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PubMed2025

Adiponectin receptor agonist, AdipoRon, restores hepatic clock gene expression in PCOS-associated NAFLD.

Persistent lower levels of adiponectin are associated with hyperandrogenism, predisposing PCOS women to NAFLD. This study elucidated the therapeutic potential of a small molecule adiponectin receptor agonist-AdipoRon, utilizing an in-vivo PCOS rat model mimicking the manifestation of PCOS along with hepatosteatosis. Our study demonstrated that Adiporon reduced lipid accumulation in PCOS-associated NAFLD by alleviating insulin resistance & lipogenesis. AdipoRon also reversed hyperandrogenism and adiponectin deficiency in PCOS animals. In addition, AdipoRon was found to restore altered PCOS-induced hepatic circadian gene expression (Bmal1, Clock, Per3, Cry2, Reverba, and Rora). Interestingly, at the epigenetic level, global transcription activation marks, i.e., H3K4me3, H3K9/14ac, and H3K36me2, were upregulated in disease conditions. Furthermore, our ChIP data confirmed that circadian genes Bmal1, Reverba, And Rora are epigenetically regulated. ChIP assay data showed an increased H3K36 dimethylation at the Bmal1 and Rora promoter, whereas a significant decrease was observed at the Reverbα promoter in PCOS-associated NAFLD. AdipoRon ameliorated these PCOS-induced epigenetic alterations, modulating the hepatic circadian gene expression. We present the preliminary evidence illustrating the epigenetic modulation of AdipoRon, thereby regulating hepatic circadian gene expression. This study provides insights regarding the therapeutic potential of AdipoRon in PCOS-associated NAFLD, which can be of profound clinical significance.

Animals↗

PubMed2026

Comparative adipokine profile in middle-aged master athletes, untrained adults, and young individuals.

BACKGROUND: Adipose tissue is an active endocrine organ involved in metabolic regulation and systemic inflammation, processes that are altered during aging. Nevertheless, the adipokine profile associated with lifelong physical training in master. athletes remains incompletely characterized. AIM: This study investigated circulating concentrations of adiponectin, leptin, resistin, insulin, and the leptin-to-adiponectin and adiponectin-to-resistin ratios in four male groups: endurance master athletes (ME), master sprinters (MS), untrained middle-aged adults (UMA), and untrained young adults (YU). METHODS: ME (n = 17, 50.5 ± 9.6 years), MS (n = 30, 50.3 ± 6.2 years), UMA (n = 16, 48.5 ± 7.5 years), and YU (n = 23, 23.7 ± 4.0 years) underwent anamnesis, anthropometric assessments, and serum concentrations of adiponectin, leptin, resistin, and insulin using commercial ELISA kits. RESULTS AND DISCUSSION: Significant group differences were observed for all variables (p < 0.001). UMA exhibited higher concentrations of leptin, insulin, and resistin, together with an elevated leptin-to-adiponectin ratio and a reduced adiponectin-to-resistin ratio compared with the other groups (p < 0.05). MS also presented higher leptin and insulin levels and an increased leptin-to-adiponectin ratio compared. with YU (p < 0.05), as well as a lower adiponectin-to-resistin ratio (p < 0.05). Overall, effect sizes were large across outcomes, and master athletes displayed a more favorable adipokine profile than untrained middle-aged adults, suggesting potential metabolic adaptations associated with lifelong training. CONCLUSIONS: Middle-aged master athletes exhibited a more favorable adipokine profile than untrained middle-aged adults, with values approaching those observed in young individuals.

