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Serum levels of IL-12 in obese and nonobese individuals. Circulating levels of IL-12 (a) were assessed in normal weight, overweight, and obese subjects, according to the World Health Organization criteria for body mass index (BMI). In the study population, serum concentrations of IL-12 (b) were also evaluated in terms of abdominal obesity. Serum IL-12 was elevated in overweight and obese individuals, as well as in subjects exhibiting abdominal obesity. For women, abdominal obesity was considered when the waist measurement was 88 cm or higher, whereas for men, it was considered when the waist measurement was 102 cm or higher. Data are expressed as median and interquartile range in a box plot analysis. The mean value of IL-12 is graphically showed in a red asterisk. Differences were considered significant when P<0.05. ‡P<0.0001.
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Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammat...
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Citations
... Furthermore, analysis of supernatants from sort-purified WAT cDC1, cDC2 and macrophage populations from HFD-fed mice suggested that only WAT cDC1s secreted IL-12p70 by reports have demonstrated that IL-12 stimulates IFN-γ production by WAT group 1 ILCs during obesity to drive WAT inflammation and systemic metabolic dysfunction 14,17 . In support of these findings, IL-12 signalling has been linked with the development of obesity-associated inflammation and metabolic dysfunction in mice, and serum IL-12 levels are increased in individuals with obesity compared with lean individuals 17,[22][23][24][25] . However, the mechanisms that drive IL-12 production as well as the precise cellular sources of IL-12 in the WAT during obesity remain unknown. ...
Obesity is associated with chronic low-grade white adipose tissue (WAT) inflammation that can contribute to the development of insulin resistance in mammals. Previous studies have identified interleukin (IL)-12 as a critical upstream regulator of WAT inflammation and metabolic dysfunction during obesity. However, the cell types and mechanisms that initiate WAT IL-12 production remain unclear. Here we show that conventional type 1 dendritic cells (cDC1s) are the cellular source of WAT IL-12 during obesity through analysis of mouse and human WAT single-cell transcriptomic datasets, IL-12 reporter mice and IL-12p70 protein levels by enzyme-linked immunosorbent assay. We demonstrate that cDC1s contribute to obesity-associated inflammation by increasing group 1 innate lymphocyte interferon-γ production and inflammatory macrophage accumulation. Inducible depletion of cDC1s increased WAT insulin sensitivity and systemic glucose tolerance during diet-induced obesity. Mechanistically, endocytosis of apoptotic bodies containing self-DNA by WAT cDC1s drives stimulator of interferon genes (STING)-dependent IL-12 production. Together, these results suggest that WAT cDC1s act as critical regulators of adipose tissue inflammation and metabolic dysfunction during obesity.
... Suárez Álvarez et al. [33] found that IL-12 levels were pointedly higher in overweight and obese individuals compared to the control group. Nikolaju et al. [34] indicated that there was a statistically significant positive correlation between IL-12 levels and total cholesterol levels in overweight and obese women. ...
Purpose Obesity is a medical condition caused by excess body fat that accumulates at a level that can have a negative impact on health. Altered glucose and lipid metabolism, low-grade chronic inflammation play a role in the pathogenesis of obesity and obesity-related metabolic dysfunction. In our study, we aimed to determine the apelin, kynurenine, IL-4/IL-10/IL-12/TNF-α protein levels in obese individuals and healthy control groups, and to investigate the possible relationship between clinical parameters with the data to be obtained. Materials and Methods The levels of Apelin, Kynurenine, IL-4/IL-10/IL-12/TNF-α in serum/plasma samples were measured with enzyme-linked immunosorbent assay. Absorbance of the samples were measured on a microplate reader spectrophotometrically at a wavelength of 450 nm. Results The levels of Kinurenin, IL-4, and IL-12 in the serum were higher in control group than in obese patients (p=0.009, p=0.004, p=0.002, respectively). There was no significant difference between the control and obese patients in TNF-α, IL-10 and Apelin levels (p=0.277, p=0.711, p=0.472, respectively). Conclusion Inflammation and altered immune response are two important components of obesity. They play a major role in the formation of metabolic diseases associated with obesity. Changes in adipokine levels may lead to the development and maintenance of insulin resistance and systemic inflammation in obesity. The results demonstrate that kynurenine, IL-4, and IL-12 have a complex role in obesity and can be used as therapeutic targets.
