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Associations between mental health, diet, and risk of Alzheimer's disease highlight the need to investigate whether dietary patterns moderate the relationship between symptoms of depression and anxiety, and neurodegeneration-related blood-based biomarkers. Cognitively unimpaired participants (n = 89) were included from the Australian Imaging, Biomarkers and Lifestyle study (mean age 75.37; 44 % male). Participants provided dietary, depressive and anxiety symptom data, and had measurement of blood-based biomarkers. Dietary pattern scores (Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension diet (DASH), and Western diet) were generated. Moderation and simple slope analyses were employed. In males with mean and below mean MeDi adherence, depressive symptoms were associated with higher neurofilament light (NfL) levels. In Apolipoprotein E ε4 non-carriers with lower than mean and mean MeDi adherence, depressive symptoms were associated with higher NfL and Aβ40 levels. No associations were observed between DASH and Western diets and neurodegeneration-related biomarkers. MeDi adherence is potentially a moderator of the relationship between depressive symptoms and neurodegeneration-related blood-based biomarkers, with sex- and genotype-specific approaches important to consider within this relationship. [Display omitted] • Examined diet's role in depression and neurodegeneration risk. • Included 89 cognitively healthy older adults, mean age 75.37 years. • Males with low MeDi adherence showed higher NfL with depressive symptoms. • High-risk individuals with depression and poor MeDi had elevated biomarker levels. • MeDi may moderate the depression and neurodegeneration relationship. [ABSTRACT FROM AUTHOR]

Background: There's a scarcity of drugs effective against nonalcoholic steatohepatitis (NASH). Exosomes from Human umbilical cord mesenchymal stem cells (huc-MSCs) show potential in managing glycolipid metabolism and the immune response. Therefore, further investigations are required to explore their application in NASH and the underlying mechanisms. Methods: C57BL/6J mice were fed with a western diet for 12 weeks to induce NASH, and huc-MSCs exosomes (MSCs-exo) were administered during the feeding period. The effect of MSCs-exo was evaluated by monitoring changes in body weight, fat distribution, blood glucose, and insulin levels, and analyzing pathological alterations in liver tissue. Mechanism investigations were carried out using flow cytometry, immunofluorescence staining, and other experimental techniques. Results: MSCs-exo could reduce liver fat, inflammation, fibrosis, and improved metabolism to alleviate the progression of NASH. Besides, MSCs-exo could decrease macrophage accumulation in the liver, encouraging M2 over M1 macrophage polarization. Furthermore, our study found that MSCs-exo had a high expression of miR-24-3p, which may regulate macrophage polarization by targeting the interferon-stimulated genes (STING) gene in macrophages, with its overexpression amplifying MSCs-exo's NASH benefits. Conclusions: These findings suggest that the therapeutic effect of MSCs-exo on NASH may be attributed to the regulation of macrophage M2 polarization through miR-24-3p targeting STING. This provides a scientific basis for future clinical application. [ABSTRACT FROM AUTHOR]

Background: The complexity of the galaninergic system is still not fully understood, especially under specific pre-existing comorbidities related to metabolic dysfunction. A plant-derived triterpenoid celastrol was demonstrated to exert a complex effect on the galaninergic system and to have hepatoprotective and anti-obesity properties. However, the exact molecular mechanisms responsible for these effects remain unclear. Specifically, there are no data on the impact of celastrol on the heart and liver galaninergic system. Therefore, this study aimed to investigate the effects of celastrol on the galaninergic system expression in the heart and liver of mice suffering from diet-induced obesity and metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD/MASH). Methods: The male mice C57BL/6J were fed a Western-type high-fat diet for 16 and 20 weeks to induce obesity and MASLD/MASH. Celastrol was administered along with a specific diet for the last 4 weeks to evaluate its impact on the progression of these conditions. Moreover, the inhibitor of sterol regulatory element-binding protein 1/2 (SREBP1/2), fatostatin, was also tested to compare its influence on the galaninergic system with celastrol. Results: The study demonstrates that celastrol treatment was safe and led to a reduction in food and energy intake, body fat and liver weights, and MASLD-to-MASH progression and improved glucose tolerance, serum biochemistry markers, and hepatic lipid peroxidation in mice. Quantitative gene expression originally showed significant regulation of galanin and all three of its receptors (GalR1/2/3) in the heart ventricles and only GalR2 in the liver of obese mice. Celastrol influenced the gene expression of galanin receptors: it downregulated Galr1 in the heart and upregulated Galr2 in the liver and Galr3 in the heart ventricles, potentially affecting energy metabolism, oxidative stress, and inflammation. Fatostatin suppressed gene expression of all the detected members of the galaninergic system in the heart ventricles, depicting the role of SREBP in this process. Conclusion: These findings suggest that celastrol may beneficially modulate the galaninergic system under obesity and MASLD-to-MASH progression, indicating its potential as a therapeutic agent for disorders associated with metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Perivascular adipose tissue (PVAT) regulates vascular tone and is composed of adipocytes and several leukocyte subpopulations. Diet can modify PVAT function, as obesogenic diets cause morphological changes to adipocytes and skew the leukocyte phenotype, leading to PVAT dysregulation and impaired vasoregulation. Of note, platelets, the clot-forming cells, also modulate many facets of leukocyte activity, such as tissue infiltration and polarity. We aimed to determine whether platelets regulate the leukocyte populations residing within PVAT. Male C57Bl/6J mice were fed a Western diet (30% kcal sucrose, 40% kcal fat, 8.0% sodium) to develop obesogenic conditions for PVAT leukocyte remodeling. Diet was either administered acutely (2 weeks) or extended (8 weeks) to gauge the length of challenge necessary for remodeling. Additionally, platelet depletion allowed for the assessment of platelet relevance in PVAT leukocyte remodeling. Abdominal PVAT (aPVAT) and thoracic PVAT (tPVAT) were then isolated and leukocyte composition evaluated by flow cytometry. Compared to control, Western diet alone did not significantly impact PVAT leukocyte composition for either diet length. Platelet depletion, independent of diet, significantly disrupted PVAT leukocyte content with monocytes/macrophages most impacted. Furthermore, tPVAT appeared more sensitive to platelet depletion than aPVAT, providing novel evidence of platelet regulation of leukocyte composition within PVAT depots. [ABSTRACT FROM AUTHOR]

Nutritional status disorders have the most significant impact on the development of cardiovascular and oncologic diseases; therefore, the interest in the study of palm oil as among the leading components of nutrition has been increasing. The data examined in this review were sourced from the Scopus, SCIE (Web of Science), PubMed and PubMed Central, MEDLINE, CAPlus/SciFinder, and Embase databases; experts in the field; bibliographies; and abstracts from review analyses from the past 15 years. This review summarizes recent research data focusing on the quantitative and qualitative composition of nutrition of modern humans; concepts of the relationship between high-fat diets and disorders of insulin functioning and transport and metabolism of fatty acids; analyses of data regarding the palmitic acid (16:0) to oleic acid (18:1) ratio; and the effect of diet based on palm oil consumption on cardiovascular risk factors and lipid and lipoprotein levels. Several studies suggest a potential vector contributing to the transmission of maternal, high-fat-diet-induced, addictive-like behaviors and obesogenic phenotypes across generations. The relationship between cholesterol accumulation in lysosomes that may lead to lysosome dysfunction and inhibition of the autophagy process is analyzed, as is the progression of inflammatory diseases, atherosclerosis, nonalcoholic liver inflammation, and obesity with associated complications. Data are discussed from analyses of differences between rodent models and human population studies in the investigated different effects of palm oil consumption as a high-fat diet component. A conclusion is reached that the results cannot be generalized in human population studies because no similar effects were observed. Although there are numerous published reports, more studies are necessary to elucidate the complex regulatory mechanisms in digestive and nutrition processes, because there are great differences in lipoprotein profiles between rodents and humans, which makes it difficult to reproduce the pathology of many diseases caused by different types of the high-fat diet. [ABSTRACT FROM AUTHOR]

