Development Of Chronic Low-grade Inflammation Research Articles

Pathogenetic Mechanisms of the Relationship Between Osteoarthritis and Intestinal Dysbiosis

The potential association between dysbiosis of the gut microbiota and osteoarthritis is confirming by a growing number of studies. Given the social significance, the high prevalence of osteoarthritis, and evidences that quantitative and qualitative modification of the gut microbiota affects its progression, it seems important to clarify the underlying mechanisms of this association. Osteoarthritis is a multifactorial joint disease, which is based primarily on the progressive degeneration of articular cartilage. Impaired metabolic activity of chondrocytes, consisting in an imbalance in the extracellular matrix synthesis and degradation processes, causes the persistent release of molecular patterns associated with damage. This leads to the activation of a wide range of innate immune cells receptors and is the basis for the development of an inflammatory reaction in the joint. The involvement of macrophages in the synovial membrane and their activation leads to the production of pro-inflammatory cytokines, leading to the development of chronic low-grade inflammation in the joint, supporting the synthesis of catabolic enzymes by chondrocytes and escalating the cartilage degeneration. Microbial dysbiosis, defined as an adverse modification in the diversity, structure, or metabolic activity of the gut microbiota, is a hidden risk factor, accompanied by metabolic endotoxemia and, consequently, by increased production of pro-inflammatory cytokines, that support the systematic low-grade inflammation and pathophysiological mechanisms of osteoarthritis. It has been shown that dysbiosis of the gut microbiota intestinal takes part in the formation of other osteoarthritis risk factors for, for example, obesity and metabolic disorders. The identification of important interrelated pathophysiological mechanisms of these pathologies will contribute to the development of new pathogenetic treatment methods with their subsequent active introduction into clinical practice.

Obesity-mediated Lipoinflammation Modulates Food Reward Responses.

Accumulation of white adipose tissue (WAT) during obesity is associated with the development of chronic low-grade inflammation, a biological process known as lipoinflammation. Systemic and central lipoinflammation accumulates pro-inflammatory cytokines including IL-6, IL-1β and TNF-α in plasma and also in brain, disrupting neurometabolism and cognitive behavior. Obesity-mediated lipoinflammation has been reported in brain regions of the mesocorticolimbic reward circuit leading to alterations in the perception and consumption of ultra-processed foods. While still under investigation, lipoinflammation targets two major outcomes of the mesocorticolimbic circuit during food reward: perception and motivation ("Wanting") and the pleasurable feeling of feeding ("Liking"). This review will provide experimental and clinical evidence supporting the contribution of obesity- or overnutrition-related lipoinflammation affecting the mesocorticolimbic reward circuit and enhancing food reward responses. We will also address neuroanatomical targets of inflammatory profiles that modulate food reward responses during obesity and describe potential cellular and molecular mechanisms of overnutrition linked to addiction-like behavior favored by brain lipoinflammation.

Unraveling the Role of Adiponectin Receptors in Obesity-Related Breast Cancer.

Obesity has a noteworthy role in breast tumor initiation and progression. Among the mechanisms proposed, the most validated is the development of chronic low-grade inflammation, supported by immune cell infiltration along with dysfunction in adipose tissue biology, characterized by an imbalance in adipocytokines secretion and alteration of their receptors within the tumor microenvironment. Many of these receptors belong to the seven-transmembrane receptor family, which are involved in physiological features, such as immune responses and metabolism, as well as in the development and progression of several malignancies, including breast cancer. These receptors are classified as canonical (G protein-coupled receptors, GPCRs) and atypical receptors, which fail to interact and activate G proteins. Among the atypical receptors, adiponectin receptors (AdipoRs) mediate the effect of adiponectin, the most abundant adipocytes-derived hormone, on breast cancer cell proliferation, whose serum levels are reduced in obesity. The adiponectin/AdipoRs axis is becoming increasingly important regarding its role in breast tumorigenesis and as a therapeutic target for breast cancer treatment. The objectives of this review are as follows: to point out the structural and functional differences between GPCRs and AdipoRs, and to focus on the effect of AdipoRs activation in the development and progression of obesity-dependent breast cancer.

