically significant reduction compared to the placebo (p = 0.024; 95% CI [−3.760, −0.172]). In the assessment of biochemical and inflammatory variables, the interventions exerted a highly significant effect on asprosin (F (3, 55) = 36.047, p < 0.001; ηp² = 0.663) and MCP-1 (F (3, 55) = 29.570, p < 0.001; ηp² = 0.617). The findings indicated that the TF group experienced the most substantial reductions in both asprosin (−60.71%) and MCP-1 (−46.50%) levels. Regarding adipokines, significant increases in adiponectin levels were observed in the TP (29.38%) and TF (27.67%) groups (p < 0.05), whereas changes in leptin were statistically significant only in the TF group relative to the placebo (p = 0.049). The lipid profile results indicated a statistically significant difference in the TF group in improving all markers; this group achieved greater reduction compared to other groups, including reductions in LDL-C, triglycerides (TG), and total cholesterol (TC) (p < 0.001), while simultaneously showing a significant elevation in HDL-C. Post hoc analyses confirmed robust statistical differences in all lipid parameters for both the TF and TP groups compared to the placebo group (p < 0.05), whereas the placebo group experienced a deterioration in status characterized by a significant increase in LDL-C (p = 0.027) and a significant decline in HDL-C concentrations (p = 0.006). Conclusions: In conclusion, 12 weeks of combined interval resistance–aerobic training and fisetin supplementation significantly reduced pro-inflammatory adipokines and improved lipid profiles in obese men. These findings suggest that asprosin serves as a potential modulator in metabolic risk reduction; however, since direct mechanistic assays were not conducted, these implications remain hypothetical. Future research employing molecular readouts is warranted to confirm the underlying pathways involved. Full article

Background/Objectives: The study aimed to examine the association between the total SPPB score and serum leptin levels in patients with coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI). Methods: A cross-sectional study included 204 prospectively enrolled patients with CAD who were admitted for elective PCI. The mean age was 67.45 ± 8.63 years; 63.2% of patients were male. The Short Physical Performance Battery (SPPB) was used to screen for prefrailty and frailty (10–12 points: no frailty; 8–9 points: prefrailty; ≤7 points: frailty). The levels of leptin, a biomarker of fat remodeling, were measured by a highly sensitive and highly specific enzyme immunoassay using a Diagnostics Biochem Canada Inc. Leptin ELISA Kit (London, ON, Canada). Results: The prevalence of frailty and prefrailty in patients with stable CAD was 20.1% and 40.2%, respectively. A comparative analysis revealed that frailty was significantly more likely in older women with CAD before elective PCI. The total serum leptin level was 13.00 [8.00–50.00] ng/mL. Frail patients with CAD had higher leptin levels than patients without frailty (25.40 [7.00–60.00] ng/mL vs. 12.00 [5.15–19.70] ng/mL, p = 0.037). The leptin level in patients with prefrailty was 16.70 [13.00–49.10] ng/mL. Moreover, there was a moderate inverse correlation between the total SPPB score and serum leptin levels before PCI (p = 0.006). A regression analysis found that the total SPPB score in patients with stable CAD was associated with high serum leptin levels (p < 0.001) and older age (p = 0.017). Conclusions: Our study found that frail patients with CAD undergoing PCI had higher serum leptin levels than patients without frailty. Full article

Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment for localized PCa, and PCa mortality. A key mechanistic link contributing to this enhanced risk is chronic inflammation originating from excess white visceral adipose tissue (WAT; VAT) and periprostatic adipose tissue (ppWAT). Contributing to systemic inflammation is gut dysbiosis, which itself may be caused by ABCD as well as background local inflammation (prostatitis), which is common in aging men and may be exacerbated by the urinary microbiome. Investigating the molecular biology driving inflammation and its association with increased PCa risk, a recent paper applied a network and gene set enrichment to adipokine drivers in the ABCD-PCa network. It found prominent roles for MCP-1, IL-1β, and CXCL-1 in addition to confirming the importance of exposure to lipopolysaccharides and bacterial components, corroborating the role of gut dysbiosis. To further unravel the mechanistic links between ABCD and PCa risk, this critical review will discuss the current literature on prominent inflammatory signaling pathways activated in ABCD; the influence of gut dysbiosis, the urinary microbiome, and chronic prostatitis; and current hypotheses on how these domains may result in the development of aggressive PCa over a man’s life. Moreover, we performed a novel pathway enrichment analysis to further evaluate the associations between ABCD, PCa risk, gut dysbiosis, and the prostate microbiome, the results of which were partitioned into extracellular and intracellular signaling pathways. In the extracellular space, novel mechanistic links between gut dysbiosis and MCP-1, IL-1β, CXCL1, and leptin via bacterial pathogen signaling and the intestinal immune network (for IgA production), crucial for gut immune homeostasis, were found. Within the intracellular space, there were downstream signals activating chemokine and type 2 interferon pathways, focal adhesion PI3K/Akt/mTOR pathways, as well as the JAK/STAT, NF-κB, and PI3K/Akt pathways. Overall, these findings point to an emerging molecular pathway for PCa oncogenesis influenced by ABCD, gut dysbiosis, and inflammation, and further research, possibly with lifestyle program-based clinical trials, may discover novel biomarker panels and molecular targeted therapies for the prevention and treatment of PCa. Full article