Adipose tissue↗

PubMed2026

Effects of GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists on Inflammatory and Metabolic Biomarkers in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 receptor agonists improve cardiovascular outcomes in type 2 diabetes mellitus (T2DM), but their effects on inflammatory and oxidative biomarkers are not fully defined. MATERIALS AND METHODS: We searched PubMed, Ovid MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to 19 February 2026 for randomised controlled trials (RCTs) in adults with T2DM comparing a GLP-1RA or dual GIP/GLP-1 agonist with placebo or active therapy, and reporting C-reactive protein (CRP or high-sensitivity CRP [hs-CRP]), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), malondialdehyde (MDA) or adiponectin. Random-effects meta-analyses were conducted using standardised mean differences (SMDs). RESULTS: Forty-one RCTs were included. GLP-1RAs significantly reduced CRP/hs-CRP (27 studies, 1991 participants; SMD -0.37, 95% CI -0.59 to -0.14) and MDA (3 studies, 272 participants; SMD -0.98, 95% CI -1.65 to -0.30), and increased adiponectin (16 studies, 1327 participants; SMD 0.30, 95% CI 0.13 to 0.46). Pooled effects on IL-6 (17 studies, 1068 participants; SMD -0.14, 95% CI -0.37 to 0.10), TNF-α (16 studies, 1164 participants; SMD -0.25, 95% CI -0.61 to 0.12) and MCP-1 (7 studies, 450 participants; SMD -0.27, 95% CI -0.58 to 0.03) were not statistically significant, although MCP-1 decreased in sensitivity analyses. Across biomarkers, heterogeneity was moderate to high. Two tirzepatide RCTs (562 participants) showed a significant reduction in IL-6 (SMD -0.28, 95% CI -0.47 to -0.09) and a non-significant trend towards lower CRP/hs-CRP. CONCLUSIONS: In adults with T2DM, incretin-based therapies consistently lower CRP/hs-CRP, reduce oxidative stress (MDA) and increase adiponectin, while effects on IL-6 and TNF-α are more variable. These data support a selective anti-inflammatory and metabolic regulatory profile of GLP-1-based therapy, but heterogeneity and limited data for some biomarkers warrant cautious interpretation and further mechanistic studies. TRIAL REGISTRATION: PROSPERO number: CRD420261321430.

Humans↗

PubMed2024

Prenatal black carbon exposure and DNA methylation in umbilical cord blood.

BACKGROUND/OBJECTIVES: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts. METHODS: Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood. RESULTS: We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84). CONCLUSIONS: Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.

Humans↗

PubMed2024

Major depletion of insulin sensitivity-associated taxa in the gut microbiome of persons living with HIV controlled by antiretroviral drugs.

BACKGROUND: Persons living with HIV (PWH) harbor an altered gut microbiome (higher abundance of Prevotella and lower abundance of Bacillota and Ruminococcus lineages) compared to non-infected individuals. Some of these alterations are linked to sexual preference and others to the HIV infection. The relationship between these lineages and metabolic alterations, often present in aging PWH, has been poorly investigated. METHODS: In this study, we compared fecal metagenomes of 25 antiretroviral-treatment (ART)-controlled PWH to three independent control groups of 25 non-infected matched individuals by means of univariate analyses and machine learning methods. Moreover, we used two external datasets to validate predictive models of PWH classification. Next, we searched for associations between clinical and biological metabolic parameters with taxonomic and functional microbiome profiles. Finally, we compare the gut microbiome in 7 PWH after a 17-week ART switch to raltegravir/maraviroc. RESULTS: Three major enterotypes (Prevotella, Bacteroides and Ruminococcaceae) were present in all groups. The first Prevotella enterotype was enriched in PWH, with several of characteristic lineages associated with poor metabolic profiles (low HDL and adiponectin, high insulin resistance (HOMA-IR)). Conversely butyrate-producing lineages were markedly depleted in PWH independently of sexual preference and were associated with a better metabolic profile (higher HDL and adiponectin and lower HOMA-IR). Accordingly with the worst metabolic status of PWH, butyrate production and amino-acid degradation modules were associated with high HDL and adiponectin and low HOMA-IR. Random Forest models trained to classify PWH vs. control on taxonomic abundances displayed high generalization performance on two external holdout datasets (ROC AUC of 80-82%). Finally, no significant alterations in microbiome composition were observed after switching to raltegravir/maraviroc. CONCLUSION: High resolution metagenomic analyses revealed major differences in the gut microbiome of ART-controlled PWH when compared with three independent matched cohorts of controls. The observed marked insulin resistance could result both from enrichment in Prevotella lineages, and from the depletion in species producing butyrate and involved into amino-acid degradation, which depletion is linked with the HIV infection.