Induction of periodontitis and oral microbiome dysbiosis in a mouse model with heart failure with preserved ejection fraction results in worsening hypertension and diastolic dysfunction

Abstract Introduction Heart Failure with Preserved Ejection Fraction (HFpEF) is characterized by increased inflammation and disruption of the nitric oxide (NO) pathway. Oral microbiota has an essential role in the generation of a large portion of the NO bioavailability pool in the human body. Periodontitis (PD) is a common inflammatory condition that contributes to the development of chronic low-grade inflammation, oral microbiota dysbiosis, and dysregulation of the NO hemostasis. Purpose In this study, we sought to investigate the direct effect of PD induction on HFpEF manifestation in a mouse model. Methods HFpEF was induced in 11-week-old C57/black male mice by high-fat diet and inhibition of NO synthase using L-NAME (Nω-nitro-l-arginine-methyl-ester) (a “2-hit-model”) for 10 weeks. PD was induced by oral infection with P. gingivalis. Diastolic function of the left ventricle (LV) was assessed by high-frequency echocardiography. Blood pressure (BP) was measured using CODA non-invasive tail-cuff system. Results Induction of PD resulted in a significantly impaired diastolic function demonstrated by more pronounced decrease in e' and increase in E/e' ratio compared to HFpEF without PD or control mice (E/e': 39.7±2.6 vs. 30.1±1.9 vs. 24.3±2.1 for PD-HFpEF [n=15], HFpEF [n=15], and controls [n=10], respectively, p<0.001). While LV ejection fraction (EF) was similar, global longitudinal strain (GLS) was decreased in the HFpEF group and further decreased in the PD-HFpEF group compared to controls (p<0.001). BP was elevated in the HFpEF mice and PD induction resulted in a more remarkable increase in BP (systolic BP: 124.7±3.3 vs. 112.7±3.8 vs. 94.8±2.2 mmHg, respectively, p<0.001). Conclusions Induction of PD in a mouse model with HFpEF results in a more pronounced BP elevation and diastolic dysfunction compared to HFpEF without PD. Extensive molecular experiments are ongoing to explore the mechanisms responsible for the increased HFpEF severity in the setting of PD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Israel Science Foundation

The link between cutaneous inflammation and cognitive impairment.

Cognitive impairment is a symptom of neurological disorders, including dementia and Alzheimer's disease; and mild cognitive impairment can be a precursor of both disorders. Aged humans and animal models with other systemic disorders, such as cardiovascular diseases and diabetes, display a higher incidence of cognitive decline. Epidemiological studies have shown that the incidence of cognitive impairment also is higher in subjects with certain inflammatory skin disorders, including psoriasis and chronic eczematous dermatitis. Chronologically aged individuals exhibit increased cutaneous inflammation and elevated circulating cytokine levels, linked to alterations in epidermal function, which itself can induce cutaneous inflammation. Conversely, strategies that improve epidermal function can lower cytokine levels in both the skin and circulation. Thus, it seems likely that epidermal dysfunction could contribute, at least in part, to the development of chronic low-grade inflammation, also termed 'inflammaging', in the elderly. The evidence of cognitive impairment in patients with inflammatory dermatoses suggests a link between cutaneous inflammation and cognitive impairment. Because of the pathogenic role of epidermal dysfunction in ageing-associated cutaneous inflammation, improvements in epidermal function could be an alternative approach for mitigation of the ageing-associated decline in cognitive function.