Background/Objectives: Obesity-associated hyperleptinemia has been linked to breast cancer (BC) progression via mechanisms that remain incompletely understood. This study explores the role of leptin and its receptor (LEPR) in facilitating BC cell proliferation, migration, epithelial–mesenchymal transition (EMT), and STAT3 signaling pathway activation. Methods: We analyzed gene expression and survival data from TCGA BRCA dataset. MCF-7 and MDA-MB-231 BC cells were exposed to leptin at 10 ng/mL (lean-associated levels) and 100 ng/mL (elevated levels linked to obesity). MTT assays, colony formation tests, wound-healing and tumor spheroid dissemination experiments evaluated cell proliferation and migration. Immunofluorescence and Western blot analysis assessed changes in EMT markers and cytoskeletal alterations, while Western blotting and qPCR assessed STAT3 and NCOA1 expression and activation levels. Results: Elevated LEPR expression was linked with unfavorable prognosis in BC patients. Higher doses of leptin (100 ng/mL) significantly enhanced cellular proliferation rates and migratory capabilities, in both cell lines, and promoted EMT characteristics marked by downregulated E-cadherin and cytoskeleton structural changes. Whereas heightened JAK2/STAT3 signaling correlated with elevated leptin dosages, STAT3 inhibition using AG490 reversed leptin-induced migration while reinstating E-cadherin levels to baseline. Furthermore, leptin upregulated NCOA1, an essential STAT3 coactivator, facilitating increased expression of Cyclin D1 and VEGF target genes. Clinical positive relationships were seen between LEP/LEPR expressions and NCOA1 levels and between NCOA1 and various gene signatures related to STAT3/P-STAT3 within BC specimens. Conclusions: Obesity-associated hyperleptinemia enhances aggressiveness in BC through a mechanism involving LEPR-mediated activation pathways encompassing NCOA1/STAT3, which drive proliferation, migration, and EMT. This assigns a potential therapeutic utility for obesity-related advancements found within BC pathology. Full article

The increasing prevalence of obesity-related primary arterial hypertension (PAH) in the pediatric population emphasizes the need to develop new biomarkers that can aid in clinical practice for prevention or early diagnosis of the cardiovascular disease. The objective of the present study was to evaluate the relationship between selected adipokines, cytokines, and blood pressure (BP) values in children with obesity. A total of 78 children participated in the study: 60 children with obesity (study group) and 18 children with normal weight (control group). Blood pressure was measured according to guidelines. Serum levels of metabolic and inflammatory markers, including leptin, adiponectin, resistin, ghrelin, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α), vascular endothelial growth factor (VEGF), and insulin were determined using multiplex immunoassays. Statistical analysis included correlation and ROC tests to identify potential predictors of PAH. The study group had significantly higher systolic and diastolic BP compared to the control group (p < 0.0001). Serum levels of leptin, IL-6, VEGF, insulin, and resistin were increased in the study group. Leptin, IL-6 and resistin correlated positively with BP values (p < 0.05), while ghrelin and adiponectin correlated negatively. ROC analysis identified leptin, IL-6, and VEGF as the most promising biomarkers for predicting PAH. The results confirm the role of adipokines and cytokines in the pathogenesis of PAH. The assessment of adipokine and cytokine profiles complements traditional anthropometric parameters such as BMI in assessing cardiovascular risk. Leptin, IL-6, and VEGF presented the strongest correlation with hypertension, suggesting their potential in future diagnostic and preventive strategies. Full article

Monogenic forms of severe early-onset obesity often involve genetic disruptions in the hypothalamic leptin-melanocortin pathway. Pathogenic variants in the SIM1 gene, a key transcription factor required for the development of the paraventricular nucleus, are a known cause of Prader–Willi-like syndrome, characterized by hyperphagia, severe obesity, and developmental delay. We performed targeted next-generation sequencing of 52 obesity-associated genes on a cohort of pediatric patients with severe early-onset obesity. Identified variants were analyzed for population frequency and predicted pathogenicity using in silico tools. The structural impact of the novel missense variants was assessed using protein domain modeling with AlphaFold3. We identified five rare SIM1 variants in eleven patients. Four were heterozygous nonsynonymous variants: one frameshift in the bHLH domain (p.Ser18Ter), one frameshift in the Per-ARNT-Sim domain (p.His143Ter), and two missense variants, p.Pro30Ala and p.Ser663Leu. Structural modeling suggested that the missense variants are likely to disrupt critical protein–protein interactions. The fifth variant was a synonymous change, c.1173G>A, p.(Ser391Ser), which was detected in five unrelated patients. Bioinformatic analysis predicted that this variant could alter splicing. Structural modeling suggested that the missense variants interfere with SIM1 function. This study expands the mutational spectrum of SIM1-linked monogenic obesity, reporting novel likely pathogenic frameshift variants, a missense variant, and a recurrent synonymous variant with a potential splice-site effect. The majority of the variants are predicted to affect the SIM1 protein. Our findings strengthen the critical role of the SIM1 gene in hypothalamic development and energy homeostasis. The results underscore the importance of including the SIM1 gene in genetic testing panels for children with severe obesity and hyperphagia, enabling precise diagnosis and potential future personalized management. Functional in vitro or in vivo validation of these variants is required to confirm their pathogenicity. Full article

