Obesity is associated with systemic inflammation that impairs mitochondrial function. This disruption curtails oxidative metabolism, limiting adipocyte lipid metabolism and thermogenesis, a metabolically beneficial program that dissipates chemical energy as heat. Here, we show that PGC1α, a key governor of mitochondrial biogenesis, is negatively regulated at the level of its mRNA translation by the RNA-binding protein RBM43. RBM43 is induced by inflammatory cytokines and suppresses mitochondrial biogenesis in a PGC1α-dependent manner. In mice, adipocyte-selective Rbm43 disruption elevates PGC1α translation and oxidative metabolism. In obesity, Rbm43 loss improves glucose tolerance, reduces adipose inflammation, and suppresses activation of the innate immune sensor cGAS-STING in adipocytes. We further identify a role for PGC1α in safeguarding against cytoplasmic accumulation of mitochondrial DNA, a cGAS ligand. The action of RBM43 defines a translational regulatory axis by which inflammatory signals dictate cellular energy metabolism and contribute to metabolic disease pathogenesis.

Insulin resistance is major factor in the development of metabolic syndrome and type 2 diabetes (T2D). We extracted 430 genes from literature associated with both insulin resistance and inflammation. The highly significant pathways were Toll-like receptor signaling, PI3K-Akt signaling, cytokine-cytokine receptor interaction, pathways in cancer, TNF signaling, and NF-kappa B signaling. Among the 297 common genes in all datasets of various T2D patients' tissues including blood, muscle, liver, pancreas, and adipose tissues, 71% and 60% of these genes were differentially expressed in pancreas (GSE25724) and liver (GSE15653), respectively. A total of 169 genes contain highly conserved motifs for various transcription factors involved in immune response, thereby suggesting coordinated expression. Through co-expression analysis, we obtained three modules. The respective modules had 78, 158, and 55 genes, and TRAF2, HMGA1, and RGS5 as hub genes. Further, we used the BioNSi pathways simulation tool and identified the following five KEGG pathways perturbed in four or more tissues, namely Toll-like receptor signaling pathway, RIG-1-like receptor signaling pathway, pathways in cancer, NF-kappa B signaling pathway, and insulin resistance pathway. The genes NFKBIA and IKBKB are common to all these five pathways. In addition, using the NF-κB computational activation model, we identified that the reversal of NF-κB constitutive activation through overexpression of NFKB1 (P50 homodimer), PPARG, PIAS3 could reduce insulin resistance by almost half of its original value. To conclude, co-expression studies, gene expression network simulation, and NF-κB computational modeling substantiate the causal role of NF-κB pathway in insulin resistance. These results taken together with other published evidence suggests that the TNF-TRAF2-IKBKB-NF-κB axis could be explored as a potential target in combination with available metabolic targets in the management of insulin resistance.

The online version contains supplementary material available at 10.1007/s13205-024-04202-4.

Although lipid-derived acetyl-coenzyme A (CoA) is a major carbon source for histone acetylation, the contribution of fatty acid β-oxidation (FAO) to this process remains poorly characterized. To investigate this, we generated mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1, distal FAO enzyme) knockout macrophages. 13C-carbon tracing confirmed reduced FA-derived carbon incorporation into histone H3, and RNA sequencing identified diminished interferon-stimulated gene expression in the absence of ACAT1. Chromatin accessibility at the Stat1 locus was diminished in ACAT1-/- cells. Chromatin immunoprecipitation analysis demonstrated reduced acetyl-H3 binding to Stat1 promoter/enhancer regions, and increasing histone acetylation rescued Stat1 expression. Interferon-β release was blunted in ACAT1-/- and recovered by ACAT1 reconstitution. Furthermore, ACAT1-dependent histone acetylation required an intact acetylcarnitine shuttle. Last, obese subjects' monocytes exhibited increased ACAT1 and histone acetylation levels. Thus, our study identifies an intriguing link between FAO-mediated epigenetic control of type I interferon signaling and uncovers a potential mechanistic nexus between obesity and type I interferon signaling.

A slew of common metabolic disorders, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease and steatohepatitis, are exponentially increasing in our sedentary and overfed society. While macronutrients directly impact metabolism and bioenergetics, new evidence implicates immune cells as critical sensors of nutritional cues and important regulators of metabolic homeostasis. A deeper interrogation of the intricate and multipartite interactions between dietary components, immune cells and metabolically active tissues is needed for a better understanding of metabolic regulation and development of new treatments for common metabolic diseases. Responding to macronutrients and micronutrients, immune cells play pivotal roles in interorgan communication between the microbiota, small intestine, metabolically active cells including hepatocytes and adipocytes, and the brain, which controls feeding behavior and energy expenditure. This Review focuses on the response of myeloid cells and innate lymphocytes to dietary cues, their cross-regulatory interactions and roles in normal and aberrant metabolic control.

Manganese (Mn), a trace element, has been documented to exert an important role in the metabolism of cholesterol. Cholesterol gallstone (CG) pathogenesis is directly linked to biliary cholesterol imbalance which could be due to diabetes complications or mismanagement. NF-κβ pathway, an inflammatory regulator, has been implicated in metabolic disease especially in the context of diabetes and gallstone formation. However, the management of cholesterol gallstones due to diabetes with trace elements is vague. This study investigates the probable role of manganese during CG formation due to diabetes complications. Eighty female Swiss mice were grouped: I (control), II (untreated CG), III and IV (normal mice treated 0.37 mg/kg and 0.74 mg/kg Mn, respectively), V and VI (CG treated 0.37 mg/kg and 0.74 mg/kg Mn, respectively), and VII and VIII (CG treated 75 mg/7 kg and 350 mg/kg aspirin, respectively). Experimental CG was induced with cholesterol-rich diets after alloxan-induced diabetes. On sacrifice, blood collected was evaluated for complete hematological analysis and biochemistry while the excised liver was assayed for biochemical variables. Results were subjected to one-way ANOVA values were expressed as Mean ± SEM and significant at p ≤ 0.05. Manganese treatment significantly increased packed cell volume, RBC count, and hemoglobin with decreased platelet and leukocyte counts, liver enzymes (AST, ALT, and ALP), BUN, and creatinine levels in CG groups compared with untreated CG. Blood glucose, plasma low-density lipoproteins, and liver malodialdehyde levels were significantly reduced while liver nitric-oxide, sulfhydryl, and glutathione levels increased significantly in manganese-treated groups compared with untreated CG. Manganese significantly increased fecal iron contents in normal mice by the 2nd week. Hepatocytes and gallbladder histology appear normal in manganese-treated groups. Liver NF-Kβ immunoreactivity was downregulated in manganese-treated CG groups. Manganese attenuated experimental hyperglycemia-induced cholesterol gallstone by ameliorating liver oxidative stress and NF-Kβ inflammatory pathway.