Humans↗

PubMed2026

Effects of Acute Low- and Moderate-Dose Alcohol on Chronic Disease-Related Biomarkers in Healthy Light and Heavy Drinkers.

BACKGROUND: Alcohol consumption is a major contributor to global chronic disease, with growing evidence indicating health risks even at low levels of intake. However, mechanistic understanding of these risks relies heavily on preclinical models and observational data, leaving a critical gap in controlled experimental evidence regarding how alcohol perturbs human biological systems in vivo. METHODS: The present study utilized plasma samples from a randomized, placebo-controlled trial to evaluate the effects of low-dose (0.35 g/kg) and moderate-dose (0.60 g/kg) alcohol on disease-relevant biomarkers in 32 healthy adults (mean age = 25.0 ± 3.8 years; 21 female/11 male), characterized by light (n = 15) or heavy (n = 17) drinking. This design enabled evaluation of effects across dose, timescale, and drinking history, as well as assessment of their interactions. Plasma was collected at prebeverage baseline and hourly for 4 h afterward. Immunoassays quantified 10 disease-related biomarkers: adiponectin, angiogenin, D-dimer, high-sensitivity C-reactive protein (hsCRP), Intercellular Adhesion Molecule-1 (ICAM-1), Lipocalin-2 (LCN2), Matrix Metalloproteinase-7 (MMP-7), Matrix Metalloproteinase-9 (MMP-9), soluble Receptor for Advanced Glycation End-products (sRAGE), and Triggering Receptor Expressed on Myeloid cells 2 (TREM2). RESULTS: Main effects of group indicated that even in this young healthy sample, heavy drinking status was associated with higher levels of adiponectin, angiogenin, ICAM-1, LCN2, and sRAGE, a profile suggesting altered vascular and metabolic activity. Acute alcohol administration induced changes in sRAGE and hsCRP. Specifically, moderate-dose alcohol triggered an increase in the immunoglobulin sRAGE, which may reflect an acute compensatory response to inflammation and/or oxidative stress. Compared to placebo, hsCRP was lower in the low-dose alcohol condition; however, this finding should be interpreted in light of CRP biology. MMP-7, MMP-9, and LCN2 showed time-dependent fluctuations that were independent of experimental condition, highlighting the critical importance of placebo-controlled designs to account for diurnal/postprandial variation in immune biomarkers. CONCLUSION: Findings provide translational evidence that alcohol is associated with multisystem biomarker changes relevant to chronic disease and that alcohol-related biomarker perturbations vary by dose and chronicity.

Humans↗

PubMed2026

Characteristics of Protein Profiling and Biomarkers in Aortic Regurgitation With Heart Failure.

BACKGROUND: Valvular heart disease, particularly aortic valve disease including stenosis and regurgitation, is a common heart disease. This study aimed to explore the protein profiling and the biomarkers in severe aortic valve disease and to provide new insights into the therapeutic strategy. METHODS: Blood samples from 80 subjects were collected and analyzed by data independent acquisition technique in 3 comparisons (mild/moderate-control, severe-control, and severe-mild/moderate) and validated by ELISA. The diagnostic value of differentially expressed proteins associated with severe valvular heart disease was also evaluated by the receiver operating characteristic curve. RESULTS: A total of 9976 peptides and 451 proteins were identified through liquid chromatography-tandem mass spectrometry analysis. From these, 64 in mild/moderate-control, 50 in severe-control, and 50 in severe-mild/moderate comparisons were identified as differentially expressed proteins. IGFBP7 (insulin-like growth factor-binding protein 7; 5581.0±697.0 ng/mL), DSG1 (desmoglein-1; 21.0±2.0 pg/mL), ADIPOQ (adiponectin; 26 686.0±3730 ng/mL), and JUP (junction plakoglobin; 10.2±0.6 ng/mL) levels in the severe group were significantly higher than that in the mild/moderate (P<0.05) group. Additionally, ADIPOQ and JUP levels in the severe group were also higher than that in control (P<0.001). Receiver operating characteristic curve analysis showed that IGFBP7, DSG1, JUP, and ADIPOQ had strong potential value to be associated with severe aortic valve disease. CONCLUSIONS: By constructing proteomics profile to identify the protein characteristics this study found that increased IGFBP7, DSG1, JUP, and ADIPOQ are the characteristics of proteins in patients with severe valvular heart disease. These findings provide new insight into the diagnosis and pathogenesis of valvular heart disease, particularly aortic valve disease.