Obesity and functional bowel disorders in children

Obesity and functional bowel disorders (FBDs) are often observed in children and share common risk factors. However, the possible relationship between these conditions has begun to be studied recently and the results obtained are ambiguous. Therefore, it is important to summarize the literature on the relationship between obesity and FBDs in children and to discuss the possible pathophysiological mechanisms mediating this. The literature suggests that obesity and FBDs are likely associated conditions. A significant link between obesity and irritable bowel syndrome in children has been confirmed by all studies on this problem. There is also a many evidence that obesity in the pediatric cohort is associated with constipation. However, it should also be noted that there are few studies of this issue, they are heterogeneous in the composition of participants and the diagnostic criteria used, in most cases they are unadjusted for potential confounders. The link between obesity and FBDs may be mediated by diet, eating habits, and psychological factors. But the most promising direction in studying the association between these conditions may be studies of the gut microbiota, changes in which can contribute to impaired intestinal immune function, the development of chronic low-grade inflammation, increased intestinal permeability, impaired motility and visceral hypersensitivity. To date, there is insufficient data to confidently confirm the existence and nature of the relationship between obesity and FBDs in children, but research in this direction can provide important information for the development of approaches to treatment, prevention and early diagnosis of both groups of diseases.

Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly

With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Forty participants (70.3 ± 5.0 years) were randomly assigned to either a training (TG) or control group (CG) and performed a controlled low-threshold and care-oriented 6-week-long combined resistance and endurance training program. Changes in anthropometrics as well as strength capacity were measured. In subgroups of TG and CG, T cells and their subpopulations (CD4+, CD8+, naïve, central, effector memory, T-EMRA) were analyzed by flow cytometry. The changes of various plasma cytokines, chemokines, growth factors and adipokines were analyzed by luminex assays. The exercise program was followed by an increase in strength capacities. Participants of TG showed an increase of the CD4+/CD8+ T cell ratio over time (p < 0.05). Significant decreases in systemic levels of interleukin (IL-) 6, IL-8, IL-10 and vascular endothelial growth factor (VEGF) (p < 0.05) were observed for participants of TG over time. Even short-term and low-threshold training can reduce some of the hallmarks of immune aging in elderly and thus could be beneficial to stimulate immunity. The specific characteristics of the program make it easily accessible to older people, who may benefit in the longer term in terms of their immunocompetence.

TIR-Domain-Containing Adaptor-Inducing Interferon-β (TRIF) Is Involved in Glucose Metabolism in Adipose Tissue through the Insulin/AKT Signaling Pathway.

Obesity significantly increases the risk of developing type 2 diabetes mellitus and other metabolic diseases. Obesity is associated with chronic low-grade inflammation in white adipose tissues, which is thought to play an essential role in developing insulin resistance. Many lines of evidence indicate that toll-like receptors (TLRs) and their downstream signaling pathways are involved in development of chronic low-grade inflammation and insulin resistance, which are associated with obesity. Mice lacking molecules positively involved in the TLR signaling pathways are generally protected from high-fat diet-induced inflammation and insulin resistance. In this study, we have determined the effects of genetic deficiency of toll/interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (TRIF) on food intake, bodyweight, glucose metabolism, adipose tissue macrophage polarization, and insulin signaling in normal chow diet-fed mice to investigate the role of the TRIF-dependent TLR signaling in adipose tissue metabolism and inflammation. TRIF deficiency (TRIF−/−) increased food intake and bodyweight. The significant increase in bodyweight in TRIF−/− mice was discernible as early as 24 weeks of age and sustained thereafter. TRIF−/− mice showed impaired glucose tolerance in glucose tolerance tests, but their insulin tolerance tests were similar to those in TRIF+/+ mice. Although no difference was found in the epididymal adipose mass between the two groups, the percentage of CD206+ M2 macrophages in epididymal adipose tissue decreased in TRIF−/− mice compared with those in TRIF+/+ mice. Furthermore, activation of epididymal adipose AKT in response to insulin stimulation was remarkably diminished in TRIF−/− mice compared with TRIF+/+ mice. Our results indicate that the TRIF-dependent TLR signaling contributes to maintaining insulin/AKT signaling and M2 macrophages in epididymal adipose tissue under a normal chow diet and provide new evidence that TLR4-targeted therapies for type 2 diabetes require caution.