Western dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8 weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases. [ABSTRACT FROM AUTHOR]

Recent findings reveal the importance of tryptophan-initiated de novo nicotinamide adenine dinucleotide (NAD+) synthesis in the liver, a process previously considered secondary to biosynthesis from nicotinamide. The enzyme α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), primarily expressed in the liver and kidney, acts as a modulator of de novo NAD+ synthesis. Boosting NAD+ levels has previously demonstrated remarkable metabolic benefits in mouse models. In this study, we aimed to investigate the therapeutic implications of ACMSD inhibition in the treatment of metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH). In vitro experiments were conducted in primary rodent hepatocytes, Huh7 human liver carcinoma cells and induced pluripotent stem cell-derived human liver organoids (HLOs). C57BL/6J male mice were fed a western-style diet and housed at thermoneutrality to recapitulate key aspects of MASLD/MASH. Pharmacological ACMSD inhibition was given therapeutically, following disease onset. HLO models of steatohepatitis were used to assess the DNA damage responses to ACMSD inhibition in human contexts. Inhibiting ACMSD with a novel specific pharmacological inhibitor promotes de novo NAD+ synthesis and reduces DNA damage ex vivo , in vivo, and in HLO models. In mouse models of MASLD/MASH, de novo NAD+ biosynthesis is suppressed, and transcriptomic DNA damage signatures correlate with disease severity; in humans, Mendelian randomization-based genetic analysis suggests a notable impact of genomic stress on liver disease susceptibility. Therapeutic inhibition of ACMSD in mice increases liver NAD+ and reverses MASLD/MASH, mitigating fibrosis, inflammation, and DNA damage, as observed in HLO models of steatohepatitis. Our findings highlight the benefits of ACMSD inhibition in enhancing hepatic NAD+ levels and enabling genomic protection, underscoring its therapeutic potential in MASLD/MASH. Enhancing NAD+ levels has been shown to induce remarkable health benefits in mouse models of metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH), yet liver-specific NAD+ boosting strategies remain underexplored. Here, we present a novel pharmacological approach to enhance de novo synthesis of NAD+ in the liver by inhibiting α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), an enzyme highly expressed in the liver. Inhibiting ACMSD increases NAD+ levels, enhances mitochondrial respiration, and maintains genomic stability in hepatocytes ex vivo and in vivo. These molecular benefits prevent disease progression in both mouse and human liver organoid models of steatohepatitis. Our preclinical study identifies ACMSD as a promising target for MASLD/MASH management and lays the groundwork for developing ACMSD inhibitors as a clinical treatment. [Display omitted] • ACMSD inhibition enhances NAD+ de novo synthesis and enables genome stability in hepatocytes. • ACMSD inhibition increases NAD+ levels, reduces DNA damage and prevents MASLD/MASH progression. • The therapeutic benefits of ACMSD inhibition are recapitulated in human liver organoid models of steatohepatitis. • Mendelian randomization suggests causality of DNA damage in MASLD/MASH incidence. [ABSTRACT FROM AUTHOR]

Dietary patterns, such as the Mediterranean diet (MD) and the Western diet (WD), influence gut microbiota composition and functionality, which play important roles in energy metabolism and nutrient absorption. Objectives: A descriptive cross-sectional study was designed to evaluate the gut microbiota of 19 Spanish adolescents and to investigate the association of MD and ultra-processed food (UPF) intake with microbial diversity and community structure. Methods: Functional diversity of gut microbiota was evaluated using Biolog EcoPlates, taxonomic composition was assessed with 16S rRNA sequencing via MinION, and phenotypic responses to antibiotics were analyzed using the cenoantibiogram technique under aerobic and anaerobic conditions. Results: Adolescents with higher adherence to the MD exhibited greater functional diversity, as per the Shannon–Weaver index. In addition, this group showed higher abundance of bacterial genera previously described as beneficial, such as Paraclostridium, Anaerobutyricum, Romboutsia, and Butyricicoccus. In contrast, adolescents reporting greater UPF intakes had a microbiota composition similar to those with low adherence to the MD, characterized by decreased abundance of beneficial genera. Regarding antibiotic resistance, significant differences were only observed under anaerobic conditions, with individuals with low adherence to the MD showing more sensitivity for most antibiotics tested. Conclusions: These results suggest that the MD promotes a healthier and more balanced gut environment, potentially improving metabolic functions in adolescents. Despite the lack of differences in α-diversity, comparisons of microbial community structure between adolescents following the MD and those with high UPF (characteristic of the WD) showed clear differences in terms of β-diversity. These findings suggest that dietary patterns influence the composition of the gut microbiota in a more complex manner, beyond just taxonomic richness. The outcomes of this exploratory study highlight opportunities for future research to deepen understanding of the long-term health implications of these dietary patterns, as well as the mechanisms regulating the composition, functionality, and phenotypic responses to antibiotics of gut microbial communities. [ABSTRACT FROM AUTHOR]

Background: MetaDAG is a web-based tool developed to address challenges posed by big data from omics technologies, particularly in metabolic network reconstruction and analysis. The tool is capable of constructing metabolic networks for specific organisms, sets of organisms, reactions, enzymes, or KEGG Orthology (KO) identifiers. By retrieving data from the KEGG database, MetaDAG helps users visualize and analyze complex metabolic interactions efficiently. Results: MetaDAG computes two models: a reaction graph and a metabolic directed acyclic graph (m-DAG). The reaction graph represents reactions as nodes and metabolite flow between them as edges. The m-DAG simplifies the reaction graph by collapsing strongly connected components, significantly reducing the number of nodes while maintaining connectivity. MetaDAG can generate metabolic networks from various inputs, including KEGG organisms or custom data (e.g., reactions, enzymes, KOs). The tool displays these models on an interactive web page and provides downloadable files, including network visualizations. MetaDAG was tested using two datasets. In an eukaryotic analysis, it successfully classified organisms from the KEGG database at the kingdom and phylum levels. In a microbiome study, MetaDAG accurately distinguished between Western and Korean diets and categorized individuals by weight loss outcomes based on dietary interventions. Conclusion: MetaDAG offers an effective and versatile solution for metabolic network reconstruction from diverse data sources, enabling large-scale biological comparisons. Its ability to generate synthetic metabolisms and its broad application, from taxonomy classification to diet analysis, make it a valuable tool for biological research. MetaDAG is available online, with user support provided via a comprehensive guide. MetaDAG: https://bioinfo.uib.es/metadag/ User guide: https://biocom-uib.github.io/MetaDag/ [ABSTRACT FROM AUTHOR]

