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Pharmacological Research Jul 2024Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound...
Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.
PubMed: 38960011
DOI: 10.1016/j.phrs.2024.107289 -
Free Radical Biology & Medicine Jul 2024Abnormal polarization of adipose tissue macrophages (ATMs) results in low-grade systemic inflammation and insulin resistance (IR), potentially contributing to the...
Excessive palmitic acid disturbs macrophage α-ketoglutarate/succinate metabolism and causes adipose tissue insulin resistance associated with Gestational Diabetes Mellitus.
Abnormal polarization of adipose tissue macrophages (ATMs) results in low-grade systemic inflammation and insulin resistance (IR), potentially contributing to the development of diabetes. However, the underlying mechanisms that regulate the polarization of ATMs associated with gestational diabetes mellitus (GDM) remain unclear. Thus, we aimed to determine the effects of abnormal fatty acids on macrophage polarization and development of insulin resistance in GDM. Levels of fatty acids and inflammation were assessed in the serum samples and adipose tissues of patients with GDM. An in vitro cell model treated with palmitic acid was established, and the mechanisms of palmitic acid in regulating macrophage polarization was clarified. The effects of excessive palmitic acid on the regulation of histone methylations and IR were also explored in the high-fat diet induced GDM mice model. We found that pregnancies with GDM were associated with increased levels of serum fatty acids, and inflammation and IR in adipose tissues. Increased palmitic acid could induce mitochondrial dysfunction and excessive ROS levels in macrophages, leading to abnormal cytoplasmic and nuclear metabolism of succinate and α-ketoglutarate (αKG). Specifically, a decreased nuclear αKG/succinate ratio could attenuate the enrichment of H3K27me3 at the promoters of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, leading to cytokine secretion. Importantly, GDM mice treated with GSK-J4, an inhibitor of histone lysine demethylase, were protected from abnormal pro-inflammatory macrophage polarization and excessive production of pro-inflammatory cytokines. Our findings highlight the importance of the metabolism of αKG and succinate as transcriptional modulators in regulating the polarization of ATMs and the insulin sensitivity of adipose tissue, ensuring a normal pregnancy. This novel insight sheds new light on gestational fatty acid metabolism and epigenetic alterations associated with GDM.
PubMed: 38960008
DOI: 10.1016/j.freeradbiomed.2024.06.029 -
Veterinary Journal (London, England :... Jul 2024Many studies have shown a strong correlation between Hindgut Acidosis (HGA) and the occurrence of laminitis in horses; therefore, the early diagnosis of HGA is...
Many studies have shown a strong correlation between Hindgut Acidosis (HGA) and the occurrence of laminitis in horses; therefore, the early diagnosis of HGA is essential. In this study, we investigated changes in the plasma concentrations of lipopolysaccharide-binding protein (LBP) and serum amyloid A (SAA) as inflammatory markers in horses with laminitis. Sixteen healthy male Arabian horses that had cecal cannulation without visible laminitis or general symptoms were randomly divided into two groups. The horses were fed two different diets in a forage-to-concentrate ratio. Blood samples were collected on Days 1, 10, and 20. The primary objective of this study was to analyze plasma levels of LBP and SAA. Cecal specimens were obtained from each equine subject on three designated days: days 1, 10, and 20. The second objective was to assess the levels of pH and volatile fatty acids (VFA) in the samples. Throughout the study period, horses fed a high-concentrate diet exhibited a significantly elevated average lameness grade on days 10 and 20 compared to the initial stage (P < 0.001). On day 20, a significant increase in the concentration of SAA was observed in horses fed a high-concentrate diet, in contrast to the initial stage of the study. LBP levels in the plasma were significantly elevated on days 10 and 20 in horses fed a high-concentrate diet. Based on our findings, it is recommended that the evaluation of plasma LBP concentrations is more effective than SAA for the early identification of HGA in horses fed a high-grain diet.
PubMed: 38959999
DOI: 10.1016/j.tvjl.2024.106190 -
Immunology Letters Jul 2024Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an...
BACKGROUND
Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated.
METHODS
An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis.
RESULTS
Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function.
CONCLUSION
Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.
PubMed: 38959983
DOI: 10.1016/j.imlet.2024.106890 -
Cell Host & Microbe Jun 2024The gut microbiota and diet-induced changes in microbiome composition have been linked to various liver diseases, although the specific microbes and mechanisms remain...
The gut microbiota and diet-induced changes in microbiome composition have been linked to various liver diseases, although the specific microbes and mechanisms remain understudied. Alcohol-related liver disease (ALD) is one such disease with limited therapeutic options due to its complex pathogenesis. We demonstrate that a diet rich in soluble dietary fiber increases the abundance of Bacteroides acidifaciens (B. acidifaciens) and alleviates alcohol-induced liver injury in mice. B. acidifaciens treatment alone ameliorates liver injury through a bile salt hydrolase that generates unconjugated bile acids to activate intestinal farnesoid X receptor (FXR) and its downstream target, fibroblast growth factor-15 (FGF15). FGF15 promotes hepatocyte expression of ornithine aminotransferase (OAT), which facilitates the metabolism of accumulated ornithine in the liver into glutamate, thereby providing sufficient glutamate for ammonia detoxification via the glutamine synthesis pathway. Collectively, these findings uncover a potential therapeutic strategy for ALD involving dietary fiber supplementation and B. acidifaciens.
PubMed: 38959900
DOI: 10.1016/j.chom.2024.06.008 -
Cell Reports. Medicine Jun 2024Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear...
Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology.
PubMed: 38959887
DOI: 10.1016/j.xcrm.2024.101639 -
Cell Reports. Medicine Jul 2024Weight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of...