Elevated adipose tissue associated IL-2 expression in obesity correlates with metabolic inflammation and insulin resistance

Adipose tissue (AT) associated cytokines are involved in the development of chronic low-grade inflammation in obese individuals. IL-2, a pleiotropic cytokine, contributes to immune alterations during inflammation. However, the interaction between AT-IL-2 and other inflammatory biomolecules in obesity remains elusive. We investigated whether AT-IL-2 expression was associated with markers of inflammation and insulin resistance in overweight/obese individuals. Subcutaneous fat tissues were collected from 56 individuals (lean/overweight/obese) for RNA extraction. IL-2 and inflammatory mediators were quantified by qRT-PCR and immunohistochemistry. CRP was measured by ELISA. AT-IL-2 expression was higher in obese compared with lean individuals (P < 0.021) and correlated with BMI. IL-2 correlated with interleukins IL-8 and IL-12A (r = 0.333–0.481; p = 0.0001–0.029); as well as with chemokines and their receptors including CCL5, CCL19, CCR2 and CCR5 (r = 0.538–0.677; p < 0.0001). Moreover, IL-2 correlated with toll-like receptors (TLR2, TLR8, TLR10), interferon regulatory factor 5 (IRF5) and cluster of differentiation CD11c (r = 0.282–0.357; p < 0.039). Notably, IL-2 was associated positively with fasting blood glucose (FBG), HbA1c, TGL and CRP (r ≥ 0.423;P ≤ 0.007). In multiple regression analysis, IL-2 is an independent predictor of IL-8, IL-12A, TLR10, TGL and HbA1c. Overall, our data demonstrate that increased expression of the AT-IL-2, in obesity, may represent a novel biomarker for progression of metabolic inflammation and insulin-resistance.

PHYSICAL INACTIVITY, CHRONIC DISEASES, IMMUNITY AND COVID-19

ABSTRACT Complications arising from COVID-19 reflect an abnormal immune response in people previously diagnosed with chronic, non-communicable diseases (NCD), such as cardiovascular, metabolic and pulmonary conditions. Physical inactivity is recognized as a condition that affects the development of chronic low-grade inflammation, NCD, and susceptibility to cell infections. Anxiety and mental stress, poor nutritional status, drug use and circadian rhythm disturbances can further aggravate the harm caused by physical inactivity. Therefore, the purpose of the review is to invite health professionals, their respective regulatory boards, universities, research promotion foundations, media, political authorities and lay citizens to raise awareness of immunity and health in the medium- to long-term control of the current pandemic. Level of evidence V; Expert opinion.

Combined Black Rice Germ, Bran Supplement and Exercise Intervention Modulate Aging Biomarkers and Improve Physical Performance and Lower-Body Muscle Strength Parameters in Aging Population.

Aging is a time-dependent functional decline in muscle mass and strength, which is reflected in poor physical performances, hormonal imbalance, and development of chronic low-grade inflammation. This study aimed to assess the effectiveness of black rice germ, bran supplement, and exercise program either alone or in combination for 24 weeks on the aging biomarkers (C-reactive protein, Interleukin-6, Insulin-like growth factor-1, and CD4:CD8 T cell ratio) physical performance, muscle strength parameters (walking speed, sit-to-stand time, grip strength) among Thai aging population. A total of 120 healthy volunteers aged 65–74 years were assigned to the exercise group (EX), black rice germ, and bran supplement (BR) group or the combination of BR and EX group (BR + EX). Over the course of the 24-week intervention, compared with baseline data (T0), the combined BR + EX intervention significantly decreased the inflammatory biomarkers (C-reactive protein and interleukin-6 levels, both p < 0.05 vs. T0) and significantly increased the insulin-like growth factor-1 levels (p < 0.001 vs. T0). Significant improvement in physical performance and muscle strength were also observed in the combined BR + EX group (decrease in sit-to-stand time and gait speed over the 24-week intervention, both p < 0.05 vs. T0, and trend toward grip strength improvement at p = 0.088 vs. T0). Overall, our results indicated a synergistic effect towards the combined intervention with the sustainable improvement in physical performances, lower-body muscle strength, and the modulation of both inflammatory and endocrine biomarkers. This study could encourage older adults to change their lifestyles to improve healthy aging and longevity.