Female infertility is a multifactorial condition influenced by various genetic, environmental, and lifestyle factors. Recent research has investigated the significant impact of gut microbiome dysbiosis on systemic inflammation, metabolic dysfunction, and hormonal imbalances, which can potentially impair fertility. The gut-brain axis, a bidirectional communication system between the gut and the brain, also plays a significant role in regulating reproductive functions. Emerging evidence suggests that the gut microbiome can influence brain functions and behavior, further emphasizing the importance of the microbiota-gut-brain axis in reproduction. Given their role as a major modulator of the gut microbiome, diet and dietary factors, including dietary patterns and nutrient intake, have been implicated in the development and management of female infertility. Hence, this review aims to highlight the impact of dietary patterns, such as the Western diet (WD) and Mediterranean diet (MD), and to decipher their modulatory action on the microbiota-gut-brain axis in infertile women. By contrasting the detrimental effects of WD with the therapeutic potential of MD, we emphasize the pivotal role of a balanced diet rich in nutrients in promoting a healthy gut microbiome. These insights underscore the potential of targeted dietary interventions and lifestyle modifications as promising strategies to enhance reproductive outcomes in subfertile women. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic condition influenced by diet, which affects gut microbiota and immune functions. The rising prevalence of IBD, linked to Western diets in developing countries, highlights the need for dietary interventions. This study aimed to assess the impact of white kidney beans (WKB) on gut inflammation and microbiota changes, focusing on their effects on enteric glial cells (EGCs) and immune activity in colitis. Methods: Male C57BL/6 mice were divided into four groups: normal diet (ND), ND with 2.5% dextran sulfate sodium (DSS) for colitis induction, ND with 20% WKB, and WKB with 2.5% DSS. The dietary intervention lasted 17 weeks, with DSS given in the final week. Colonic inflammation was assessed by body weight, disease activity index, and histopathology. Epithelial barrier integrity was evaluated using immunofluorescence, transmission electron microscopy, and permeability assays. EGCs activity was analyzed via immunofluorescence and quantitative real-time PCR. Immune responses were measured using flow cytometry and cytokine profiling, while gut microbiota changes were examined through metagenomic sequencing. Results: WKB supplementation significantly alleviated DSS-induced colitis in mice, evidenced by reduced weight loss, disease activity, and improved colonic histology. This effect was linked to enhanced mucosal barrier integrity, seen through increased tight junction protein and Muc2 expression, accompanied by favorable ultrastructural changes. WKB modulated EGCs activity via TNF-like cytokine 1 A inhibition, resulting in reduced glial fibrillary acidic protein expression. Immunologically, it downregulated Th1 and Th17 pro-inflammatory cells, increased Treg cells, and altered cytokine profiles (reduced TNF-α, IFN-γ, IL-17; increased IL-10). Metagenomic analysis showed that WKB restored gut microbiota balance, particularly enhancing beneficial bacteria like Akkermansia. KEGG pathway analysis further indicated that WKB supplementation improved key metabolic pathways, notably those related to phenylalanine, tyrosine, and tryptophan biosynthesis, thereby countering DSS-induced metabolic disruptions. Conclusions: WKB shows promise for treating IBD by enhancing mucosal barriers, inhibiting EGCs activity, balancing Th1/Th17/Treg cells, and restoring gut microbiota and metabolic homeostasis, thereby alleviating colitis symptoms. [ABSTRACT FROM AUTHOR]

Objective To study the protective effect of melatonin on PM2.5-induced inflammation and lymphangiogenesis in the lung of ApoE-/- mice. Methods Twenty-eight male ApoE-/- mice were randomized into # control group, PM2.5 group, melatonin group and PM2.5 + melatonin group. All mice were fed with western diet for 24 weeks. From the 25th week, mice in the melatonin group and PM2.5 + melatonin group were daily orally gavage with melatonin (20 mg/kg • bw) for 8 weeks; mice in the PM2.5 group and PM2.5 + melatonin group were exposed to PM2.5 by tracheal instillation (5mg/kg); and mice in the control group and melatonin group were instilled with saline at the same time. After 24 h of PM2.5 exposure, mice were euthanized and weight gain and lung weight/body weight ratio in four groups were analyzed. The concentrations of inflammatory cytokines (TNF - α and IL-6) in the lung tissue of mice were measured. Immunofluorescence staining of lung tissue was visualized the lymphatic marker LYVE1 expression. Western Blot was used to assess the protein expression levels of lymphangiogenesis markers PROX1 and LYVE1, lymphangiogenesis regulatory proteins VEGF-C and VEGFR-3 in lung tissues. Results The levels of TNF-α and IL-6 and the protein expressions of PROX1, LYVE1, VEGF-C and VEGFR-3 in lung tissues of PM2.5 group were significantly higher than the control group (P < 0.05). Moreover, the levels of TNF-α, IL-6 and the protein expressions of PROX1, LYVE1, VEGF-C and VEGFR-3 in lung tissues of the PM2.5 + melatonin group were significantly lower than the PM2.5 group (P < 0.05). Conclusion Ambient PM2. 5 exposure obviously increases lung inflammation of ApoE-/- mice, and may increase lymphangiogenesis in lung through regulating the VEGF-C/VEGFR-3 signaling pathway in the lung tissues; melatonin markedly improves PM2.5-induced lung inflammation and reduces lymphangiogenesis in lung. [ABSTRACT FROM AUTHOR]

As global temperatures rise, heat-related chronic health disorders are predicted to become more prevalent. We tested whether a single exposure to acute heat illness, using a preclinical mouse model of exertional heat stroke (EHS), can induce late-emerging health disorders that progress into chronic disease. Following EHS, mice were followed for 3 months; after two weeks of recovery, half were placed on a Western diet to determine if previous EHS exposure amplifies the negative consequences of an atherogenic diet. When compared to sham exercise controls, EHS-exposed mice exhibit accelerated diet-induced obesity, develop low level cardiac hypertrophy, develop accelerated diet-induced liver steatosis, severe hypoproteinemia and a loss of metabolic flexibility in the myocardium. The latter is characterized by a shift towards predominant glucose metabolism and glycolysis. These results demonstrate that a single exposure to severe exertional heat illness can induce long-lasting and unexpected health consequences in mammals and increased vulnerability to secondary metabolic stressors. Exposure to elevated temperatures can result in adverse health conditions; in this study, a single bout of exertional heat stroke was found to accelerate diet-induced obesity and cardiac hypertrophy, and to diminish metabolic flexibility in mouse cardiac tissue. [ABSTRACT FROM AUTHOR]

Competition among bacteria for carbohydrates is pivotal for colonization resistance (CR). However, the impact of Western-style diets on CR remains unclear. Here we show how the competition between Klebsiella oxytoca and Klebsiella pneumoniae is modulated by consuming one of three Western-style diets characterized by high-starch, high-sucrose, or high-fat/high-sucrose content. In vivo competition experiments in ampicillin-treated mice reveal that K. oxytoca promotes K. pneumoniae decolonization on all dietary backgrounds. However, mice on the high-fat/high-sucrose diet show reduced pathogen clearance. Microbiome analysis reveals that the combination of Western-style diets and ampicillin treatment synergize in microbiome impairment, particularly noticeable in the presence of high dietary fat content. The diet-independent degradation of ampicillin in the gut lumen by K. oxytoca beta-lactamases facilitates rapid commensal outgrowth, which is required for subsequent pathogen clearance. Our findings provide insights into how diet modulates functional microbiome recovery and K. oxytoca-mediated pathogen elimination from the gut. The authors demonstrate in a mouse model that Western-style diets synergize with antibiotics to impair microbiota function. In turn, Klebsiella oxytoca promotes post-antibiotic microbiota recovery and removal of the pathogen Klebsiella pneumoniae. [ABSTRACT FROM AUTHOR]