Weight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of weight-loss maintenance. Here, we profile energy-balance-regulating metabokines and sphingolipids in adults with obesity undergoing an initial low-calorie diet-induced weight loss and a subsequent weight-loss maintenance phase with exercise, glucagon-like peptide-1 (GLP-1) analog therapy, both combined, or placebo. We show that circulating growth differentiation factor 15 (GDF15) and C16:0-C18:0 ceramides transiently increase upon initial diet-induced weight loss. Conversely, circulating fibroblast growth factor 21 (FGF21) is downregulated following weight-loss maintenance with combined exercise and GLP-1 analog therapy, coinciding with increased adiponectin, decreased leptin, and overall decrements in ceramide and sphingosine-1-phosphate levels. Subgroup analyses reveal differential alterations in FGF21-adiponectin-leptin-sphingolipids between weight maintainers and regainers. Clinically, cardiometabolic health outcomes associate with selective metabokine-sphingolipid remodeling signatures. Collectively, our findings indicate distinct FGF21, GDF15, and ceramide responses to diverse phases of weight change and suggest that weight-loss maintenance involves alterations within the metabokine-sphingolipid axis.
PubMed: 38959886
DOI: 10.1016/j.xcrm.2024.101629 -
Cell Metabolism Jul 2024The extent to which modifiable lifestyle factors offset the determined genetic risk of obesity and obesity-related morbidities remains unknown. We explored how the...
The extent to which modifiable lifestyle factors offset the determined genetic risk of obesity and obesity-related morbidities remains unknown. We explored how the interaction between genetic and lifestyle factors influences the risk of obesity and obesity-related morbidities. The polygenic score for body mass index was calculated to quantify inherited susceptibility to obesity in 338,645 UK Biobank European participants, and a composite lifestyle score was derived from five obesogenic factors (physical activity, diet, sedentary behavior, alcohol consumption, and sleep duration). We observed significant interaction between high genetic risk and poor lifestyles (p < 0.001). Absolute differences in obesity risk between those who adhere to healthy lifestyles and those who do not had gradually expanded with an increase in polygenic score. Despite a high genetic risk for obesity, individuals can prevent obesity-related morbidities by adhering to a healthy lifestyle and maintaining a normal body weight. Healthy lifestyles should be promoted irrespective of genetic background.
Topics: Humans; Obesity; Male; Female; Life Style; Middle Aged; Genetic Predisposition to Disease; Body Mass Index; Risk Factors; Adult; Aged; Exercise; Sedentary Behavior; United Kingdom
PubMed: 38959863
DOI: 10.1016/j.cmet.2024.06.004 -
Current Opinion in Psychology Jun 2024Machine Learning (ML) affords researchers tools to advance beyond research methods commonly employed in psychology, business, and public policy studies of federal... (Review)
Review
Machine Learning (ML) affords researchers tools to advance beyond research methods commonly employed in psychology, business, and public policy studies of federal nutrition programs and participant food decision-making. It is a sub domain of AI that is applied for feature extraction - a crucial step in decision making. These features are used in context-specific automated decisions resulting in predictive AI models. Whereas many prior studies rely on retrospective, static, "one-shot" decision-making in controlled laboratory environments, ML allows researchers to refine predictions about participation and food behaviors using large-scale datasets. We propose a case study using ML to predict an aspect of participation in a large, publicly funded nutrition education program (The Expanded Food and Nutrition Education Program). Participation has important downstream implications for diet quality, food security, and other important nutrition related decisions. We then suggest a process for validating the ML insights using qualitative research and survey data.
PubMed: 38959778
DOI: 10.1016/j.copsyc.2024.101830 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024Cardiovascular diseases are the leading cause of mortality worldwide, originating in the first decades of life. A better understanding of their early determinants would...
BACKGROUND & AIMS
Cardiovascular diseases are the leading cause of mortality worldwide, originating in the first decades of life. A better understanding of their early determinants would allow for better prevention. This study aimed to evaluate the impact of nutritional and activity-related characteristics during adolescence on young adult cardiovascular risk factors.
METHODS
The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study included adolescents (aged 12.5-17.5 years) in 10 European centres. Four centres designed a nested cohort including 236 participants who were reassessed as young adults (21-32 years). Food consumption was evaluated by dietary recalls, physical activity by accelerometers, physical fitness using physical tests and nutritional knowledge by questionnaires. Cardiovascular health was assessed by Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study risk scores and its components. Factors associated with cardiovascular risk were identified using a multivariable regression model.
RESULTS
Higher Diet Quality Index (DQI, P = 0.012) and nutritional knowledge (P = 0.015) were significantly associated with lower modified PDAY risk scores. Ultra-processed foods were associated with a lower non-high-density lipoprotein (non-HDL) cholesterol (P = 0.003), whereas DQI (P = 0.014) and Planetary Health Diet Index (P = 0.016) were associated with a higher HDL cholesterol. Higher DQI was also related to a lower body mass index (BMI, P = 0.006). In addition, cardiorespiratory fitness was related to a lower BMI (P = 0.004).
CONCLUSIONS
Nutritional knowledge, diet quality and adherence to a sustainable diet in adolescence decrease cardiovascular risk in adulthood, whereas ultra-processed food consumption increases risk. These factors appear as targeted prevention tools for promoting a healthier adolescent lifestyle to decrease long-term cardiovascular risk.
CLINICAL TRIAL REGISTRY NUMBER
Clinicaltrials.gov NCT02899416.
PubMed: 38959665
DOI: 10.1016/j.clnu.2024.06.022