Metabolically unhealthy non-obese (MUNO) individuals are at higher risk of cardiovascular diseases, while not receiving sufficient attention. This study was conducted to explore the association between BMI-adjusted CC and MUNO in non-obese US adults using the NHANES database.

A total of 9,628 non-obese US adults (48.01% female and 51.99% male) were included in this cross-sectional study. The metabolically unhealthy phenotype was defined as ≥ 2 components of metabolic abnormalities. BMI-adjusted CC and BMI-adjusted skeletal muscle mass (SMM) were divided into quartiles. Weighted multiple logistic regression model was used to evaluate the study aims. The relation between BMI-adjusted CC and BMI-adjusted SMM was tested by Spearman correlation.

In the multivariate analysis, compared with the lowest quartile of BMI-adjusted CC and BMI-adjusted SMM, OR (95%CI) of the highest quartile was 0.30 (0.25, 0.35) (P < 0.001, P for trend < 0.001) and 0.39 (0.29, 0.53) (P < 0.001, P for trend < 0.001), respectively. BMI-adjusted CC was positively correlated with BMI-adjusted SMM for all participants (r = 0.48). A weak non-linear association was observed in BMI-adjusted CC and MUNO (P = 0.047). Similar results were observed in sex- and BMI-specific subgroup and sensitivity analysis.

BMI-adjusted CC was inversely associated with MUNO, suggesting more attention should be paid to monitoring BMI-adjusted CC for the public to ease the disease burden, especially for people without obesity.

Nonalcoholic fatty liver disease (NAFLD) is characterized by over 5% hepatic fat accumulation without secondary causes. The prevalence of NAFLD has escalated in recent years due to shifts in dietary patterns and socioeconomic status, making it the most prevalent chronic liver disease and a significant public health concern globally. Serum uric acid (SUA) serves as the end product of purine metabolism in the body and is intricately linked to metabolic syndrome. Elevated SUA levels have been identified as an independent risk factor for the incidence and progression of NAFLD. This paper reviews the relationship between SUA and NAFLD, the underlying mechanisms of SUA involved in NAFLD, and the potential benefits of SUA-lowering therapy in treating NAFLD. The aim is to raise awareness of SUA management in patients with NAFLD, and to encourage further investigation into pharmacological interventions in this area.

In this study, we selected Sitona callosus, one of the primary insect pests of alfalfa, as the experimental insect and infected it with Beauveria bassiana. Transcriptomic and metabolomic analyses were conducted to explore alterations in gene expression and metabolic processes in S. callosus at 48, 96, and 144 h post infection with B. bassiana. The transcriptomic analysis unveiled that B. bassiana infection boosted immune responses in tubercula, affecting carbohydrate metabolism, cytochrome P450 activity, lysosome function, apoptosis regulation, phagosome formation, glutathione metabolism, amino acid metabolism, and pathogen response pathways. Subsequent metabolomics analysis confirmed that glycerophospholipids, carboxylic acids and derivatives, organooxygen compounds, keto acids and derivatives, and azane immune metabolites were significantly upregulated in response to B. bassiana infection. Additionally, we utilized the Pearson correlation coefficient method to examine the relationships between differentially expressed immune-related genes and metabolites, revealing notably strong correlations between these two sets of variables. By leveraging the WGCNA method to analyze immune metabolite data for immune-related genes, we identified hub genes crucial at various stages of immune activation. These central genes predominantly included C-type lectin receptors for pattern recognition, cytochrome P450 enzymes linked to detoxification processes, and cathepsin proteases. By combining transcriptome and metabolome analyses, it was determined that autophagy and arachidonic acid metabolism play significant roles in the response of S. callosus to infection by B. bassiana. This research will facilitate the understanding of the immune response to B. bassiana infection in adult S. callosus, laying a theoretical groundwork for future biological control strategies targeting S. callosus.

Nutrient-sensing pathways undergo deregulation in aged animals, exerting a pivotal role in regulating the cell cycle and subsequent stem cell division. Nevertheless, their precise functions in governing pluripotent stem cell differentiation remain largely elusive. Here, we uncovered a significant alteration in the cellular constituents of the intestinal epithelium in aged humans and mice. Employing Drosophila midgut and mouse organoid culture models, we made an observation regarding the altered trajectory of differentiation in intestinal stem cells (ISC) during overnutrition or aging, which stems from the erroneous activation of the insulin receptor signaling pathway. Through genetic analyses, we ascertained that the nutrient-sensing pathway regulated the direction of ISC differentiation by modulating the maturation of endosomes and SOX21A transcription factor. This study elucidates a nutrient-sensing pathway-mediated mechanism underlying stem cell differentiation, offering insights into the etiology of stem cell dysfunction in aged animals, including humans.

The COVID-19 pandemic has caused a global health crisis and significant social economic burden. While most individuals experience mild or non-specific symptoms, elderly individuals are at a higher risk of developing severe symptoms and life-threatening complications. Exploring the key factors associated with clinical severity highlights that key characteristics of aging, such as cellular senescence, immune dysregulation, metabolic alterations, and impaired regenerative potential, contribute to disruption of tissue homeostasis of the lung and worse clinical outcome. Senolytic and senomorphic drugs, which are anti-aging treatments designed to eliminate senescent cells or decrease the associated phenotypes, have shown promise in alleviating age-related dysfunctions and offer a novel approach to treating diseases that share certain aspects of underlying mechanisms with aging, including COVID-19. This review summarizes the current understanding of aging in COVID-19 progression, and highlights recent findings on anti-aging drugs that could be repurposed for COVID-19 treatment to complement existing therapies.

