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Immune cell changes in response to obesity in adipose tissue Lean adipose is dominated by alternatively activated M2 macrophages, Th2 cells, Tregs, iNKT cells, and eosinophils, while obese adipose has increased influx of monocytes, proinflammatory M1 macrophages, Th1 cells, Th17 cells, neutrophils, and B cells. Created with Biorender.com.
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The global obesity epidemic is a major contributor to chronic disease and disability in the world today. Since the discovery of leptin in 1994, a multitude of studies have characterized the pathological changes that occur within adipose tissue in the obese state. One significant change is the dysregulation of adipokine production. Adipokines are an...
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... If the patients with diabetes also suffer from obesity, the adipocytes secrete an excessive amount of adipokines, in addition to the pre-existing ones. There are already comprehensive data about the effects of adiponectin, leptin, resistin and visfatin in diabetes mellitus [22][23][24]. ...
It is widely known that diabetes mellitus negatively impacts both the innate immunity (the inflammatory response) and the acquired immunity (the humoral and cellular immune responses). Many patients with diabetes go on to develop chronic kidney disease, which will necessitate hemodialysis. In turn, long-term chronic hemodialysis generates an additional chronic inflammatory response and impairs acquired immunity. The purpose of this paper is to outline and compare the mechanisms that are the basis of the constant aggression towards self-components that affects patients with diabetes on hemodialysis, in order to find possible new therapeutic ways to improve the functionality of the immune system. Our study will take a detailed look at the mechanisms of endothelial alteration in diabetes and hemodialysis, at the mechanisms of inflammatory generation and signaling at different levels and also at the mechanisms of inflammation-induced insulin resistance. It will also discuss the alterations in leukocyte chemotaxis, antigen recognition and the dysfunctionalities in neutrophils and macrophages. Regarding acquired immunity, we will outline the behavioral alterations of T and B lymphocytes induced by diabetes mellitus and chronic hemodialysis.
... For example, IL-6 that is released by muscle during the exercise and has lipolytic and fatty acid oxidation effects [19]. An adipokine has its negative side when released by an adipose tissue that induces an inflammation, however in other situation body becomes anti-inflammatory when this adipokine is released by muscles during the mass [26]. IL-15 was linked to muscle growth and also the process of 'browning' of white fat where the white fat is converted into active brown fat through this mechanism. ...
Previously regarded as a movement and posture control agent, the skeletal muscle is now recognized as an endocrine organ that may affect systemic inflammation and metabolic health. The discovery of myokines such as IL-6, released from skeletal muscle in response to physical exercise, is now one of the most recent insights. Myokines are the mediators of the balance between the pro-inflammatory and anti-inflammatory responses. This underscores the muscle function as a determinant of good health and prevention of diseases. Advances in ultrasound technology improved evaluation of muscle thickness, composition, and determining fat distribution. Combining imaging with molecular biology, researchers discovered the complicated interplay between muscle function, cytokine production and general health effects.The production of myokines with exercise showcasing the adaptability of muscles to high-stress conditions and contributing to metabolism and inflammation regulation. These findings have significant implications in order to provide improvement in metabolic and inflammatory diseases.
... Thus, BMI may serve as a mediator linking diet, persistent low-grade inflammation, and inflammation-related diseases, going beyond being just a confounding factor. The accumulation of body fat creates an inflammatory metabolic milieu, with BMI showing a positive correlation with inflammatory indicators (50,51). It is plausible that the interaction mechanism associating CDAI with stroke relates to the link between inflammation and atherosclerosis. ...
Background
This cross-sectional study aims to explore the interactive effects of the Composite Dietary Antioxidant Index (CDAI) and Body Mass Index (BMI) on stroke risk among U.S. adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2018.
Methods
The analysis involved 42,042 participants from a representative sample of non-institutionalized U.S. civilians, selected through a stratified, multistage probability sampling method. Dietary intake data were collected over two 24-h periods using the Automated Multiple-Pass Method. The study calculated a modified CDAI to assess dietary antioxidant intake, excluding supplements and water sources. Statistical methods included multivariable logistic regression and Generalized Additive Models (GAM) to evaluate the interaction between CDAI scores and BMI in relation to stroke risk, adjusting for a wide range of demographic, lifestyle, and health covariates.
Results
The research identified a significant interaction between CDAI scores and BMI categories in stroke risk assessment. While a negative correlation was observed between CDAI scores and stroke risk across the total population (OR 0.97, 95% CI 0.96–0.99), this relationship varied notably across different BMI groups. In participants with a BMI ≥25, a statistically significant negative association persisted, displaying a non-linear pattern. The study also revealed an inflection point in the CDAI score, indicating a shift in the relationship between dietary antioxidants and stroke risk.