Humans↗

PubMed2026

Metabolic and endocrine modulation of the gut-adipose tissue axis via pro-, pre-, and postbiotics in overweight dogs: A systematic review.

Canine obesity is a complex metabolic disorder driven by luminal dysbiosis, impaired gut barrier function, and metaflammation. Following PRISMA 2020 guidelines, this systematic review evaluated the efficacy of pro-, pre-, and postbiotics in modulating the gut-adipose tissue axis in overweight dogs (BCS ≥ 6/9) or diet-induced obesity models. Searches across PubMed and Dimensions (April 2026) identified seven eligible experimental trials. Results suggest that postbiotic Bifidobacterium animalis subsp. lactis CECT 8145 reduced postprandial glucose AUC by 6 % strictly during energy restriction. Pasteurized Akkermansia muciniphila postbiotics limited diet-induced weight gain, though glucoregulatory impacts were highly strain-specific (AKK2 reduced fasting glucose and insulin resistance indexes, whereas EB-AMDK19 exerted no significant effect). Specific probiotics (including Enterococcus faecium, Bifidobacterium lactis, Lactiplantibacillus plantarum and Bifidobacterium breve) attenuated fasting hyperinsulinemia and preserved circulating adiponectin, but lipid profile improvements (triglycerides and total cholesterol) were inconsistent across trials. In dogs, increased luminal short-chain fatty acids are not consistently mirrored by endocrine responses, so the coupling between microbial metabolites and incretin signaling remains incomplete. A critical lack of standardized reporting for species-validated insulin sensitivity metrics was identified. In conclusion, microbiome-targeted therapies, particularly inanimate postbiotics, may represent useful adjunctive strategies to mitigate metabolic dysregulation in obesogenic environments. However, clinical efficacy remains strictly strain-specific and dependent on host energy balance. Given the scarcity of high-certainty evidence, future trials must integrate dynamic physiological assessments with species-validated surrogate indexes alongside standardized dietary controls.

Animals↗

PubMed2026

Conditional eIF2A Deletion Suggests Extra-Adipose Mechanisms Underlying Metabolic Syndrome in Total-Body eIF2A Knockout Mice.

Dynamic regulation of protein synthesis is essential for metabolic homeostasis, with translation initiation playing a key role in this process. Emerging evidence strongly indicates that in addition to canonical eukaryotic initiation factors (e.g., eIF2, eIF4E) non-canonical factors, such as eukaryotic initiation factor 2A can modulate metabolic homeostasis. eIF2A is a highly conserved eukaryotic protein originally proposed to function analogously to bacterial IF2, promoting initiator Met-tRNAi recruitment to the 40S ribosomal subunit, though its precise mechanism remains debated. To investigate its organismal role, we have previously generated the total-body eIF2A knockout mouse, which revealed eIF2A functions in lipid homeostasis, glucose tolerance, insulin sensitivity, and susceptibility to metabolic syndrome. To further determine whether adipose tissue drives these phenotypes, we presently generated adipose-specific eIF2A knockout mice. Despite dysregulation of some key adipokines, including for example, adiponectin, these mice did not develop metabolic syndrome, even under high-fat diet conditions, indicating that adipose tissue specific deficiency of eIF2A is insufficient to reproduce the metabolic defects observed in total-body knockout. However, we found that eIF2A deficiency in the liver of the total body eIF2A-KO mice can independently drive metabolic syndrome components via translational control of Lpin1 (a phosphatidate phosphatase and a transcriptional coactivator) that controls hepatic lipid storage and metabolism. eIF2A deficiency in the liver leads to disruption of fatty acid oxidation and the production of ketone bodies, not observed in adipose-specific eIF2A knockout mice. Our findings suggest that systemic metabolic effects observed in the total body eIF2A-KO mice may arise from coordinated functions across multiple organs.

adipose tissue↗

PubMed2024

Acute physical exercise and ambulatory blood pressure in resistant hypertension.