1. The poultry microbiome and its stability at every point in time, either free range or reared under different farming systems, is affected by several environmental and innate factors. The interaction of the poultry birds with their microbiome, as well as several inherent and extraneous factors contribute to the microbiome dynamics. A poor understanding of this could worsen poultry heath and result in disease/metabolic disorders.2. Many diseased states associated with poultry have been linked to dysbiosis state, where the microbiome experiences some perturbation. Dysbiosis itself is too often downplayed; however, it is considered a disease which could lead to more serious conditions in poultry. The management of interconnected factors by conventional and emerging technologies (sequencing, nanotechnology, robotics, 3D mini-guts) could prove to be indispensable in ensuring poultry health and welfare.3. Findings showed that high-throughput technological advancements enhanced scientific insights into emerging trends surrounding the poultry gut microbiome and ecosystem, the dysbiotic condition, and the dynamic roles of intrinsic and exogenous factors in determining poultry health. Yet, a combination of conventional, -omics based and other techniques further enhance characterisation of key poultry microbiome actors, their mechanisms of action, and roles in maintaining gut homoeostasis and health, in a bid to avert metabolic disorders and infections.4. In conclusion, there is an important interplay of innate, environmental, abiotic and biotic factors impacting on poultry gut microbiome homoeostasis, dysbiosis, and overall health. Associated infections and metabolic disorders can result from the interconnected nature of these factors. Emerging concepts (interkingdom or network signalling and neurotransmitter), and future technologies (mini-gut models, cobots) need to include these interactions to ensure accurate control and outcomes.

Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/-) mice did not show any significant changes in body weight or composition. However, Fadd+/- mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/- mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

High palmitic acid (PA) levels trigger metainflammation, facilitating the onset and progression of chronic metabolic diseases. Recently, exosomes were identified as new inflammation mediators. However, the mechanism by which macrophage exosomes mediate PA-induced inflammation remains unclear.

To explore how PA induces metainflammation through macrophage exosomes.

Exosomes secreted by RAW264.7 mouse macrophages stimulated with PA (ExosPA) or not (Exos) were prepared by ultracentrifugation. The differential miRNAs between ExosPA and Exos were identified by high-throughput sequencing, and their targeted mRNAs and proteins were bioinformatically analyzed and verified by qPCR and western blot. Mouse macrophages and metabolic cells (AML-12 hepatocytes, C2C12 myocytes or 3T3-L1 adipocytes) were treated with ExosPA or Exos. The verified miRNAs and its targeted molecules related to inflammation were analyzed in recipient cells. Furthers, exosomes were prepared from primary peritoneal macrophages isolated from AIN93G diet-fed (Control PM-Exos) or HPD-fed (PA PM-Exos) mice. Control or PA PM-Exos were then tail vein injected (30 μg) into mice (n = 10), once a week for 2 weeks. The verified miRNA and its targets in blood, blood exosomes, and metabolic tissues were detected. Finally, measured the levels of miRNA, inflammatory factors, and fatty acids in the blood of 20 obese/overweight individuals and 20 healthy individuals.

ExoPA activate NF-κB signaling and enhance inflammatory enzyme/cytokine production in macrophages and metabolic cells. ExoPA enrich miR-3064-5p and target to inhibit IκBα as verified by exosome inhibitors and miR-3064-5p mimics and inhibitors. HPD elevates exosomal miR-3064-5p, macrophage exosomal miR-3064-5p, and inflammatory cytokine levels in mice circulation. PA PM-Exos from HPD-fed mice triggered inflammation in the circulation and metabolic tissues/organs of chow diet-fed mice. Overweight/obese individuals exhibit increased levels of circulating palmitoleic acid, exosomal miR-3064-5p, and high-sensitivity C-reactive proteins.

Macrophage exosomes transferring miR-3064-5p to target IκBα and activate NF-κB signaling in metabolic cells is a mechanism of PA-induced metainflammation.

This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations.

A cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2.

The mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality.

Elevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population.

As people age, degenerative bone and joint diseases (DBJDs) become more prevalent. When middle-aged and elderly people are diagnosed with one or more disorders such as osteoporosis (OP), osteoarthritis (OA), and intervertebral disc degeneration (IVDD), it often signals the onset of prolonged pain and reduced functionality. Chronic inflammation has been identified as the underlying cause of various degenerative diseases, including DBJDs. Recently, excessive activation of pyroptosis, a form of programed cell death (PCD) mediated by inflammasomes, has emerged as a primary driver of harmful chronic inflammation. Consequently, pyroptosis has become a potential target for preventing and treating DBJDs.

This review explored the physiological and pathological roles of the pyroptosis pathway in bone and joint development and its relation to DBJDs. Meanwhile, it elaborated the molecular mechanisms of pyroptosis within individual cell types in the bone marrow and joints, as well as the interplay among different cell types in the context of DBJDs. Furthermore, this review presented the latest compelling evidence supporting the idea of regulating the pyroptosis pathway for DBJDs treatment, and discussed the potential, limitations, and challenges of various therapeutic strategies involving pyroptosis regulation.

In summary, an interesting identity for the unregulated pyroptosis pathway in the context of DBJDs was proposed in this review, which was undertaken as a spoiler of peaceful coexistence between cells in a degenerative environment. Over the extended course of DBJDs, pyroptosis pathway perpetuated its activity through crosstalk among pyroptosis cascades in different cell types, thus exacerbating the inflammatory environment throughout the entire bone marrow and joint degeneration environment. Correspondingly, pyroptosis regulation therapy emerged as a promising option for clinical treatment of DBJDs.

Given the growing global threat and rising prevalence of type 2 diabetes mellitus (T2DM), addressing this metabolic disease is imperative. T2DM is preceded by prediabetes (PD), an intermediate hyperglycaemia that goes unnoticed for years in patients. Several studies have shown that gut microbial diversity and glucose homeostasis in PD or T2DM patients are affected. Therefore, this review aims to synthesize the existing literature to elucidate the association between high-calorie diets, intestinal permeability and their correlation with PD or T2DM. Moreover, it discusses the beneficial effects of different dietary interventions on improving gut health and glucose metabolism. The primary factor contributing to complications seen in PD or T2DM patients is the chronic consumption of high-calorie diets, which alters the gut microbial composition and increases the translocation of toxic substances from the intestinal lumen into the bloodstream. This causes an increase in inflammatory response that further impairs glucose regulation. Several dietary approaches or interventions have been implemented. However, only a few are currently in use and have shown promising results in improving beneficial microbiomes and glucose metabolism. Therefore, additional well-designed studies are still necessary to thoroughly investigate whether improving gut health using other types of dietary interventions can potentially manage or reverse PD, thereby preventing the onset of T2DM.