... Wieder-Huszla et al. [15] reported lower 25-OH vitamin D levels in Type 2 diabetic patients than in non-diabetic people. A study by Suárez-Álvarez et al. [16] in Mexico investigated the relationship between obesity-related parameters and the inflammatory marker IL-12 and reported that IL-12 levels were increased in the overweight and obese, thereby establishing a relationship of IL-12 with inflammation and obesity markers. Nikołajuk et al. [17] examined the association between IL-12 levels and lipid parameters in overweight and obese women, and established a statistically significant positive correlation between IL-12 levels and total cholesterol levels among such patients (r=0.32, ...
... IL-6 acts synergistically with other interleukins and growth factor and enhances circulating platelet count [4]. Similarly IL-12, another proinflammatory cytokine has received increasing attention in the development of obesity related disorders [5]. ...
... The present study demonstrates that circulating levels of IL-12 has a strong relationship with obesity and other parameters of metabolic risk like hypertriglyceridaemia, hyperfibrinogenaemia and sCD40L. Study by Suarez-Alvarez K et al., has also shown that IL-12 has a strong positive relationship with systemic low grade inflammation and obesity related markers [5]. Comparable findings were also reported by Mohamed AA et al., where it was observed that there is increased secretion of proinflammatory cytokines like IL-12 in obese subjects in comparison to normal weight control group [32]. ...
Introduction: Obesity is the established risk factor for the
development of cardiovascular diseases like hypertension, diabetes
mellitus, chronic heart diseases and atrial fibrillation. Cytokines
such as Interleukin-6 and Interleukin-12 (IL-6, IL-12) play a
significant role in the development of obesity related disorders.
Cluster of differentiation 40 (CD40) ligand, a trimetric protein
structurally related to Tumour Necrosis Factor alpha (TNF-α)
family contributes to atherothrombosis by being a link between
platelets, inflammation, thrombosis and atherogenesis. The present
study was undertaken to explore the interplay between inflammatory
cytokines and CD40 Ligand (CD40L) in young obese tribal
subjects.
Aim: To estimate the level of proinflammatory cytokines like
IL-6, IL-12 and CD40 ligand in obese subjects and compare
with non obese tribal subjects of Tripura, India.
Materials and Methods: In this observational study, 60 non
obese and 60 young obese tribal subjects within age group of
18-36 years were enrolled, over a period of two years from March
2014 to March 2016 at Tripura Medical College (TMC) and Dr.
BRAM Teaching Hospital, Tripura, India. Serum levels of IL-6,
IL-12 and C-reactive Protein (CRP) were estimated by EnzymeLinked Immunoassay (ELISA). Plasma level of fibrinogen activity
was measured by coagulation assay. The Homeostasis Model
Assessment (HOMA) of insulin resistance was calculated as
insulin (micro unit per milliliter) x glucose (milimoles/Ltr)/22.5.
Soluble Cluster of differentiation 40 Ligand (sCD40L) in serum was
determined by ELISA. Statistical analysis was performed using
Mann-Whitney test, Chi-square test and regression analysis.
Results: Cohort consisted of 19 (31.1%) males and 41 (68.3%)
females whereas the control non obese group comprised of
16 (26.6%) males and 44 (73.3%) females. In the present study,
the authors had observed that the biochemical parameters
like fasting blood glucose, cholesterol, triglycerides and HighDensity Lipoprotein (HDL) cholesterol were significantly higher
in obese subjects compared to non obese subjects. Further, the
authors observed that CRP, IL-6, IL-12 and fibrinogen level were
statistically higher in obese subjects. A statistical significant
difference was found in fasting insulin level and Homeostasis
Model Assessment of Insulin Resistance (HOMA-IR) between
obese and the non obese group. Finally, there was positive
relationship between CD40 ligand and cytokines with obesity.
Conclusion: The present study has demonstrated that the
circulating levels of IL-6 and IL-12 have a strong relationship
with obesity and other parameters of metabolic risk. It was also
observed that there is a clear positive relationship between CD40L and cytokine families.