Baicalin Protects Against Hypertension-Associated Intestinal Barrier Impairment in Part Through Enhanced Microbial Production of Short-Chain Fatty Acids.

Impaired intestinal barrier plays an important role in the pathogenesis of hypertension primarily through promoting the development of chronic low-grade inflammation. Baicalin is the major flavonoid component of Scutellaria baicalensis Georgi, a medicinal plant commonly used for the treatment of inflammatory intestinal disorders and hypertension in traditional Chinese medicine. However, it remains to be elucidated whether baicalin alleviates hypertension-associated intestinal barrier impairment. The current study thus investigated the effects of baicalin on the intestinal barrier integrity, the intestinal expression of genes encoding proinflammatory factors and tight junction proteins, the serum levels of the inflammatory markers, the amount of fecal short-chain fatty acids (SCFAs) and the abundance of SCFAs-producing bacteria in the spontaneously hypertensive rats (SHRs). The results showed that baicalin alleviated the pathological lesions in the ilium and the proximal colon in the SHRs. Baicalin treatment resulted in decreased ileal and colonic expression of proinflammatory genes in the SHRs. In addition, baicalin treatment attenuated hypertension-associated intestinal hyperpermeability and decreased the serum levels of inflammatory indicators such as high-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta, and IL-6 in the SHRs. The protective effect of baicalin on the intestinal integrity was also supported by well-preserved intestinal ultrastructure and increased intestinal expression of genes encoding tight junction proteins such as zonula occludens-1 (ZO-1), cingulin, and occludin in the SHRs. Lastly, baicalin treatment increased the amount of fecal SCFAs and the abundance of SCFAs-producing bacteria in the SHRs. In conclusion, the work here provides for the first time the morphological, biochemical, and molecular evidence supporting the protective effects of baicalin on the intestinal integrity in the SHRs, which may help better understand the therapeutic effects of S. baicalensis Georgi in the treatment of hypertension.

Adipose tissue expression of CCL19 chemokine is positively associated with insulin resistance.

BackgroundChemokines produced by adipose tissue (AT) are involved in the development of chronic low‐grade inflammation in obese humans and rodents. AT CCL19 expression in obesity and its association with metabolic inflammation and insulin resistance are poorly understood. This study aimed to investigate the effects of CCL19 gene expression on inflammatory markers in subcutaneous AT and insulin resistance.MethodsSubcutaneous adipose samples were collected from 56 non‐diabetic (26—obese, 21—overweight, and 9—lean) individuals. Expression of CCL19 and inflammatory markers was determined using real‐time RT‐PCR. Plasma C‐reactive protein (CRP) and adiponectin were measured by ELISA. Insulin sensitivity was assessed using homeostasis model assessment index (HOMA).ResultsCCL19 expression was significantly higher in obese compared with lean individuals (P < 0.034). The elevated expression of CCL19 associated positively with body mass index (r = 0.253; P = 0.049). CCL19 expression correlated positively with IL‐8 (r = 0.39; P = 0.006), IL‐12 (r = 0.43; P = 0.003), IP‐10 (r = 0.25; P = 0.07), CCL5 (r = 0.37; P = 0.011), CCR2 (r = 0.44; P = 0.001), and CCR5 (r = 0.35; P = 0.009). Additionally, CCL19 was positively correlated with triglycerides (TG: r = 0.41; P = 0.001), fasting blood glucose (FBG: r = 0.49; P < 0.0001), glycated haemoglobin (HbA1c: r = 0.396; P = 0.001), and CRP (r = 0.387; P = 0.019) whereas it had negative association with HDL cholesterol (r = −0.282; P = 0.035) and adiponectin (−0.393; P = 0.019). Notably, HOMA‐IR correlated positively with CCL19 (r = 0.38; P = 0.01). In multiple regression analysis, CCL19 is an independent predictor of IL‐8 and IL‐12.ConclusionsThese data demonstrate that increased AT expression of CCL19 in obesity may represent a molecular link between metabolic inflammation and insulin resistance.