OBJECTIVES: The effects of acute physical exercise in patients with resistant hypertension remain largely unexplored compared with hypertensive patients in general. We assessed the short-term effects of acute moderate-intensity (MICE) and high-intensity interval exercise (HIIE) on the clinic (BP) and 24-h ambulatory blood pressure (ABP) of patients with resistant hypertension. METHODS: Using a crossover randomized controlled design, 10 participants (56 ± 7 years) with resistant hypertension performed three experimental sessions: MICE, HIIE, and control. MICE consisted of continuous treadmill exercise at an intensity of 3-4 metabolic equivalents of energy (METs) until completing 3 kcal/kg and was energy-matched to HIIE (which included six to eight intervals of 3 min duration at 6-7 METs interspersed with 1.5-min rests at 3 METs). In the control session, participants remained seated for 50 min. Flow-mediated vasodilation, autonomic nervous system balance (heart rate variability), exerkines [interleukin (IL)-6, IL-8, IL-15, vascular endothelial growth factor A, irisin, adiponectin, and angiopoietin] and 71 inflammatory-related proteins were also measured. RESULTS: Compared with baseline, HIIE and MICE reduced clinic SBP immediately ( P  < 0.001 for both) and 90 min ( P  = 0.001 and P  = 0.041, respectively) postexercise. HIIE and MICE also reduced clinic DBP immediately postexercise ( P  = 0.003 and P  = 0.025). By contrast, no changes were found in the control session. On the other hand, no significant effects were noted for 24 h ABP measures or for the rest of variables. CONCLUSION: Although in patients with resistant hypertension, acute aerobic exercise induces short-term reductions in clinic BP, this stimulus does not suffice to reduce 24 h ABP or to impact on potential biological mechanisms.

Humans↗

PubMed2025

Scalable Deep Learning of Histology Images Reveals Genetic and Phenotypic Determinants of Adipocyte Hypertrophy.

BACKGROUND: White adipose tissue dysfunction has emerged as a critical factor in cardiometabolic disease development, yet the cellular microstructure and genetic architecture of adipocyte morphology remain poorly explored. METHODS: We introduce Adipocyte U-Net 2.0, an advanced deep learning method for the semantic segmentation of adipose tissue histology, enabling analysis of over 27 million adipocytes from 2,667 individuals. FINDINGS: Our approach revealed that adipocyte hypertrophy associates with metabolic dysfunction, including increased fasting glucose, glycated hemoglobin, leptin, and triglycerides, with decreased adiponectin and HDL cholesterol levels. Through the largest genome-wide association study of adipocyte size to date (NSubcutaneous = 2,066, NVisceral = 1,878), we identified four genome-wide significant loci: two in sex-combined analysis (rs73184721 in NAALADL2 and rs200047724 in NRXN3) and two female-specific variants (rs140503338 and rs11656704 in ULK2). Notably, these genetic associations showed congruent relationships with cardiometabolic traits, suggesting shared biological mechanisms. INTERPRETATION: Our findings demonstrate the utility of deep learning for adipocyte phenotyping at scale and provide novel insights into the genetic basis of adipocyte morphology and its relationship to metabolic disease.

Journal Article↗

PubMed2026

Large-Scale Proteomic Profiling of Incident Heart Failure and Its Subtypes in Older Adults.