Craniopharyngiomas are rare tumors of the central nervous system that typically present with symptoms such as headache and visual impairment, and those reflecting endocrine abnormalities, which seriously affect the quality of life of patients. Patients with craniopharyngiomas are at higher cardiometabolic risk, defined as conditions favoring the development of type 2 diabetes and cardiovascular disease. However, the underlying common pathogenic mechanisms of craniopharyngiomas and type 2 diabetes are not clear. Especially due to the difficulty of conducting in vitro or in vivo experiments on craniopharyngioma, we thought the common pathway analysis between craniopharyngioma and type 2 diabetes based on bioinformatics is a powerful and feasible method. In the present study, using public datasets (GSE94349, GSE68015, GSE38642 and GSE41762) obtained from the GEO database, the gene expression associated with adamantinomatous craniopharyngioma, a subtype of craniopharyngioma, and type 2 diabetes were analyzed using a bioinformatic approach. We found 11 hub genes using a protein-protein interaction network analysis. Of these, seven (DKK1, MMP12, KRT14, PLAU, WNT5B, IKBKB, and FGF19) were also identified by least absolute shrinkage and selection operator analysis. Finally, single-gene validation and receptor operating characteristic analysis revealed that four of these genes (MMP12, PLAU, KRT14, and DKK1) may be involved in the common pathogenetic mechanism of adamantinomatous craniopharyngioma and type 2 diabetes. In addition, we have characterized the differences in immune cell infiltration that characterize these two diseases, providing a reference for further research.

Because of their role in regulating and fine-tuning gene expression in the posttranscriptional period, microRNA (miRNA) may represent a mediating factor that connects diet and metabolic regulation. Given the vast number of miRNAs and that modulations in miRNA happen in response to a variety of stimuli, a comprehensive registry of miRNAs impacted by diet and the food items that modulate them, would have utility in the identification of miRNA complements for analysis of diet interventions and in helping to establish linkages between the specific impacts of diet components. A scoping literature search of online databases (PubMed, SCOPUS, EMBASE, and Web of Science) was performed. Only studies in human populations, those that used a diet intervention or meal challenge, and those that measured miRNA profiles in the same subject at multiple time points were included. Of the 6167 studies screened, only 25 met the study criteria and were included in the review. Seven studies examined miRNA following a meal challenge, whereas 18 investigated miRNA following a sustained diet intervention. The results demonstrated that miRNA are modulated following a variety of diet interventions and that intensity of miRNA response is greater in metabolically healthy subjects. Heterogeneity in the intensity and length of the diet intervention, the study populations being observed, and the methodology through which target miRNA are identified contribute to a lack of comparability across studies. The findings of this review highlight the need for more study of miRNA responsiveness to intake and provide recommendations for future research.

Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D.

In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test).

There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers.

13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.

Objective. Blood C-reactive protein (CRP) and the electrical bioimpedance spectroscopy (EBIS) variables phase angle (PhA) and impedance ratio (IR) have been proposed as biomarkers of metainflammation in overweight/obesity. CRP involves taking blood samples, while PhA and IR imply a less-than-2-minute-non-invasive procedure. In this study, values for these variables and percent body fat mass (PBFM) were obtained and compared before and immediately after a colon cleansing protocol (CCP), aimed at modulating intestinal microbiota and reducing metainflammation, as dysbiosis and the latter are intrinsically related, as well as along a period of 8 weeks after it.Approach. 20 female volunteers (20.9-24.9 years old) participated: 12 in an overweight group (OG), and 8 in a lean group (LG). TheOGwas divided in two subgroups (n= 6, each): control (CSG) and experimental (ESG). TheESGunderwent a 6-day CCP at week 2, while 5 volunteers in theCSGunderwent it at week 9.Main results.Pre/post-CCP mean values for the variables in theOGwere: PBFM (34.3/31.3%), CRP (3.7/0.6 mg dl-1), PhA (6.9/7.5°) and IR*10 (0.78/0.77). CalculatedR2correlation factors among these variables are all above 0.89. The favourable changes first seen in theESGwere still present 8 weeks after the CCP.Significance.(a) the CCP drastically lowers meta-inflammation, (b) EBIS can be used to measure metainflammation, before and after treatment, (c) for microbiota modulation, CCP could be a good alternative to more drastic procedures like faecal microbiota transplantation; (d) reestablishing eubiosis by CCP could be an effective coadjutant in the treatment of overweight young adult women.

Currently, there is limited and inconsistent evidence regarding the risk association between daily dietary intake, antioxidants, minerals, and vitamins with Childhood Asthma (CA). Therefore, this study employs Mendelian Randomization (MR) methodology to systematically investigate the causal relationships between daily dietary intake, serum antioxidants, serum minerals, and the circulating levels of serum vitamins with CA.

This study selected factors related to daily dietary intake, including carbohydrates, proteins, fats, and sugars, as well as serum antioxidant levels (lycopene, uric acid, and β-carotene), minerals (calcium, copper, selenium, zinc, iron, phosphorus, and magnesium), and vitamins (vitamin A, vitamin B6, folate, vitamin B12, vitamin C, vitamin D, and vitamin E), using them as Instrumental Variables (IVs). Genetic data related to CA were obtained from the FinnGen and GWAS Catalog databases, with the primary analytical methods being Inverse Variance Weighting (IVW) and sensitivity analysis.

Following MR analysis, it is observed that sugar intake (OR: 0.71, 95% CI: 0.55-0.91, P: 0.01) is inversely correlated with the risk of CA, while the intake of serum circulating magnesium levels (OR: 1.63, 95% CI: 1.06-2.53, P: 0.03), fats (OR: 1.44, 95% CI: 1.06-1.95, P: 0.02), and serum vitamin D levels (OR: 1.14, 95% CI: 1.04-1.25, P: 0.02) are positively associated with an increased risk of CA.