Conclusion
This study underscores the complex interaction between dietary antioxidant intake and BMI in determining stroke risk among U.S. adults. The findings suggest that individuals with higher BMI may experience more pronounced benefits from dietary antioxidants in stroke prevention. These insights could inform targeted dietary recommendations and public health strategies aimed at reducing stroke risk, particularly in populations with higher BMI. Further research is needed to fully understand these interactions and their implications for stroke prevention guidelines.
... Adipokines are cytokines secreted by adipose tissue and play a role in immune regulation [50]. Altered levels of adiponectin (ADP) and leptin have been reported in patients with migraine. ...
Background
The pathogenesis of migraine remains unclear; however, a large body of evidence supports the hypothesis that immunological mechanisms play a key role. Therefore, we aimed to review current studies on altered immunity in individuals with migraine during and outside attacks.
Methods
We searched the PubMed database to investigate immunological changes in patients with migraine. We then added other relevant articles on altered immunity in migraine to our search.
Results
Database screening identified 1,102 articles, of which 41 were selected. We added another 104 relevant articles. We found studies reporting elevated interictal levels of some proinflammatory cytokines, including IL-6 and TNF-α. Anti-inflammatory cytokines showed various findings, such as increased TGF-β and decreased IL-10. Other changes in humoral immunity included increased levels of chemokines, adhesion molecules, and matrix metalloproteinases; activation of the complement system; and increased IgM and IgA. Changes in cellular immunity included an increase in T helper cells, decreased cytotoxic T cells, decreased regulatory T cells, and an increase in a subset of natural killer cells. A significant comorbidity of autoimmune and allergic diseases with migraine was observed.
Conclusions
Our review summarizes the findings regarding altered humoral and cellular immunological findings in human migraine. We highlight the possible involvement of immunological mechanisms in the pathogenesis of migraine. However, further studies are needed to expand our knowledge of the exact role of immunological mechanisms in migraine pathogenesis.
... In both industrialized and developing countries, obesity has been related to MS, where individuals with MS have a higher risk of developing cardiovascular diseases and type 2 diabetes (1,18). These metabolic disorders are, in part, linked to adipose tissue secretions, collectively known as adipokines (19), and low-level chronic inflammation. Our results showed that at 60 days of age rats from the SL group were obese, normoglycemic, hypoinsulinemic, and presented higher concentrations of IL-6 and IL-10, pro-and anti-inflammatory cytokines, respectively, which can be collectively translated as metabolic disturbance. ...
Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.
... McP-1 is a member of the McP family consisting of at least four members (McP-1, -2, -3, -4) and it exerts its action by binding to its chemokine receptor, c-c motif chemokine receptor 2 (ccr2), which is a CC motif receptor (51). The CCR2A isoform is expressed by mononuclear cells and vascular smooth muscle cells (VSMCs), while CCR2B is expressed by monocytes and natural killer cells (52). McP-1 plays a role in the recruitment, migration and infiltration of monocytes, microglia and memory T lymphocytes to sites of infection and injury (53-56). ...
... McP-1 plays a role in the recruitment, migration and infiltration of monocytes, microglia and memory T lymphocytes to sites of infection and injury (53-56). MCP-1 is secreted predominately by macrophages and endothelial cells (52). In the adipose tissue of lean subjects, most resident macrophages are polarized to the M2 anti-inflammatory phenotype, contributing to insulin sensitivity, with the secretion of (a) anti-inflammatory cytokines, such as IL-4, IL-10, IL-11, IL-13 and IL-1Ra, and (b) anti-inflammatory adipokines, such as adiponectin and apelin. ...
... There is a close relationship between McP-1 and the number of resident macrophages in adipocytes (57)(58)(59). Plasma levels of MCP-1 are markedly elevated in obesity and T2DM (52,58,(60)(61)(62)(63). in obesity, the production of McP-1 by adipocytes results in recruitment of monocytes and activation of macrophages, which causes AT inflammation (56,64). It has been suggested that obesity-associated inflammation in WAT is the causal factor of systemic ir (65). in addition, serum McP-1 levels are higher in patients with atherosclerosis and the expression of mrna MPc-1 is increased in atherosclerotic lesions as well (66)(67)(68). ...
Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co-morbidities, including type-2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular diseases, non-alcoholic fatty liver disease, kidney diseases, respiratory disorders, sleep apnea, musculoskeletal disorders and osteoarthritis, subfertility, psychosocial problems and certain types of cancers. The underlying inflammatory mechanisms interconnecting obesity with metabolic dysfunction are not completely understood. Increased adiposity promotes pro-inflammatory polarization of macrophages toward the M1 phenotype, in adipose tissue (AT), with subsequent increased production of pro-inflammatory cytokines and adipokines, inducing therefore an overall, systemic, low-grade inflammation, which contributes to metabolic syndrome (MetS), insulin resistance (IR) and T2DM. Targeting inflammatory mediators could be alternative therapies to treat obesity, but their safety and efficacy remains to be studied further and confirmed in future clinical trials. The present review highlights the molecular and pathophysiological mechanisms by which the chronic low-grade inflammation in AT and the production of reactive oxygen species lead to MetS, IR and T2DM. In addition, focus is given on the role of anti-inflammatory agents, in the resolution of chronic inflammation, through the blockade of chemotactic factors, such as monocytes chemotractant protein-1, and/or the blockade of pro-inflammatory mediators, such as IL-1β, ΤΝF-α, visfatin, and plasminogen activator inhibitor-1, and/or the increased synthesis of adipokines, such as adiponectin and apelin, in obesity-associated metabolic dysfunction.
... Adipsin levels were found in higher concentrations in autoimmune diseases. However, further studies are needed to assess the association of adipsin with SLE [18]. ...
Metabolic syndrome (MetS) is a group of physiological abnormalities characterized by obesity, insulin resistance (IR), and hypertriglyceridemia, which carry the risk of developing cardiovascular disease (CVD) and type 2 diabetes (T2D). Immune and metabolic alterations have been observed in MetS and are associated with autoimmune development. Systemic lupus erythematosus (SLE) is an autoimmune disease caused by a complex interaction of environmental, hormonal, and genetic factors and hyperactivation of immune cells. Patients with SLE have a high prevalence of MetS, in which elevated CVD is observed. Among the efforts of multidisciplinary healthcare teams to make an early diagnosis, a wide variety of factors have been considered and associated with the generation of biomarkers. This review aimed to elucidate some primary biomarkers and propose a set of assessments to improve the projection of the diagnosis and evolution of patients. These biomarkers include metabolic profiles, cytokines, cardiovascular tests, and microRNAs (miRs), which have been observed to be dysregulated in these patients and associated with outcomes.
... An increased LAR value is an early indicator of adipose tissue dysfunction associated with an increase in insulin resistance, type 2 diabetes mellitus, and cardiovascular diseases. The imbalance between anti-inflammatory and pro-inflammatory adipokines contributes to vascular and endothelial dysfunction, immune cell infiltration, local and systemic inflammation [7,20], and manifestation of metabolic disorders [7,21,22]. So far, changes in adipokine pattern have been observed in plasma of individuals with obesity and diabetes, including GDM [7-9,23-26]. ...
Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin–adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring’s metabolic homeostasis.
... The profile of adipokines produced by different adipose tissue depots reflects their health status [97]. WAT from lean subjects releases an anti-inflammatory adipokine profile with high levels of adiponectin, IL-10, and IL-4 and low levels of leptin, TNF-α, IL-6, and MCP-1, while the WAT from obese releases the same adipokines but in inverse proportion [98]. Interestingly, high-fructose intake has also been associated with damaged adipokine profile secretion [72]. ...
Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.
... Existing literature supports that obesity accompanied by MetDys is associated with low-grade chronic inflammation and perturbed metabolic hormones and adipokines. 16 The current study found that the MetDys group exhibited elevated levels of known cardiometabolic disease biomarkers such as CRP, insulin, and lactate dehydrogenase. The current study also noted significant elevation in circulating levels of leptin in the MetDys group, supporting the general ...
... This is a PDF file of an article accepted, but it is not yet the definitive version of record. 16 including those related to bacterial metabolism, morphology and growth, were reduced in the MetDys group, the pore-forming toxin thiol-activated cytolysin and the phospholipid cleaving enzyme phospholipase C demonstrated marked increases in abundance. Interestingly, while there are few reports detailing the role of microbial phospholipase C in health and disease, phospholipase A2 has received attention as an immune modulator and promotor of inflammatory pathways. ...
Background
The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys).
Methods
This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m²) and males with evidence of MetDys (n=14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m²) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis.
Results
In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups.
Conclusion
These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease.