Aristolochic acid (AA) ingestion causes Balkan nephropathy, characterized by tubular injury and progression to chronic kidney disease (CKD). AA is taken up by proximal tubule cells via organic anion transport and induces p21-mediated DNA damage response, but little is known about dietary modulating factors. Western diet (WD) is rich in saturated fats and sugars and can promote metabolic disorders and CKD progression. Here, we determined the impact of WD on AA-induced kidney injury. Five-week-old male C57BL/6J mice were fed WD or normal chow (NC) for 8 wk, followed by administration of AA every 3 days for 3 wk. Measurements were performed after the last injection and following a 3-wk recovery. Independent of dosing AA by body weight (3 mg/kg/day) or same dose/mouse (0.1125 mg/day), the AA-induced increase in plasma creatinine and reduction of hematocrit were greater in WD versus NC. This was associated with increased kidney gene expression in WD vs. NC of markers of DNA damage (p21), injury (Kim1 and Ngal), and inflammation (Tnfa) and kidney fibrosis staining. WD alone increased fractional excretion of indoxyl sulfate by 7.5-fold, indicating enhanced kidney organic anion transport. Kidney proteomics identified further WD-induced changes that could increase kidney sensitivity to AA and contribute to the altered response to AA including weakening of energy metabolism, potentiation of immune and infection pathways, and disruption in RNA regulation. In conclusion, WD can increase the susceptibility of mice to Balkan nephropathy, possibly in part through facilitating kidney uptake of the organic anion AA. NEW & NOTEWORTHY: This study shows that a Western diet (WD) aggravates a murine model of Balkan nephropathy induced by the application of the organic anion and nephrotoxin aristolochic acid (AA). Mechanistically, this may involve WD-induced kidney organic anion secretion, which can facilitate the AA uptake into proximal tubular cells and thereby contribute to the injury. Kidney proteomics identified further changes induced by feeding a WD that could have increased the sensitivity of the kidney to stress and injury. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a prevalent aging disorder of synovial joints and recent work suggests that a parental high‐fat diet increases OA severity following joint injury in offspring. We hypothesized that a maternal high‐fat high‐sugar (HFHS) diet would promote spontaneous osteoarthritis‐related cartilage and bone changes in 1‐year‐old offspring. Female C57BL/6 J mice were placed on either a chow control or HFHS diet for 6 weeks before mating to a chow‐fed C57BL/6 J male and maintained on their assigned diets throughout pregnancy and lactation. Male and female offspring were weaned onto a chow diet, raised to 1 year of age, and evaluated for cartilage and bone changes indicative of OA. However, offspring did not show early signs of OA as measured by histological Mankin scoring, mechanical testing of the pericellular matrix, histological synovitis scoring, or subchondral bone thickening as measured by microcomputed Tomography. On the other hand, male offspring from HFHS‐fed dams had reduced trabecular bone quality in the tibial metaphysis and decreased cortical thickness. Although maternal HFHS diet did not impact trabecular or cortical bone quality in tibias of female offspring, the radii of these animals had decreased cortical thickness, increased medullary area, and impaired breaking strength compared to those of control‐fed dams. Finally, we evaluated bone quality and strength in male and female F2 offspring and found that the grandmaternal diet modestly impacted radial bone geometry but not strength. Together these results suggest that maternal HFHS diet impairs F1 offspring skeletal integrity in a sex and bone site‐specific manner. [ABSTRACT FROM AUTHOR]

Background: Black adults have a higher risk for heart failure (HF) than others, which may be related to higher cardiovascular risk factors and also inflammatory dietary patterns. The Western diet is associated with inflammation and contributes to HF. Trimethylamine N -oxide is a diet-linked metabolite that contributes to inflammation and is associated with higher tumor necrosis factor-alpha (TNF-α) levels, especially in HF populations. The dietary inflammatory index score measures a diet's inflammatory potential and food's inflammatory effects. Objective: The purpose of this pilot study was to explore associations between the Western diet, dietary inflammatory index, trimethylamine N -oxide, relevant covariates and variables, and TNF-α in Black persons with HF. Methods: Thirty-one Black participants (mean age = 55 years, 68% women) with HF were enrolled. Trimethylamine N -oxide and TNF-α levels were analyzed using immunoassays. A food frequency questionnaire was completed, and dietary inflammatory index scores and food groups were calculated. Analyses included correlations and I -test statistics. Results: Mean dietary inflammatory index score was −0.38, noting an anti-inflammatory diet with slightly higher inflammatory diet scores in men compared to women. The dietary inflammatory index score showed a negative association with dietary choline but not with trimethylamine N -oxide or TNF-α. Trimethylamine N -oxide and age were positively correlated, along with the correlation for TNF-α with a moderate effect size. No relationship was found among dietary inflammatory index, TNF-α, and trimethylamine N -oxide variables. Discussion: A greater understanding of intake of inflammatory foods and relationships with immune factors is warranted to inform intervention development. In Black adults with HF, it is important to consider the intake of inflammatory foods as increased age may affect the retention of dietary metabolites. Metabolites may also increase the levels of inflammation. Knowledge about these relationships could lead to tailored dietary interventions based on diet, age, and culture patterns. [ABSTRACT FROM AUTHOR]

Aims: Our goal is to perform a meta-analysis to investigate the risk of periodontitis associated with specific dietary patterns. Methods: We employed the PRISMA methodology in a meta-analysis to examine the correlation between dietary patterns and the risk of periodontitis. We systematically searched three online databases from inception to November 2024 to identify relevant studies. Summary estimates with 95%CI were calculated to assess the relationship between specific dietary patterns and the risk of periodontitis. Cumulative estimates were synthesized using random-effects or fixed-effects models. Heterogeneity among studies was evaluated using Cochran’s Q and I2 statistics. Results: In total, we included 19 articles that analyzed 5 dietary patterns The study showed that a diet high in inflammation-promoting foods significantly raised the likelihood of periodontitis (OR = 1.39, 95% CI, 1.09–1.77), in contrast, dietary patterns like the mediterranean diet (OR = 0.96, 95% CI, 0.94–0.98), plant-based diet (OR = 0.92, 95% CI, 0.86–0.98), or dairy-rich diet (OR = 0.76, 95% CI, 0.66–0.87) lowered the risk of periodontitis. The analysis revealed no statistically significant association between a western diet (OR = 1.07; 95% CI, 0.86–1.33) and the risk of periodontitis. Conclusions: As dietary diversity and complexity continue to expand, there has been a concomitant increase in the prevalence of periodontal disease. This study has identified specific dietary patterns associated with the risk of periodontitis, particularly highlighting the heightened risk linked to pro-inflammatory diets. These findings emphasize the importance of implementing targeted dietary practices to reduce the incidence of this condition. [ABSTRACT FROM AUTHOR]