This study identified a causal relationship between the daily dietary intake of sugars and fats, as well as the magnesium and vitamin D levels in serum, and the occurrence of CA. However, further in-depth research is warranted to elucidate the specific mechanisms underlying these associations.

Recently, lifestyle medicine (LSM) application has shown feasibility for musculoskeletal pain patients with co-existing lifestyle-related chronic diseases. This study describes early results of a LSM program for musculoskeletal patients with goals to optimize health prior to orthopedic surgery. Fifty-four patients (age: 61 ± 11 years; 39 [72%] females) completed the program from 3/8/22-12/1/23. Data included patient goals, utilization, goal attainment, and patient outcomes. Most patients (41/54 [76%]) enrolled with established surgical dates. Mean BMI was 43.2 ± 5.3 kg/m2, and 89% had ≥2 lifestyle-related chronic diseases. The majority reported impaired sleep (79%) and zero cumulative minutes of physical activity/week (57%). Mean program duration was 13 ± 8 weeks involving 5 ± 4 visits with members of the interprofessional team. Fifty-two (96%) patients successfully attained pre-program goals, and 49/54 (91%) met their surgical goal. Of the patients enrolled without surgical dates, 11/13 (85%) optimized their health and proceeded to surgery. Forty-two (78%) patients reported decreases in weight and BMI, averaging 11 ± 7 lbs and 1.8 ± 1.3 kg/m2, respectively. Rates of improvement in pain, PROMIS-10 physical and mental health, and PHQ-4 were 52%, 37%, 45%, and 47%, respectively. These data demonstrate the feasibility and effectiveness of a LSM program to address whole-person health optimization and enable orthopedic patients to improve lifestyle behaviors and proceed to orthopedic surgery.

Inositol requiring enzyme 1 (IRE1) is generally thought to control the most conserved pathway in the unfolded protein response (UPR). Two isoforms of IRE1, IRE1α and IRE1β, have been reported in mammals. IRE1α is a ubiquitously expressed protein whose knockout shows marked lethality. In contrast, the expression of IRE1β is exclusively restricted in the epithelial cells of the respiratory and gastrointestinal tracts, and IRE1β-knockout mice are phenotypically normal. As research continues to deepen, IRE1α was showed to be tightly linked to inflammation, lipid metabolism regulation, cell death and so on. Growing evidence also suggests an important role for IRE1α in promoting atherosclerosis (AS) progression and acute cardiovascular events through disrupting lipid metabolism balance, facilitating cells apoptosis, accelerating inflammatory responses and promoting foam cell formation. In addition, IRE1α was recognized as novel potential therapeutic target in AS prevention. This review provides some clues about the relationship between IRE1α and AS, hoping to contribute to further understanding roles of IRE1α in atherogenesis and to be helpful for the design of novel efficacious therapeutics agents targeting IRE1α-related pathways.

(1) Background: Numerous elements of the Mediterranean diet (MD) have antioxidant and anti-inflammatory qualities. (2) Methods: We present a narrative review of the potential benefits of the Mediterranean dietary pattern (MD) in mitigating aging-related inflammation (inflamm-aging) associated with childhood obesity. The mechanisms underlying chronic inflammation in obesity are also discussed. A total of 130 papers were included after screening abstracts and full texts. (3) Results: A complex interplay between obesity, chronic inflammation, and related comorbidities is documented. The MD emerges as a promising dietary pattern for mitigating inflammation. Studies suggest that the MD may contribute to weight control, improved lipid profiles, insulin sensitivity, and endothelial function, thereby reducing the risk of metabolic syndrome in children and adolescents with obesity. (4) Conclusions: While evidence supporting the anti-inflammatory effects of the MD in pediatric obesity is still evolving, the existing literature underscores its potential as a preventive and therapeutic strategy. However, MD adherence remains low among children and adolescents, necessitating targeted interventions to promote healthier dietary habits. Future high-quality intervention studies are necessary to elucidate the specific impact of the MD on inflammation in diverse pediatric populations with obesity and associated comorbidities.

The appropriate transcriptional activity of PPARγ is indispensable for controlling inflammation, tumor and obesity. Therefore, the identification of key switch that couples PPARγ activation with degradation to sustain its activity homeostasis is extremely important. Unexpectedly, we here show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) critically controls PPARγ activity homeostasis via SIRT1 to enhance adipose plasticity via promoting white adipose tissues beiging and brown adipose tissues thermogenesis. Mechanistically, ACSS2 binds directly acetylated PPARγ in the presence of ligand and recruits SIRT1 and PRDM16 to activate UCP1 expression. In turn, SIRT1 triggers ACSS2 translocation from deacetylated PPARγ to P300 and thereafter induces PPARγ polyubiquitination and degradation. Interestingly, D-mannose rapidly activates ACSS2-PPARγ-UCP1 axis to resist high fat diet induced obesity in mice. We thus reveal a novel ACSS2 function in coupling PPARγ activation with degradation via SIRT1 and suggest D-mannose as a novel adipose plasticity regulator via ACSS2 to prevent obesity.

We investigated whole blood and hepatic mRNA expressions of immune genes and rumen microbiome of crossbred beef steers with divergent residual feed intake phenotype to identify relevant biological processes underpinning feed efficiency in beef cattle. Low-RFI beef steers (n = 20; RFI = - 1.83 kg/d) and high-RFI beef steers (n = 20; RFI = + 2.12 kg/d) were identified from a group of 108 growing crossbred beef steers (average BW = 282 ± 30.4 kg) fed a high-forage total mixed ration after a 70-d performance testing period. At the end of the 70-d testing period, liver biopsies and blood samples were collected for total RNA extraction and cDNA synthesis. Rumen fluid samples were also collected for analysis of the rumen microbial community. The mRNA expression of 84 genes related to innate and adaptive immunity was analyzed using pathway-focused PCR-based arrays. Differentially expressed genes were determined using P-value ≤ 0.05 and fold change (FC) ≥ 1.5 (in whole blood) or ≥ 2.0 (in the liver). Gene ontology analysis of the differentially expressed genes revealed that pathways related to pattern recognition receptor activity, positive regulation of phagocytosis, positive regulation of vitamin metabolic process, vascular endothelial growth factor production, positive regulation of epithelial tube formation and T-helper cell differentiation were significantly enriched (FDR < 0.05) in low-RFI steers. In the rumen, the relative abundance of PeH15, Arthrobacter, Moryella, Weissella, and Muribaculaceae was enriched in low-RFI steers, while Methanobrevibacter, Bacteroidales_BS11_gut_group, Bacteroides and Clostridium_sensu_stricto_1 were reduced. In conclusion, our study found that low-RFI beef steers exhibit increased mRNA expression of genes related to immune cell functions in whole blood and liver tissues, specifically those involved in pathogen recognition and phagocytosis regulation. Additionally, these low-RFI steers showed differences in the relative abundance of some microbial taxa which may partially account for their improved feed efficiency compared to high-RFI steers.

NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, and TLR signaling. The physiological and pathological states of NF-κB signaling, as well as its intricate involvement in inflammation, immune regulation, and tumor microenvironment, are also explicated. Additionally, we illustrate how NF-κB signaling is involved in a variety of human diseases, including cancers, inflammatory and autoimmune diseases, cardiovascular diseases, metabolic diseases, neurological diseases, and COVID-19. Further, we discuss the therapeutic approaches targeting NF-κB signaling, including IKK inhibitors, monoclonal antibodies, proteasome inhibitors, nuclear translocation inhibitors, DNA binding inhibitors, TKIs, non-coding RNAs, immunotherapy, and CAR-T. Finally, we provide an outlook for research in the field of NF-κB signaling. We hope to present a stereoscopic, comprehensive NF-κB signaling that will inform future research and clinical practice.

As meta-inflammation is a common feature for obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease and atherosclerosis, we have proposed a new concept, metabolic inflammatory syndrome (MIS), to cluster such diseases. We aimed to characterize MIS and explore its association with coronary heart disease (CHD) among T2D inpatients in China.

A total number of 8344 T2D participants were enrolled. Each component of MIS and metabolic syndrome (MS) was analyzed. Their association with the risk of CHD was assessed using a binary logistic analysis.

Among the T2D inpatients, the detection rate of MIS was much higher than that of MS (93.6 % vs. 53.2 %). Among all the components of MIS and MS, carotid atherosclerosis (71.9 %) was most commonly detected, which increased with aging in subgroups. Surprisingly, the most common combination of MIS was with all 4 components in T2D patients, with a constituent ratio of 30.9 %. According to the odds ratios (ORs), MIS was a better predictor of CHD than MS, especially after adjustment for age, sex, smoking, and alcohol consumption (adjusted OR for MIS: 3.083; for MS: 1.515). The presence of more components of MIS was associated with a higher detection rate of CHD (P < 0.001). Among all the components of MIS and MS, carotid atherosclerosis best predicted the risk of CHD (adjusted OR: 1.787).

MIS is an independent risk factor for CHD, with a bigger OR value than MS. Carotid atherosclerosis, with the highest detection rate, was the best individual predictor of CHD and thus a critical component of MIS. The concept of MIS represents the understanding of metabolic diseases from the perspective of holistic integrative medicine.

Obesity is closely associated with several chronic diseases, and adipose tissue plays a major role in modulating energy metabolism.

This study aimed to determine whether Mate, derived from I. paraguariensis A.St.-Hil., ameliorates lipid metabolism in 3T3-L1 adipocytes and high-fat diet (HFD)-fed obese Sprague-Dawley (SD) rats.

3T3-L1 adipocytes were cultured for 7 days, following which intracellular lipid accumulation and expression levels of lipid metabolism-related factors were examined. Dorsomorphin was used to investigate the potential pathways involved, particularly the adenosine monophosphate-activated protein kinase (AMPK)- dependent pathway. Mate was administered to rat HFD-fed obese SD models for 8 consecutive weeks. The expression of lipid metabolism-related factors in the organs and tissues collected from dissected SD rats was evaluated.

Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes, increased the protein and gene expression levels of AMPK, hormone sensitive lipase (HSL), calmodulin kinase kinase (CaMKK), liver kinase B1 (LKB1), protein kinase A (PKA), CCAAT/enhancer binding protein β (C/EBPβ), insulin receptor b (IRβ), and insulin receptor substrate 1 (IRS1) (Tyr465), and decreased those of sterol regulatory element binding protein 1C (Srebp1c), fatty acid synthase (FAS), peroxisome-activated receptor γ (PPARγ), and IRS1 (Ser1101). Furthermore, an AMPK inhibitor abolished the effects exerted by Mate on intracellular lipid accumulation and HSL and FAS expression levels. Mate treatment suppressed body weight gain and improved serum cholesterol levels in HFD-fed obese SD rats. Treatment with Mate increased the protein and gene expression levels of AMPK, PKA, Erk1/Erk2 (p44/p42), and uncoupling protein 1 and reduced those of mammalian target of rapamycin, S6 kinase, Srebp1c, ap2, FAS, Il6, Adiponectin, Leptin, and Fabp4 in rat HFD-fed obese SD models.

Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes and improved lipid metabolism in the epididymal adipose tissue of HFD-fed obese SD rats via the activation of AMPK-dependent and insulin signaling pathways.

Adiposity and elevated inflammation are two hallmarks of hyperglycemia. However, it is unknown whether clustering of elevated inflammation and adiposity interact act on diabetogenesis and lead to a greater risk for incident type 2 diabetes (T2D).

Adiposity was indicated by body mass index, waist circumference and ultrasonography-measured fatty liver degrees. Elevated inflammation was indicated as high-sensitivity C-reactive protein levels ≥ 2 mg/L. Time-to-event survival analyses were conducted to investigate the joint effect of adiposity and inflammation on incident T2D on both multiplicative and additive scales.

Among 82,172 non-diabetic participants from a prospective cohort in China, 14,278 T2D occurred over a median follow-up of 11 years. In the multivariable-adjusted model, elevated inflammation [1.12 (1.08‒1.16)] and adiposity [1.76 (1.69‒1.83) for overweight/obesity, 1.49 (1.44‒1.55) for central obesity, and 2.02 (1.95‒2.09) for fatty liver] were significantly associated with incident diabetes. Higher adiposity-associated risks and incidence rates of diabetes were observed with elevated inflammation. When studying the joint effect, the adjusted HRs were 1.77 (1.69‒1.85) for overweight/obesity, 1.14 (1.06‒1.23) for elevated inflammation, and 2.08 (1.97‒2.19) for their joint effect, with a relative excess risk due to interaction of 0.17 (0.05‒0.28). The attributable proportions were 71.30% for overweight/obesity, 12.96% for elevated inflammation, and 15.74% for their interaction. Similar results were observed when adiposity was assessed as waist circumference or fatty liver.