... Wieder-Huszla et al. [15] reported lower 25-OH vitamin D levels in Type 2 diabetic patients than in non-diabetic people. A study by Suárez-Álvarez et al. [16] in Mexico investigated the relationship between obesity-related parameters and the inflammatory marker IL-12 and reported that IL-12 levels were increased in the overweight and obese, thereby establishing a relationship of IL-12 with inflammation and obesity markers. Nikołajuk et al. [17] examined the association between IL-12 levels and lipid parameters in overweight and obese women, and established a statistically significant positive correlation between IL-12 levels and total cholesterol levels among such patients (r=0.32, ...
... IL-12 is secreted by NK cells, monocytes, and macrophages and is an important factor in T-helper type 1 generation and early inflammation responses [104]. Increased IL-12 appears linked to pathogenesis of autoimmune diseases such as arthritis, multiple sclerosis, and insulin dependent diabetes [105]. IL-12 has a critical role during obesity-related IR (Fig. 1) in which it increases epididymis adipose tissue and adipose pro-inflammatory macrophages [40,106]. ...
The increasing prevalence of obesity and the associated morbidity and mortality are important public health problems globally. There is an important relationship between an unhealthy lifestyle and increased serum inflammatory cytokines. Adipocytes secrete several pro-inflammatory cytokines involved in the recruitment and activation of macrophages resulting in chronic low-grade inflammation. Increased cytokines in obese individual are related to the progression of several disorders including cardiovascular disease, hypertension, and insulin resistance. In present review we have summarized the crucial roles of cytokines and their inflammatory functions in obesity-related immune disorders.
... The overexpression of proinflammatory cytokines is considered to be the link between obesity-induced inflammation and endothelial dysfunction [15]. In this sense, TNF-α has received considerable attention as one of the key mediators of inflammation involved in obesity and is found in high concentrations in subjects with obesity than in lean [7,18,19]. Also increased AT expression of TNF-α has been reported [20]. Our results came in concordance with the literature and other previous studies regarding TNF-α levels in class II and III obesity groups. ...
... p40 might have an independent role in initiating the immune response [34]. This heterodimeric class I helical cytokine is mainly produced by dendritic cells (DCs) and macrophages, and influences differentiation of T helper 1 (Th1) immune cells [19]. In the context of immune cells interaction in AT in obesity, Liu and Nikolajczyk [16] indicated that obese AT exhibited a shift in macrophage polarization from a simplistically designated anti-inflammatory M2-like (F4/80−) to a pro-inflammatory M1-like (F4/8+) macrophage phenotype, the latter is considered a main contributor to AT inflammation in obesity. ...
... Along with our results, the study of obesity in the Mexican adult population revealed that, overweight and subjects with obesity (21 women with BMI ≥ 30 kg/m 2 ) had higher levels of IL-12 than a normal-weight group. Additionally, serum levels of IL-12 correlated with systemic low-grade inflammation, BMI and the grade of abdominal obesity [19]. IL-12 could be involved in the development of obesity-associated co-morbidities, especially atherosclerosis. ...
Background:
Obesity is an alarming threat to health in Egypt. More than one in three Egyptians is obese, the highest rate in the world. We aimed to delineate the variability of inflammation and endothelial dysfunction markers among Egyptian females with different obesity classes.
Methods:
Out of 130 females, 70 were categorized into three obesity groups: Class I, body mass index (BMI) 30-34.9 kg/m2; Class II, BMI 35-39.9 kg/m2 and Class III BMI ≥ 40 kg/m2, besides 60 control subjects. Anthropometric measurements were recorded and serum levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin (IL) 6 (IL-6), IL-12, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1) were assessed among participants.
Results:
In all three classes of obesity, significant increase (P <0.05) in BMI, waist-hip ratio, fat mass and body fat mass % were noted. CRP and sVCAM-1 levels were increased among the three obesity groups. TNF-α levels were increased in class II and III obesity groups. IL-6 and IL-12 levels were elevated in class I and class III groups. While, ICAM-1 levels were increased in class III obesity group.
Conclusion:
Based on individuals' BMI, serum levels of TNF-α, CRP, IL-6, IL-12, sVCAM-1 and sICAM-1 are differentially altered with the progression of obesity. We strongly support the hypothesis that, as the obesity rate is still mounting, a subclinical inflammatory reaction has a role in pathogenesis of obesity and emphasize the elevation of endothelial dysfunction in individuals with obesity.