BACKGROUND: Heart failure (HF) and its main subtypes, heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), impose an enormous health burden on elders. Assessment of the circulating proteome to illuminate pathogenesis could open new opportunities for treatment. METHODS: We conducted a plasma proteomics screen of incident HF and its subtypes in 2 older population-based cohorts, the CHS (Cardiovascular Health Study) and the AGES-RS (Aging, Gene/Environment Susceptibility-Reykjavik Study). The 2 studies used SomaLogic platforms, with 4404 aptamers in common. Multivariable Cox models were fit to evaluate individual-protein associations with HF, HFpEF, and HFrEF separately in each cohort, and study-specific associations were combined by fixed-effects meta-analysis. Replication was performed in the ARIC (Atherosclerosis Risk in Communities) cohort. Two-sample Mendelian randomization of HF and its subtypes, along with colocalization analysis, was performed to support causal inference. RESULTS: Among 8599 participants, 1590 experienced incident HF (536 HFpEF, 471 HFrEF). There were 119 proteins associated with HF, 15 proteins with HFpEF, and 11 proteins with HFrEF, at Bonferroni-corrected significance. Among these, 9 have never previously been identified for cardiovascular diseases, and another 61 represent new associations with incident HF or its subtypes. Of these 70 proteins, 55 of the 66 available replicated externally. Mendelian randomization analysis revealed 7 proteins genetically associated with HF at nominal significance; 2 were separately associated with HFpEF, and another 2 with HFrEF. Seven of these 9 proteins (NPDC1 [neural proliferation differentiation and control protein 1], APOF [apolipoprotein F], LMAN2 [lectin, mannose-binding 2], ADIPOQ [adiponectin], CD14 [cluster of differentiation 14], ARHGAP1 [Rho GTPase-activating protein 1], C9 [complement 9]) showed new, possibly causal associations, although we did not detect evidence for colocalization. CONCLUSIONS: In this large-scale proteomic study involving 3 longitudinal cohorts of older adults, we identified and replicated 55 novel protein markers of HF or its subtypes, and 7 new, possibly causal proteins. These proteins may enhance risk prediction, improve understanding of pathobiology, and help prioritize targets for therapeutic development of these foremost disorders in elders.

Humans↗

PubMed2025

Integrative analyses of mendelian randomization and bioinformatics reveal casual relationship and genetic links between COVID-19 and knee osteoarthritis.

BACKGROUND: Clinical and epidemiological analyses have found an association between coronavirus disease 2019 (COVID-19) and knee osteoarthritis (KOA). Infection with COVID-19 may increase the risk of developing KOA. OBJECTIVES: This study aimed to investigate the potential causal relationship between COVID-19 and KOA using Mendelian randomization (MR) and to explore the underlying mechanisms through a systematic bioinformatics approach. METHODS: Our investigation focused on exploring the potential causal relationship between COVID-19, acute upper respiratory tract infection (URTI) and KOA utilizing a bidirectional MR approach. Additionally, we conducted differential gene expression analysis using public datasets related to these three conditions. Subsequent analyses, including transcriptional regulation analysis, immune cell infiltration analysis, single-cell analysis, and druggability evaluation, were performed to explore potential mechanisms and prioritize therapeutic targets. RESULTS: The results indicate that COVID-19 has a one-way impact on KOA, while URTI does not play a causal role in this association. Ribosomal dysfunction may serve as an intermediate factor connecting COVID-19 with KOA. Specifically, COVID-19 has the potential to influence the metabolic processes of the extracellular matrix, potentially impacting the joint homeostasis. A specific group of genes (COL10A1, BGN, COL3A1, COMP, ACAN, THBS2, COL5A1, COL16A1, COL5A2) has been identified as a shared transcriptomic signature in response to KOA with COVID-19. Imatinib, Adiponectin, Myricetin, Tranexamic acid, and Chenodeoxycholic acid are potential drugs for the treatment of KOA patients with COVID-19. CONCLUSIONS: This study uniquely combines Mendelian randomization and bioinformatics tools to explore the possibility of a causal relationship and genetic association between COVID-19 and KOA. These findings are expected to provide novel perspectives on the underlying biological mechanisms that link COVID-19 and KOA.

Humans↗

PubMed2025

Exploring the therapeutic potential of extract in targeting localized adiposity.