Aim: Increasing the dietary intake of K+ in the setting of a high salt intake promotes renal Na+ excretion even though K+ concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na+ reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na+ reabsorption after high K+ intake. Methods: Mice were fed diets containing varying amounts of Na+ combined with KCl or KCitrate. Murine cortical connecting duct (mCCDcl1) cells were cultured in media containing normal or high [Cl−]. The response to aldosterone was analyzed by high‐resolution imaging and by biochemical approaches. Results: The canonical cellular response to aldosterone, encompassing translocation of the mineralocorticoid receptor (MR) and activation of the epithelial Na+ channel ENaC was repressed in Na+‐replete mice fed a high KCl diet, even though plasma aldosterone concentrations were increased. The response to aldosterone was restored in Na+‐replete mice when the extracellular [Cl−] increase was prevented by feeding a high KCitrate diet. In mCCDcl1 cells, an elevated extracellular [Cl−] was sufficient to disrupt the aldosterone‐induced MR translocation. Conclusion: These findings indicate a pivotal role for extracellular [Cl−] in modulating renal aldosterone signaling to adapt MR activation by a high K+ intake to the NaCl balance. An impairment of [Cl−]‐mediated aldosterone resistance may contribute to excessive MR activation by aldosterone in the presence of a high salt intake characteristic of the Western diet, resulting in an inappropriate salt reabsorption and its downstream detrimental effects. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet and exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, the ketogenic diet, intermittent fasting, and high fiber diets have demonstrated potential in addressing the metabolic dysfunction underlying this condition. The development and progression of MASLD are closely associated with taxonomic shifts in gut microbial communities, a relationship well-documented in the literature. Given the importance of diet as a primary treatment for MASLD, it is important to understand how gut microbiota and their metabolic byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, microbiota changes conferred by unhealthy dietary patterns such as the Western diet may induce dysbiosis and influence steatotic liver disease through promoting hepatic inflammation, up-regulating lipogenesis, dysregulating bile acid metabolism, increasing insulin resistance, and causing oxidative damage in hepatocytes. Although emerging evidence has identified links between diet, microbiota, and development of MASLD, significant gaps remain in understanding specific microbial roles, metabolite pathways, host interactions, and causal relationships. Therefore, this review aims to provide mechanistic insights into the role of microbiota-mediated processes through the analysis of both healthy and unhealthy dietary patterns and their contribution to MASLD pathophysiology. By better elucidating the interplay between dietary nutrients, microbiota-mediated processes, and the onset and progression of steatotic liver disease, this work aims to identify new opportunities for targeted dietary interventions to treat MASLD efficiently. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome poses a significant public health challenge globally, particularly among older adults. Dietary patterns play a crucial role in the development and management of metabolic syndrome. However, to our knowledge, no evidence exists regarding the association between dietary patterns and metabolic syndrome among the Mexican older adult population. Thus, the objective of the present study is to assess the association between dietary patterns and metabolic syndrome in Mexican older adults. Methods: This cross-sectional study utilized data from the Mexican National Health and Nutrition Survey 2016 to investigate the relationship between dietary patterns and metabolic syndrome in 804 OA (aged ≥60 years). Dietary patterns were derived using factor analysis, and metabolic syndrome was defined based on established criteria. Logistic regression models were employed to assess associations, adjusting for potential confounders. Results: Three dietary patterns were identified: a "Westernized" pattern characterized by high consumption of processed meat, red meat, and saturated fats; a "Transitional" pattern high in fresh vegetables and fruits; and a "Prudent" pattern high in fish and low-fat dairy products. The "Westernized" pattern exhibited a positive association with metabolic syndrome, while the "Prudent" pattern showed a negative association. The associations remained significant after adjusting for confounders. Biological mechanisms linking the "Westernized" pattern to metabolic syndrome include chronic inflammation, endothelial dysfunction, and dyslipidemia induced by components such as processed meats and soft drinks. Conclusion: Our study highlights the importance of dietary patterns in influencing metabolic syndrome risk among Mexican older adults. Promoting dietary patterns rich in fish, vegetables, and legumes while reducing consumption of processed meats and sugary beverages may offer significant health benefits in this population. Further prospective studies are needed to confirm these findings and inform targeted interventions for metabolic syndrome prevention and management in older adults. [ABSTRACT FROM AUTHOR]

Isabelle Gallagher,1 Yanrong Li,1 Cherry Youn,1 Hirofumi Tanaka,2 Jaimie N Davis,3 Andreana P Haley1 1Department of Psychology, University of Texas at Austin, Austin, TX, USA; 2Cardiovascular Aging Research Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX, USA; 3Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USACorrespondence: Andreana P Haley, Department of Psychology, The University of Texas at Austin, SEA 3.130E, 108 E Dean Keeton St, Austin, TX, 78712, USA, Tel +1 512 232 0863, Fax +1 512 471-6175, Email haley@austin.utexas.eduPurpose: With Alzheimer’s disease and related dementias are projected to triple by 2050, addressing modifiable health and lifestyle factors is crucial to prevention and reducing the associated public health burden. This study investigates the interaction between triglyceride levels and dietary fat intake and diet quality on memory performance in middle-aged adults at heightened risk for metabolic health issues.Patients and Methods: Community-dwelling adults aged 40– 65 with cardiometabolic health risks participated in this cross-sectional study. Participants with a history of neurological or psychiatric conditions were excluded. Dietary intake was self-reported through a 3-day food record, and serum triglyceride levels were measured. Neuropsychological testing assessed memory performance. Cross-sectional regression analyses examined how dietary fat intake and quality interact with triglyceride levels to affect memory performance in 146 adults.Results: The analysis revealed a significant interaction between triglyceride levels and the ratio of dietary saturated fat to total caloric intake on memory performance (β = − 0.087, p = 0.022). The relationship between triglyceride levels and memory performance was modified by the ratio of saturated fat to total caloric intake. At higher levels of saturated fat intake, higher triglycerides were associated with worse memory performance. However, at lower levels of saturated fat intake, the association between triglycerides and memory performance was not statistically significant. Better adherence to USDA dietary guidelines, reflected by higher Healthy Eating Index 2020 scores, was associated with better memory performance (β = 0.018, p < 0.002), regardless of triglyceride levels.Conclusion: Diet quality, as indicated by adherence to dietary guidelines, supports cognitive health. Elevated triglycerides combined with a high ratio of dietary saturated fat intake were associated with poorer memory performance. Precision nutrition strategies aimed at reducing saturated fat intake in midlife adults with elevated triglyceride levels may help mitigate memory-related cognitive decline and enhance brain health.Plain Language Summary: This study explored how diet and triglyceride levels (a type of fat in the blood) might influence memory and the risk of Alzheimer’s disease and other dementias in adults at higher risk. We focused on middle-aged adults (ages 40-65) who had cardiometabolic health issues, such as obesity, high blood pressure, high cholesterol, or diabetes. We worked with 146 adults from the community who reported their eating habits over three days and took tests to measure triglyceride levels and memory performance. The study found that higher triglyceride levels combined with a diet high in saturated fats (common in many Western diets) were linked to poorer memory performance. However, adults with high triglycerides who ate less saturated fat performed better on memory tests than those with higher saturated fat intake. Overall, following a healthier diet was associated with better memory, regardless of triglyceride levels. These findings suggest that improving diet quality—by adhering to dietary guidelines—could help protect brain health and reduce memory problems. For people with high triglycerides, cutting back on saturated fat may help improve memory and protect against cognitive decline. These results point to the importance of personalized nutrition strategies to support brain health and potentially reduce the risk of memory loss as we age.Keywords: cardiometabolic, Western diet, cognition, midlife