Adiposity and elevated inflammation synergically lead to greater risks of incident diabetes than addition of each individual exposure. Strategies simultaneously targeting both risks should produce more benefits for diabetes prevention than through initiatives directed at each separate risk.

The Lymphocyte-to-C-reactive protein ratio (LCR) combines information on immune and inflammatory status. Lymphocytes reflect immune health, while C-reactive protein (CRP) signals systemic inflammation. Some studies have linked LCR with cardiovascular outcomes, suggesting it could help identify at-risk individuals. However, its clinical utility needs further research validation. To investigate the association between lymphocyte-to-C-reactive protein ratio (LCR) and subclinical myocardial injury (SC-MI) in individuals who are free from cardiovascular disease (CVD) within the general population.

The study included individuals in the National Health and Nutrition Examination Survey (NHANES) III. SC-MI was defined as having a Cardiac Infarction Injury Score (CIIS) greater than 10 units on a 12-lead electrocardiogram. Logistic regression models were employed to investigate the association between LCR and SC-MI. In total, 5870 individuals were included in the study, among whom 3266 had a history of SC-MI. Compared with the lowest quartile (Q1) in male, the odds ratios (OR) of SC-MI in Q2, Q3, and Q4 were 0.67 (95%CI: 0.53-0.86), 0.66 (95%CI: 0.51-0.84), and 0.70 (95%CI: 0.55-0.89), respectively. The data shows a trend where the OR of SC-MI are lower in higher quartiles of LCR, compared to the lowest quartile, in the male population (P for trend = 0.006). In other words, the likelihood of SC-MI tends to be lower among males with higher LCR values. However, after adjusting for potential confounding variables, the relationship between LCR and SC-MI displays a pattern of an initial decline, followed by a minor upward shift.

LCR is independently and inversely associated with SC-MI risk in the general population free from CVD. Furthermore, the observed association is exclusive to males, indicating a need for further randomized controlled trials to substantiate the efficacy of implementing LCR reduction as a means of CVD prevention in the male population.

Hyperlipidemia (HLP) is a metabolic syndrome induced by obesity, which has been widely recognized as a significant threat to human health. Pleurotus abieticola, an edible lignin-degrading fungus, remains relatively understudied in terms of its bioactivity and medicinal properties. In this study, the lipid-lowering effect of Pleurotus abieticola polysaccharide (PAPS1) was systematically explored in high-fat diet (HFD)-induced HLP mice. The findings demonstrated that the administration of PAPS1 significantly inhibited bodyweight gain, ameliorated blood glucose and lipid levels, reduced fat accumulation, and mitigated hepatic injury in HLP mice. In addition, PAPS1 demonstrated the capability to increase the levels of three distinct fecal metabolites while simultaneously reducing the levels of eight other fecal metabolites in HLP mice. According to biological detection, PAPS1 reduced the hepatic level of reactive oxygen species (ROS) and pro-inflammatory factors, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, -6, -17A, -22, and -23, and increased the expression of anti-inflammatory factor IL-10. Combined with proteomics, Western blot and immunohistochemistry analysis showed that PAPS1 exerted suppressive effects on inflammation and oxidative damage by inhibiting the nuclear factor-κB (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in HLP mice. These findings offer evidence supporting the effectiveness of PAPS1 as a therapeutic agent in reducing lipid levels through its targeting of chronic inflammation.

The potentiation of synaptic plasticity and serotonin generation by brain-derived neurotrophic factor (BDNF) and tryptophan hydroxylase 2 (TPH2) is well characterized to facilitate rapid and long-lasting antidepressant actions. Therefore, the identification of the key protein that simultaneously controls both BDNF and TPH2 is important for the treatment of depression. We show here that a lack of acetyl-CoA synthetase short-chain family member 2 (ACSS2) causes impairments in BDNF-dependent synaptic plasticity and tryptophan hydroxylase 2 (TPH2)-mediated serotonin generation, thereby contributing to spontaneous and chronic restraint stress (CRS)-induced depressive-like behavior in mice. Conversely, D-mannose is identified as a rapid ACSS2 inducer and thus mediates rapid and long-lasting antidepressant-like effects. Mechanistically, acute and chronic D-mannose administration inhibits the phosphorylation of EF2 to increase BDNF levels and reverse the reduction of TPH2 histone acetylation and transcription. We reveal that ACSS2 promotes TPH2 histone acetylation and transcription with the requirement of AMPK activation. To elevate nuclear ACSS2 levels, D-mannose can rapidly and persistently activate AMPK via Ca2+-CAMKK2 and the lysosomal AXIN-LKB1 pathway to facilitate its fast-acting and persistent antidepressant responses. Taken together, the results presented here reveal that ACSS2 functions as a novel target to link rapid and persistent antidepressant actions and further suggest that D-mannose is a potential therapeutic agent to resist depression through its augmentation of the ACSS2 dependent BDNF and TPH2 pathways.

Chronic consumption of a high-calorie diet compromises the gut microbiota and the integrity of the intestinal wall, which causes translocation of bacterial lipopolysaccharides (LPS) into the blood. This elicits the secretion of pro-inflammatory cytokines, resulting in inflammation. However, how a high-fat high carbohydrate diet affects intestinal permeability and its possible role in the development of prediabetes have not been investigated. This study investigated the effects of HFHC diet-induced prediabetes on gut microbiota and intestinal permeability in male Sprague Dawley rats.

The animals were randomly assigned into the non-prediabetic (NPD) and diet-induced prediabetic (PD) groups (n=6) for 20 weeks. Then, the fecal samples were analyzed to measure the gut microbiota level of Firmicutes, Bacteroidetes, and Proteobacteria in both animal groups. Blood glucose, plasma insulin, serum zonulin, plasma LPS, soluble CD14, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and intestinal fatty-acid binding protein (IFABP) concentrations were measured.