OBJECTIVE: To determine direct targeting of localized adiposity through Morus alba Linne bark injection based on pharmacology network analysis. METHODS: Male C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. After 6 weeks on HFD, the water extract of Morus alba L.bark (MAB, 2 mg/mL) was locally injected into one inguinal fat pad, while saline was injected into the other side, 3 times/week for 6 weeks (n = 6/group). The water extract of MAB was freeze-dried and then diluted in saline before use. RESULTS: HFD-fed mice treated with local MAB topical injection showed reduced adipocyte weight and size in inguinal fat pads by dual-energy X-ray absorptiometry. No toxicity changes seen in liver, spleen, kidney tissue, or alanine aminotransferase / aspartate aminotransferase levels in serum by MAB injection. Protein levels of phosphorylated insulin receptor substrate-1 and glucose transporter type 4, and mRNA expression of adiponectin, were increased in inguinal adipose tissue injected with MAB locally. Locally MAB injection led to a decrease in glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, linked to gluconeogenesis, while forkhead box protein O1, which regulates these factors, was increased. Moreover, there was an increase in adenosine 5'-monophosphate-activated protein kinase, related to lipogenesis, as well as elevated levels of hormone-sensitive lipase and fatty acid synthase, both associated with lipolysis. These results support the 'insulin signaling pathway' and 'regulation of lipolysis in adipocytes' identified in the Kyoto Encyclopedia of Genes and Genomes pathway through network analysis. CONCLUSION: This study suggests that MAB topical injection exhibits localized fat reduction by inhibiting insulin resistance, gluconeogenesis and lipogenesis mediator, while activating lipolysis enzymes within targeted adipose site.

Animals↗

PubMed2026

Suggestive genome-wide associations with inflammatory biomarkers in an admixed population, including a missense variant in the OR6K6 olfactory receptor gene associated with MCP-1.

BACKGROUND: Chronic low-grade inflammation drives cardiometabolic diseases and has a strong genetic basis. Most genome-wide association studies (GWAS) have focused on European populations, limiting knowledge of the genetic influences on inflammation in admixed populations such as those in Brazil. METHODS: This study is part of the cross-sectional ISA Capital Health Survey. It uses data from the 2015 ISA Nutrition cohort, which measured biochemical, genetic, anthropometric, and lifestyle factors in a probabilistic sample of São Paulo residents. Genomic DNA was extracted from 841 individuals. Genotyping was performed using the Axiom 2.0 Precision Medicine Research Array. After quality control and missing data exclusion, 244,338 SNPs from 638 individuals remained for GWAS-based association analysis with eight inflammatory biomarkers. Models were adjusted for sex, age, age2, overweight, and the first two principal components of ancestry. RESULTS: Most participants were male (53%) and not overweight (55%). The median age was 49, and 38% were older adults. In the genome-wide analysis of TNF-α, IL-10, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and adiponectin, 12 SNPs were significantly associated, most of which were intronic. Notably, one signal mapped to the missense variant rs16841009 in the olfactory receptor gene OR6K6. This variant was associated with MCP-1, suggesting a possible involvement in inflammatory responses. CONCLUSIONS: We identified new SNPs linked to inflammatory biomarkers in a highly admixed Brazilian population, including a missense variant in an olfactory receptor gene linked to MCP-1. This association may be biologically important for inflammation and could affect the risk of cardiometabolic diseases.

Humans↗

PubMed2026

CTRP9 ameliorates heart failure with preserved ejection fraction by regulating lipid metabolism.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major clinical challenge, with cardiac lipotoxicity emerging as a key driver of disease progression. Despite CTRP9’s role in lipid metabolism and cardioprotective properties, its therapeutic potential in HFpEF remains unexplored. This study aimed to investigate whether CTRP9 ameliorates HFpEF by regulating cardiac lipid metabolism and to identify the underlying molecular mechanisms. METHODS: In the established two-hit HFpEF mouse model (induced by a high-fat diet and L-NAME), the mice were treated with either CTRP9 or saline. Cardiac function was evaluated by echocardiography, while hypertrophy, fibrosis, and lipid accumulation were assessed using histology and molecular assays. Proteomic sequencing was further employed to identify downstream targets of CTRP9. RESULTS: CTRP9 treatment significantly improved diastolic function and attenuated cardiac hypertrophy and fibrosis in HFpEF mice. Myocardial lipid accumulation was substantially reduced, accompanied by enhanced fatty acid oxidation. Proteomic analysis identified GPD1 as a key downstream target upregulated by CTRP9. Cardiac-specific knockdown of GPD1 partly abolished the therapeutic benefits of CTRP9. CONCLUSION: Our data suggest that CTRP9 ameliorates HFpEF through GPD1-mediated regulation of cardiac lipid metabolism, identifying the CTRP9-GPD1 axis as a promising therapeutic target for HFpEF.

Animals↗