Abstract Background Long-term consumption of Western Diet (WD) is a well-established risk factor for the development of cardiovascular disease (CVD); however, there is a paucity of studies on the long-term effects of WD on the pathophysiology of CVD and sex-specific responses. Methods Our study aimed to investigate the sex-specific pathophysiological changes in left ventricular (LV) function using transthoracic echocardiography (ECHO) and LV tissue transcriptomics in WD-fed C57BL/6 J mice for 125 days, starting at the age of 300 through 425 days. Results In female mice, consumption of the WD diet showed long-term effects on LV structure and possible development of HFpEF-like phenotype with compensatory cardiac structural changes later in life. In male mice, ECHO revealed the development of an HFrEF-like phenotype later in life without detectable structural alterations. The transcriptomic profile revealed a sex-associated dichotomy in LV structure and function. Specifically, at 530-day, WD-fed male mice exhibited differentially expressed genes (DEGs), which were overrepresented in pathways associated with endocrine function, signal transduction, and cardiomyopathies. At 750 days, WD-fed male mice exhibited dysregulation of several genes involved in various lipid, glucagon, and glutathione metabolic pathways. At 530 days, WD-fed female mice exhibited the most distinctive set of DEGs with an abundance of genes related to circadian rhythms. At 640 days, altered DEGs in WD-fed female mice were associated with cardiac energy metabolism and remodeling. Conclusions Our study demonstrated distinct sex-specific and age-associated differences in cardiac structure, function, and transcriptome signature between WD-fed male and female mice. Graphical Abstract

Clinical studies strongly suggest the importance of diet quality on cognition in youth populations (15–24 years). The Mediterranean diet (MeDi) has been shown to improve cognition in contrast to the commonly consumed Western diet (WD). The gut microbiota may serve as a mechanism for diet-induced changes in cognition. Ten-week-old male Sprague Dawley rats were assigned a MeDi or WD (n = 10/group) for 14 weeks. Prior to neurobehavior assessments, microbiota community composition was assessed. At the genus level, the relative abundance of four bacteria increased with the MeDi and five decreased compared to the WD. Rats in the MeDi group demonstrated cognitive flexibility and improvement in reference and working memory relative to the WD group. At the end of the study, serum cytokines were increased, and low-density lipoproteins were decreased in the MeDi group. Markers for neuroinflammation, blood-brain barrier, glial cells, and synaptic plasticity in brain regions did not differ between groups. Overall, the MeDi modulated gut microbiota, cognitive function, and serum lipid and cytokines but not gene expression in the brain compared to the WD. Further studies are needed to determine causality between diet-modulated gut microbiota, cognitive function, and immune function.

Abstract Background Premature coronary artery disease (PCAD) is one of the major health concerns leading to considerable death and disabilities. This study aimed to evaluate the relationship of dietary patterns with risk of PCAD. Methods Iran premature coronary diseases (IPAD) is a case-control study consists of 3159 participants. Obstructive CAD in ≥ 75% of at least one coronary artery or ≥ 50% in the left main artery based on coronary angiography in women under 70 and men under 60 years old was considered PCAD. The habitual dietary intake of participants was collected using a semi-quantitative validated food frequency questionnaire (SFFQ). Principal Component Analysis (PCA) was used to extract dietary patterns. Results Three main dietary patterns including healthy, Western and high-fat, high-sugar were identified. Patients categorized in the last tertile of the healthy dietary pattern had a decreased risk of PCAD (OR = 0.77, 95% CI: 0.64–0.93), while those in the top tertile of Western (OR = 2.38, 95 CI:1.97–2.86) and High-fat simple carbohydrate (HFSC) (OR = 3.10, 95% CI:2.57–3.75) diets had increased risk of PCAD. Conclusions A healthy dietary pattern was significantly related to a decreased risk of PCAD presence, whereas Western and HFSC diets were connected to a higher risk of PCAD.

Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. We did not observe significant changes in either biochemical parameters or levels of circulating markers of inflammation across the entire cohort. However, paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance of Weizmannia, a kombucha-enriched probiotic and several SCFA producing taxa to be overrepresented in consumers at the end of the intervention. Collectively, in our healthy cohort consuming a Western diet, a short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters, which may be attributed to relatively small number of participants and the extensive inter-participant variability. [ABSTRACT FROM AUTHOR]

Background: Long-term consumption of Western Diet (WD) is a well-established risk factor for the development of cardiovascular disease (CVD); however, there is a paucity of studies on the long-term effects of WD on the pathophysiology of CVD and sex-specific responses. Methods: Our study aimed to investigate the sex-specific pathophysiological changes in left ventricular (LV) function using transthoracic echocardiography (ECHO) and LV tissue transcriptomics in WD-fed C57BL/6 J mice for 125 days, starting at the age of 300 through 425 days. Results: In female mice, consumption of the WD diet showed long-term effects on LV structure and possible development of HFpEF-like phenotype with compensatory cardiac structural changes later in life. In male mice, ECHO revealed the development of an HFrEF-like phenotype later in life without detectable structural alterations. The transcriptomic profile revealed a sex-associated dichotomy in LV structure and function. Specifically, at 530-day, WD-fed male mice exhibited differentially expressed genes (DEGs), which were overrepresented in pathways associated with endocrine function, signal transduction, and cardiomyopathies. At 750 days, WD-fed male mice exhibited dysregulation of several genes involved in various lipid, glucagon, and glutathione metabolic pathways. At 530 days, WD-fed female mice exhibited the most distinctive set of DEGs with an abundance of genes related to circadian rhythms. At 640 days, altered DEGs in WD-fed female mice were associated with cardiac energy metabolism and remodeling. Conclusions: Our study demonstrated distinct sex-specific and age-associated differences in cardiac structure, function, and transcriptome signature between WD-fed male and female mice. [ABSTRACT FROM AUTHOR]

The scarcity of donors has prompted the growing utilization of steatotic livers, which are susceptible to injuries following orthotopic liver transplantation (OLT). This study aims to assess the efficacy of multidrug donor preconditioning (MDDP) in alleviating injuries of steatotic grafts following rat OLT. Lean rats were subjected to a Western-style diet with high-fat (HF) and high-fructose (HFr) for 30 days to induce steatosis. Both lean and steatotic livers were implanted into lean recipients fed with a chow diet after OLT. The HF + HFr diet effectively elevated blood triglyceride and cholesterol levels and induced fat accumulation in rat livers. Our results demonstrated a significant decrease in alanine aminotransferase levels (p = 0.003), aspartate aminotransferase levels (p = 0.021), and hepatic Suzuki scores (p = 0.045) in the steatotic rat liver allograft group following MDDP treatment on post-operation day (POD) 7. Furthermore, the survival rates of steatotic rat liver allografts with MDDP (19/21, 90.5%) were significantly higher than those in the steatotic control (12/21, 57.1%, * p = 0.019). These findings indicate that MDDP treatment improves steatotic rat liver allograft function and recipient survival following OLT. [ABSTRACT FROM AUTHOR]

Background and objectives: Maternal western-style diets that are high in glucose and fat have well-known cardiovascular effects on offspring, yet the combined influence of such diets during pregnancy is relatively less comprehended. This study investigates the impact of maternal high glucose and fat diet (HGF) on vascular constriction in offspring and the underlying mechanisms. Methods and results: Pregnant Sprague–Dawley rats were provided with either HGF or control diets. The assessment of fetal and postnatal vascular function disclosed an enhanced sensitivity to angiotensin II-induced vascular constriction in the offspring exposed to HGF. This was ascribed to increased oxidative stress via upregulated NOX2 expression, which was due to downregulated SHIP2 expression that was influenced by upregulated miR-325-3p. The maternal HGF diet elevated miR-325-3p, suppressed SHIP2 and enhanced NOX2 expression in fetal vascular tissues, thereby resulting in vascular dysfunction. These alterations persist into adulthood, heightening the risk of vascular diseases. Conclusion: The present study is the first to demonstrate that maternal HGF diet impairs vascular constriction function in offspring through the miR-325-3p/SHIP2/NOX2 pathway. These novel findings indicate that the detrimental effects of maternal HGF diet on fetal vascular function can persist into adulthood, advancing our knowledge on the impact of maternal diet on offspring vascular health and the early stages of fetal-origin vascular diseases. [ABSTRACT FROM AUTHOR]