... A correlation was found between IL-12 and obesity. Serum IL-12 was remarkably higher in overweight and obese individuals than in normal weight controls as indicated by a clinical study [51]. Proinflammatory cytokines such as IL-12 may play role in mediating insulin response, and elevated IL-12 is involved in the development of obesity-induced insulin resistance [52]. ...
Mechanisms underlying human diseases have been revealed with the development of molecular biology. The underlying molecular basis of disorders is valuable in prevention, diagnosis, and treatment. Decade-long efforts have been devoted to investigating disease–gene association through positional cloning of disease genes and genome-wide association studies. In particular, correlations among different diseases have been discovered by many clinical cases. The shared disease-associated genes may help reveal the intrinsic relationship in the genetic level, provide an access to evaluate disease similarity, and establish a human disease network. Although many methods have been proposed to measure disease similarity, they only consider the genes or functions directly annotated to diseases but ignore the interactions among genes or functions. These interactions cause deficiency in disease classification. Basing on network-based disease module, we presented a systematic research to further investigate the relationship among different human diseases and explore whether this correlation depends on the functions of corresponding disease genes. On the one hand, a disease clustering based on the separation score between diseases is applied to divide 299 diseases into 15 relatively separated disease clusters. On the other hand, an optimal clustering scheme discriminating 15 disease clusters was learned based on disease-associated genes, their GO terms, and KEGG pathways annotations. The detected key signatures showed the highest relevance to distinguishing distinct disease clusters and represented the essential functions in corresponding pathogenesis. This study provides a novel approach to predict the network and function characteristics and reveals the functional essence of diseases.
... Instead, it is well established that IL-12 and STAT4 signaling are critical for NK cells to produce IFN-γ and proliferate following viral infection [109,110] and elevated IL-12 transcripts are found in the adipose tissues of mice soon after HFD feeding [14,111,112]. In support of these findings in mice, clinical studies have observed higher serum levels of IL-12 in obese individuals compared to lean individuals [113,114]. A recent study also demonstrated that IL-12 is induced as early as 3 weeks after HFD administration in the VAT and SAT, and IL-12 signaling is an absolute requirement for driving the proliferation and accumulation of group 1 ILCs in the adipose tissue during diet-induced obesity [14]. ...
Innate lymphoid cells (ILCs) are tissue-resident sentinels of the immune system that function to protect local tissue microenvironments against pathogens and maintain homeostasis. However, because ILCs are sensitively tuned to perturbations within tissues, they can also contribute to host pathology when critical activating signals become dysregulated. Recent work has demonstrated that the crosstalk between ILCs and their environment has a significant impact on host metabolism in health and disease. In this review, we summarize studies that support evidence for the ability of ILCs to influence tissue and systemic metabolism, as well as how ILCs can be regulated by environmental changes in systemic host metabolism. We also highlight studies demonstrating how ILC- intrinsic metabolism influences their activation, proliferation, and homeostasis. Finally, this review discusses the challenges and open questions in the rapidly expanding field of ILCs and immunometabolism.
... We identified IL-12 as a cytokine that is most affected by Acly inhibition and that is highly sensitive to perturbations of glucose metabolism. Indeed, IL-12 serum concentrations associate with diabetes and are increased in sera of patients with type I and type II diabetes and metabolic syndrome (Schmidt et al., 2015;Suá rez-Á lvarez et al., 2013;Winkler et al., 1998;Wegner et al., 2008). In light of these findings, future investigations should be directed to determine, for example, how high blood glucose or chronic hyperglycemia affects the epigenetic landscape of macrophages in vivo. ...
Toll-like receptor (TLR) activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades. Whether concurrent changes in the cellular metabolism that occur upon TLR activation influence the quality of the transcriptional responses remains unknown. Here, we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction. Shortly after TLR4 activation, macrophages increased glycolysis and tricarboxylic acid (TCA) cycle volume. Metabolic tracing studies revealed that TLR signaling redirected metabolic fluxes to generate acetyl-Coenzyme A (CoA) from glucose resulting in augmented histone acetylation. Signaling through the adaptor proteins MyD88 and TRIF resulted in activation of ATP-citrate lyase, which in turn facilitated the induction of distinct LPS-inducible gene sets. We postulate that metabolic licensing of histone acetylation provides another layer of control that serves to fine-tune transcriptional responses downstream of TLR activation. Our work highlights the potential of targeting the metabolic-epigenetic axis in inflammatory settings.