Background/Objectives: Both HIV infection and antiretroviral therapy contribute to dyslipidemia and abnormal body fat distribution in people living with HIV (PLWH). Exercise training is an effective intervention to protect against these metabolic changes. However, little is known about the mechanisms underlying the impact of exercise training on lipid metabolism in PLWH. This study aimed to comparatively evaluate the effect of high-intensity functional circuit training on the plasma lipidome of PLWH and HIV-negative subjects (control). Methods: PLWH (n = 13) and control (n = 14) were submitted to 8 weeks of exercise training. Body composition, anthropometric, and biochemical parameters were measured. Plasma was obtained in a fasting state for lipidomic analysis. Results: Anthropometric and biochemical parameters revealed lower levels of leptin, HDL-C, body fat %, and BMI combined with elevated aspartate transaminase (AST) and Homeostasis Model Assessment of β-cell function (HOMA_beta) in PLWH when compared to control subjects that persisted from baseline to post-exercise training. Nonetheless, contrasting levels of adiponectin, fasting insulin, and phosphatidylcholine-containing lipids observed at baseline were equalized after training in PLWH. In control subjects, significant reductions in concentrations of triglycerides alongside phosphatidylinositol and glycosylated ceramides were observed post-exercise training. By contrast, PWLH displayed an increase in diglycerides, acylcarnitines, and free cholesterol levels after exercise training, together with decreased concentrations of free fatty acids, cholesteryl esters, and glycosylated ceramides. Conclusions: In addition to specific lipidome alterations in each group, particularly driven by improved insulin resistance in PLWH, this study showed concomitant modulation of several glycerophospholipids and sphingolipids, suggesting health-promoting effects of short-term exercise training. Collectively, these modulated lipid species represent interesting targets for future lipidomic-based studies evaluating not only the effects of exercise training but also the molecular mechanisms resulting in a healthier plasma lipidome profile. Full article

Mesenchymal stromal cells (MSCs) are multipotent and play an important role in regenerative processes such as wound healing. Data on possible changes and functional restrictions of MSCs due to cisplatin chemotherapy, for example, in the treatment of head and neck cancer, diverge. The aim of this study was to evaluate the influence of cisplatin on MSCs with regard to their defining characteristics and their ability to differentiate and to migrate. MSCs from four human donors (a 59-year-old man, a 63-year-old woman, a 70-year-old man, and a 61-year-old man) were cultured in vitro with and without cisplatin for 24 h, and toxic and subcytotoxic concentrations were determined using an MTT. We then examined the surface phenotype markers (flow cytometry), migration (scratch assay), histological differentiation markers (adipo-, chondro-, osteogenic), and the expression of selected line-associated genes in real-time quantitative PCR (RT-qPCR) (LEP, SOX9, RUNX2). These characteristics were evaluated after treatment with different subcytotoxic, clinically relevant doses of cisplatin. Flow cytometry confirmed the presence of MSCs-characteristic surface markers, which remained stable under treatment with subcytotoxic doses of cisplatin. Cisplatin exposure reduced the mRNA abundance of leptin (a marker for adipogenic differentiation) but increased SOX9 mRNA abundance (chondrogenic differentiation). RUNX (osteogenic differentiation) did not change post cisplatin exposure. Histological analysis showed no difference with regard to osteogenic, chondrogenic, and adipogenic differentiation at doses up to 10 μM cisplatin. Cell migration was not restricted by cisplatin exposure under the conditions used here. The characteristics of MSCs were not different to controls post cisplatin exposure. mRNA analysis suggested induced changes by cisplatin, although this effect was not histologically detectable even at high doses. Based on the single-molecule markers used here, indications for an inhibitory effect of cisplatin on adipogenic differentiation and a rather enhancing effect on chondrogenic and osteogenic differentiation may be hypothesized. The process observed here could further aggravate the already serious problem of malnutrition in head and neck cancer patients, for example. Taken together though, our study confirms overall MSCs tolerance towards cisplatin. Full article