Despite its notoriously mild phenotype, the dystrophin-deficient mdx mouse is the most common model of Duchenne muscular dystrophy (DMD). By mimicking a human DMD-associated metabolic comorbidity, hyperlipidemia, in mdx mice by inactivating the apolipoprotein E gene (mdx-ApoE) we previously reported severe myofiber damage exacerbation via histology with large fibro-fatty infiltrates and phenotype humanization with ambulation dysfunction when fed a cholesterol- and triglyceride-rich Western diet (mdx-ApoEW). Herein, we performed comparative lipidomic and metabolomic analyses of muscle, liver and serum samples from mdx and mdx-ApoEW mice using solution and high-resolution-magic angle spinning (HR-MAS) 1H-NMR spectroscopy. Compared to mdx and regular chow-fed mdx-ApoE mice, we observed an order of magnitude increase in lipid deposition in gastrocnemius muscle of mdx-ApoEW mice including 11-fold elevations in -CH3 and -CH2 lipids, along with pronounced elevations in serum cholesterol, fatty acid, triglyceride and phospholipids. Hepatic lipids were also elevated but did not correlate with the extent of muscle lipid infiltration or differences in serum lipids. This study provides the first lipometabolomic signature of severe mdx lesions exacerbated by high circulating lipids and lends credence to claims that the liver, the main regulator of whole-body lipoprotein metabolism, may play only a minor role in this process. [ABSTRACT FROM AUTHOR]

Introduction and Objective. Probiotics, defined as live microorganisms that provide health benefits when consumed in sufficient quantities, have gained attention in the sports community. The surge in popularity of long-distance athletic competitions such as marathons, triathlons, and cycling races has led to heightened rivalry and a rising curiosity in strategies to improve sports performance. Studies have suggested that probiotics could be a valuable aid for athletes looking to improve their well-being and overall progress. Methods. A literature review was conducted using PubMed and Google Scholar with search terms like "probiotics", "gut microflora", "probiotics in sport", "human microbiome", "athletic performance", "human microbiome", "diet supplementation" and related variations. Articles published within the last five years were prioritized. Brief description of the state of Knowledge. Probiotic supplementation has been shown to positively impact the health and performance of athletes, primarily through modulation of the microbiota-gut-brain axis. This review examines the influence of probiotic supplements on athletic performance, focusing on their effects on gut microbiota, immune support, mental health, anti-inflammatory properties, and overall performance enhancement. Conclusions. Probiotics have been found to have numerous health benefits within the microbiota-gut-brain axis, making them an emerging area of research in athletes. The aim of this research is to understand the potential impacts on athletes experiencing health issues such as gastrointestinal symptoms, lowered immune system, mental disorders, excessive inflammation, or those looking to improve endurance and performance. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) and physical exercise (EX) are well‐established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long‐term follow‐up. This study compared BioAge biomarkers in 41 middle‐aged and older adult long‐term CR practitioners, 41 age‐ and sex‐matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood‐biomarkers. Additionally, a subset of participants (12 CR, 11 EX, and 12 WD) underwent multi‐omic profiling, including DNA methylation and RNAseq of colon mucosa, blood metabolomics, and stool metagenomics. A group of six young WD subjects (yWD) served as a reference for BioAge calculation using Mahalanobis distance across six omic layers. The results demonstrated consistently lower BioAge biomarkers in both CR and EX groups compared to WD controls across all layers. CR participants exhibited lower BioAge in gut microbiome and blood‐derived omics, while EX participants had lower BioAge in colon mucosa‐derived epigenetic and transcriptomic markers, suggesting potential tissue‐specific effects. Multi‐omic pathway enrichment analyses suggested both shared and intervention‐specific mechanisms, including oxidative stress and basal transcription as common pathways, with ether lipid metabolism uniquely enriched in CR. Despite limitations due to sample size, these findings contribute to the broader understanding of the potential anti‐aging effects of CR and EX, offering promising directions for further research. [ABSTRACT FROM AUTHOR]

Background: Thymidine phosphorylase (TYMP) promotes platelet activation and thrombosis while suppressing vascular smooth muscle cell (VSMC) proliferation. Both processes are central to the development and progression of abdominal aortic aneurysms (AAAs). We hypothesize that TYMP plays a role in AAA development. Methods: Male wild‐type (WT) C57BL/6J and Tymp−/− mice, fed a Western diet (WD) (TD.88137), were subjected to the 4‐week Ang II infusion–induced AAA model. AAA progression was monitored by echography and confirmed through necropsy. Whole‐body inflammation was assessed using a plasma cytokine array. Mechanistic studies were conducted using TYMP‐overexpressing rat VSMC cell lines and primary VSMCs cultured from WT and Tymp−/− mouse thoracic aortas. Histological studies were performed on human AAA and normal aorta samples. Results: Elevated TYMP levels were observed in human AAA vessel walls. While WT mice exhibited a 28.6% prevalence of Ang II infusion–induced AAA formation, Tymp−/− mice were protected. TYMP enhanced MMP2 expression, secretion, and activation in VSMCs, which was inhibited by tipiracil, a selective TYMP inhibitor. Systemically, TYMP promoted proinflammatory cytokine expression, and its absence attenuated TNF‐α‐induced MMP2 and AKT activation. WT VSMCs treated with platelets lacking TYMP showed a higher proliferation rate than cells treated with WT platelets. Additionally, TYMP increased activated TGFβ1 expression in cultured VSMCs and human AAA vessel walls. In WT VSMCs, TYMP augmented thrombospondin‐1 type 1 repeat domain (TSR)–stimulated TGFβ1 signaling, increasing connective tissue growth factor and MMP2 production. TSR also enhanced AKT activation in WT VSMCs but had the opposite effect in Tymp−/− cells. TSR‐enhanced MMP2 activation in WT VSMCs was attenuated by LY294002 (a PI3K inhibitor) but not by SB431542 (a TGFβ1 inhibitor); both inhibitors had indiscernible effects on Tymp−/− VSMC. Conclusion: TYMP emerges as a novel regulatory force in vascular biology, influencing VSMC function and inflammatory responses to promote AAA development. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and accompanying dementia, including Alzheimer's Disease (AD), yet the mechanisms underlying this comorbidity remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the APOE-ε4 risk variant among the population and an absence of a similar predisposition among relatives residing in Mexico – suggesting a role for environmental factors in coincident T2D and AD susceptibility. We therefore sought to test if differences in gut community structure could be observed in this population prior to any AD diagnosis. Here, in a small clinical trial (ClinicalTrials.gov Identifier NCT04602650), we report evidence for altered gut microbial ecology among subjects of Mexican descent living in South Texas with T2D (sT2D) compared to healthy controls without T2D (HC), despite no differences in expressed dietary preferences. We performed metataxonomic 16S rRNA gene amplicon sequencing of study participant stool samples. Although no significant decrease in microbial alpha diversity was observed between sT2D gut communities versus those of HC, body mass index was identified as a driver of gut community structure. Intriguingly, we observed a significant negative association of Faecalibacterium and Lachnospiraceae with T2D and an increase in the abundance of pathobionts Escherichia-Shigella , Enterobacter , and the erysipelotrichial species Clostridia innocuum among sT2D gut microbiota, as well as differentially abundant gene and metabolic pathways. Future large-scale, longitudinal sequencing efforts of the gut microbiome of individuals with T2D who go on to develop AD might identify key actors among "disease state" microbiota that contribute to increased susceptibility to comorbid dementia. Finally, we identified candidate microbiome-targeted approaches for the treatment of T2D. [ABSTRACT FROM AUTHOR]