The PD group had a reduction in the Firmicutes and an increase in Bacteroidetes and Proteobacteria levels compared to those in the NPD group. Blood glucose, insulin concentration, serum zonulin, and plasma sCD14 concentrations in the PD group increased significantly, while plasma LPS concentrations were similar to the NPD group. Concentrations of plasma TNF-α, IL-6, CRP, and IFABP, an intracellular protein expressed in the intestine, increased in PD compared to the NPD group.

the study results cumulatively suggest that chronic consumption of the HFHC diet may be associated with the dysregulation of gut microbiota, leading to increased intestinal permeability.

Systemic inflammation is a root cause of lifestyle-related chronic diseases and may also play a role in the development and progression of osteoarthritis (OA). Lifestyle medicine seeks to treat, prevent, and reverse lifestyle-related chronic disease via 6 pillars: nutrition, sleep health, stress management, physical activity, social connections, and risky behavior avoidance/reduction. This article presents a review of the literature in which we assess the connections between the 6 pillars of lifestyle medicine, chronic systemic inflammation, and OA. We also discuss the whole-person approach that lifestyle medicine interventions can provide to reduce chronic systemic inflammation and affect the development or progression of OA.

Multicellular organisms live in environments containing diverse nutrients and a wide variety of microbial communities. On the one hand, the immune response of organisms can protect from the intrusion of exogenous microorganisms. On the other hand, the dynamic coordination of anabolism and catabolism of organisms is a necessary factor for growth and reproduction. Since the production of an immune response is an energy-intensive process, the activation of immune cells is accompanied by metabolic transformations that enable the rapid production of ATP and new biomolecules. In insects, the coordination of immunity and metabolism is the basis for insects to cope with environmental challenges and ensure normal growth, development and reproduction. During the activation of insect immune tissues by pathogenic microorganisms, not only the utilization of organic resources can be enhanced, but also the activated immune cells can usurp the nutrients of non-immune tissues by generating signals. At the same time, insects also have symbiotic bacteria in their body, which can affect insect physiology through immune-metabolic regulation. This paper reviews the research progress of insect immune-metabolism regulation from the perspective of insect tissues, such as fat body, gut and hemocytes. The effects of microorganisms (pathogenic bacteria/non-pathogenic bacteria) and parasitoids on immune-metabolism were elaborated here, which provide guidance to uncover immunometabolism mechanisms in insects and mammals. This work also provides insights to utilize immune-metabolism for the formulation of pest control strategies.

Sex and reproductive status of the host have a major impact on the immune response against infection. Our aim was to understand their impact on host tolerance or resistance in the systemic Mycobacterium marinum infection of Drosophila melanogaster. We measured host survival and bacillary load at time of death, as well as expression by quantitative real-time polymerase chain reaction of immune genes (diptericin and drosomycin). We also assessed the impact of metabolic and hormonal regulation in the protection against infection by measuring expression of upd3, impl2 and ecR. Our data showed increased resistance in actively mating flies and in mated females, while reducing their tolerance to infection. Data suggests that Toll and immune deficiency (Imd) pathways determine tolerance and resistance, respectively, while higher basal levels of ecR favours the stimulation of the Imd pathway. A dual role has been found for upd3 expression, linked to increased/decreased mycobacterial load at the beginning and later in infection, respectively. Finally, impl2 expression has been related to increased resistance in non-actively mating males. These results allow further assessment on the differences between sexes and highlights the role of the reproductive status in D. melanogaster to face infections, demonstrating their importance to determine resistance and tolerance against M. marinum infection.

To investigate the association of body mass index (BMI) with asthma and analyze the risk factors of asthma persistence among overweight/obese adolescents and those with a high risk for obesity.

In this cross-sectional study, adolescents aged 11-17 years with complete general information and asthma diagnoses were selected from the National Health and Nutrition Examination Survey database. For adolescents without self-reported asthma, we performed matching according to age and sex at a case-to-control ratio of 1:3. Logistic regression analysis was employed to identify independent predictors of asthma occurrence followed by constructing a nomogram and comparing its efficacy to independent factors in predicting asthma occurrence. Besides, associations of BMI with asthma occurrence and persistence were evaluated. Finally, we obtained risk factors for asthma persistence in overweight/obese individuals and those at a high risk for obesity.

Totally 753 adolescents with asthma and 2259 adolescents without asthma were included to analyze the occurrence of asthma. BMI and Hispanic Ethnicity were independent predictors of asthma occurrence and were included in nomogram construction. BMI had an efficiency comparable to that of the nomogram model in predicting asthma occurrence, which is superior to that of Hispanic Ethnicity. Of the 753 adolescents diagnosed with asthma, 464 were still diagnosed with asthma of at least a year's duration. Interestingly, BMI may have the ability to predict asthma persistence. Further, Hispanic Ethnicity and household income were significantly related to asthma occurrence among overweight/obese and high-risk obese individuals.

High BMI could independently predict increased asthma occurrence. Additionally, BMI may play an essential role in predicting asthma persistence. This study may help improve the diagnosis and reduce the occurrence of asthma.

Macrophages are considered an essential source of inflammatory cytokines, which play a pivotal role in the development of diabetes and its sequent complications. Therefore, a better understanding of the intersection between the development of diabetes and macrophage is of massive importance.

In this study, we performed an informative bibliometric analysis to enlighten relevant research directions, provide valuable metrics for financing decisions, and help academics to gain a quick understanding of the current macrophage-related diabetes studies knowledge domain.

The Web of Science Core Collection database was used for literature retrieval and dataset export. Bibliometrix R-package was performed to conduct raw data screening, calculating, and visualizing.

Between 2000 and 2022, the annual publication and citation trends steadily increased. Wu Yonggui was the scholar with the most published papers in this field. The institute with the highest number of published papers was the University of Michigan. The most robust academic collaboration was observed between China and the United States of America. Diabetologia was the journal that published the most relevant publications. The author's keywords with the highest occurrences were "inflammation", "diabetic nephropathy", and "obesity". In addition, "Macrophage polarization" was the current motor topic with potential research prospects.

These comprehensive and visualized bibliometric results summarized the significant findings in macrophage-related diabetes studies over the past 20 years. It would enlighten subsequent studies from a macro viewpoint and is also expected to strengthen investment policies in future macrophage-related diabetes studies.