ABSTRACT Acrylamide (AA) and 5‐hydroxymethylfurfural (HMF) are the byproducts of the Maillard reaction that pose health risks due to their high exposure to the Western diet. Current study examines the impact of yeast fermentation on AA, HMF formation, and chemical composition of French fries. Fermentation, known for enriching food with beneficial probiotics, vitamins, and minerals, is coupled with blanching, a technique used to inactivate enzymes and reduce microbial load, thus preserving color and extending shelf life. Fermentation reduced HMF and AA levels in French fries by approximately 86.5% and 54.78%, respectively. Furthermore, combining fermentation with blanching treatment further decreased HMF and AA levels by 88.62% and 59.81%, respectively. This research suggests that yeast fermentation, particularly when combined with blanching treatment, can effectively mitigate the formation of AA and HMF in French fries, thereby potentially reducing their health risks. This pioneering research opens avenues for additional inquiries, laying the groundwork for future advancements in enhancing food safety. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction‐associated steatotic liver disease (MASLD) refers to a broad spectrum of conditions associating fat accumulation in the liver (steatosis) with varying degrees of inflammation (hepatitis) and fibrosis, which can progress to cirrhosis and potentially cancer (hepatocellular carcinoma). The first stages of these diseases are reversible and the immune system, together with metabolic factors (obesity, insulin resistance, Western diet, etc.), can influence the disease trajectory leading to progression or regression. Dendritic cells are professional antigen‐presenting cells that constantly sense environmental stimuli and orchestrate immune responses. Herein, we discuss the existing literature on the heterogeneity of dendritic cell lineages, states, and functions, to provide a comprehensive overview of how liver dendritic cells influence the onset and evolution of MASLD. [ABSTRACT FROM AUTHOR]

Ancient Native American ancestors (Clovis) have been interpreted as either specialized megafauna hunters or generalist foragers. Supporting data are typically indirect (toolkits, associated fauna) or speculative (models, actualistic experiments). Here, we present stable isotope analyses of the only known Clovis individual, the 18-month-old Anzick child, to directly infer maternal protein diet. Using comparative fauna from this region and period, we find that mammoth was the largest contributor to Clovis diet, followed by elk and bison/camel, while the contribution of small mammals was negligible, broadly consistent with the Clovis zooarchaeological record. When compared with second-order consumers, the Anzick-1 maternal diet is closest to that of scimitar cat, a mammoth specialist. Our findings are consistent with the Clovis megafaunal specialist model, using sophisticated technology and high residential mobility to subsist on the highest ranked prey, an adaptation allowing them to rapidly expand across the Americas south of the Pleistocene ice sheets. [ABSTRACT FROM AUTHOR]

Background: polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte telomere length (LTL) is unknown. Additionally, the impact of circulating PUFA on LTL remains controversial in observational studies. Methods: Using publicly accessible datasets, a genome-wide association study (GWAS) was carried out to determine genetic association estimates for BMI, circulating PUFAs, and LTL. The circulating PUFAs considered were omega-3 PUFAs (i.e., docosahexaenoic acid (DHA) and total omega-3 PUFAs) and omega-6 PUFAs (i.e., linoleic acid (LA) and total omega-6 PUFAs). Two-sample Mendelian randomization (MR) was used to investigate the causal relationships between BMI and PUFA with LTL. Additionally, we examined whether certain PUFA mediate the impact of BMI on LTL. Results: None of the evidence supported a causal effect of genetically predicted DHA and total omega-3 PUFA on LTL (DHA: β = 0.001, 95% CI: −0.023 to 0.026, p = 0.926; total omega-3 PUFA: β = 0.008, 95% CI: −0.013 to 0.029, p = 0.466). After conducting sensitivity analyses to account for various models of horizontal pleiotropy, the causal association between higher levels of LA and longer LTL persisted (β = 0.034, 95% CI 0.016 to 0.052, p < 0.001). Adjusting for LA in genetics reduced the effect of BMI on LTL from β = -0.039 (95% CI: -0.058 to -0.020, p < 0.001) to -0.034 (95% CI: -0.054 to -0.014, p < 0.001). Conclusions: This MR study indicates that an increase in genetically predicted circulating LA levels is associated with longer LTL. Additionally, it appears that circulating LA levels play a role in mediating some of the impact that BMI has on LTL. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all HF cases, yet evidence-based therapies remain lacking due to limited understanding of its underlying pathological mechanisms. Our study aimed to uncover early pathological mechanisms in HFpEF by exposing mice to dietary conditions resembling a Western diet—rich in fats, salt, and low in fiber—alongside excess mineralocorticoids to replicate significant aspects of human HFpEF. Echocardiography was performed at both 3-wk and 6-wk intervals postchallenge, revealing cardiac alterations as early as 3 wk. While ejection fraction remained preserved, mice exhibited signs of diastolic dysfunction, reduced stroke volume, and left atrial enlargement. In addition, changes in pulmonary flow velocities were noted by the 3-wk mark, suggesting elevated pulmonary pressure. Extracardiac comorbidities included organ congestion, increased adiposity, impaired glucose tolerance, and hypercholesterolemia. Molecular analyses unveiled evidence of low-grade inflammation, oxidative stress, and impaired NO-cGMP-PKG signaling, contributing to the observed decrease in titin phosphorylation, thereby impacting myocardial stiffness. In addition, impaired nitric oxide (NO) signaling might have influenced the alterations observed in coronary flow reserve. Moreover, dysregulation of calcium signaling in cardiomyocytes and reduced sarcoplasmic reticulum (SR) load were observed. Interestingly, elevated phosphorylation of cMyBP-C was linked to preserved ejection fraction despite reduced SR load. We also observed intestinal atrophy, possibly due to a high-fat diet, low dietary fiber intake, and diminished gut perfusion, potentially contributing to systemic low-grade inflammation. These findings reveal how excess mineralocorticoid salt-induced hypertension and dietary factors, like high-fat and low-fiber intake, contribute to cardiac dysfunction and metabolic disturbances, offering insights into early HFpEF pathology in this model. NEW & NOTEWORTHY: Our study demonstrates that feeding mice a Western diet rich in fat and salt and low in fiber alongside excess mineralocorticoids replicates aspects of human HFpEF. Cardiac alterations including diastolic dysfunction and decreased stroke volume with preserved ejection fraction were observed. Extracardiac effects included organ congestion, adiposity, glucose intolerance, and intestinal atrophy. Molecular analysis revealed inflammation, oxidative stress, impaired NO-cGMP-PKG signaling pathways, and altered calcium signaling in cardiomyocytes, shedding light on early pathological changes in HFpEF. [ABSTRACT FROM AUTHOR]