Elevated adipose tissue expression of CCL19 in obese individuals with or without type-2 diabetes: Its association with metabolic inflammation

Abstract Adipose tissue produces inflammatory molecules considered to be involved in the development of chronic low-grade inflammation in obesity and type 2 diabetes (T2D). The adipose tissue expression of CCL19 or macrophage inflammatory protein (MIP)-3β in obesity is poorly understood. We, therefore, determined CCL19 gene expression in the adipose tissue samples from lean, overweight, and obese individuals with or without T2D. Subcutaneous adipose samples were collected from 58 non-diabetic (ND) (27-obese, 21-overweight, and 10-lean) and 49 T2D (34-obese, 11-overweight, and 4-lean) individuals. Gene expression of CCL19 and other inflammatory markers was determined using real-time RT-PCR. Plasma CRP and adiponectin were measured by ELISA. CCL19 expression was significantly higher in obese compared with lean individuals (ND: P&amp;lt;0.04; T2D: P&amp;lt;0.02). Notably, CCL19 expression was relatively higher in T2D than ND individuals regarding each body mass index (BMI) group. CCL19 expression correlated with BMI (ND: r=026, p=0.04; T2D: r=0.45, P=0.001). In relation to immune markers, CCL19 expression had association with CXCL10, IL-12A, and TLR2 in ND individuals, and with IL-6, IL-1β, TGF-β, TNF-α, TLR9, CCL11 and IRAK-1 in T2D individuals, while it associated with MyD88, CCL5, CCR2, and CRP in both populations. However, CCL19 gene expression associated negatively with adiponectin in ND individuals. With regard to clinical markers, in both populations, CCL19 expression correlated positively with triglycerides, fasting blood glucose, and HbA1C, whereas it had negative association with HDL cholesterol. These data support that increased adipose tissue expression of CCL19 may represent an immune signature of metabolic inflammation.

Mast cells participate in chronic low-grade inflammation within adipose tissue.

Obesity is reckoned as one of the civilization diseases, posing a considerable global health issue. Evidence points towards a contribution of multitude immune cell populations in obesity pathomechanism and the development of chronic low-grade inflammation in the expanded adipose tissue. Notably, adipose tissue is a reservoir of mast cells which number in individuals with obesity particularly increased. Some of them tend to degranulation what generate secretion of strong pro-inflammatory and regulatory mediators, as well as cytokines/chemokines. Several lines of evidence suggest that mast cells are strictly associated with pro-inflammatory status in adipose tissue by their indirect impact on immune cell attraction and activation. Furthermore, mast cells affect adipose tissue remodelling and fibrosis by adipocyte differentiation, fibroblast proliferation and enhancing extracellular matrix proteins expression. This review will summarize current knowledge on mast cell features and their role in the development of chronic low-grade inflammation within adipose tissue.

Lymphocytes and macrophages in adipose tissue in obesity: markers or makers of subclinical inflammation?

Obesity is accompanied by the development of chronic low-grade inflammation in adipose tissue. The presence of chronic inflammatory response along with metabolically harmful factors released by adipose tissue into the circulation is associated with several metabolic complications of obesity such as type 2 diabetes mellitus or accelerated atherosclerosis. The present review is focused on macrophages and lymphocytes and their possible role in low-grade inflammation in fat. Both macrophages and lymphocytes respond to obesity-induced adipocyte hypertrophy by their migration into adipose tissue. After activation and differentiation, they contribute to the development of local inflammatory response and modulation of endocrine function of adipose tissue. Despite intensive research, the exact role of lymphocytes and macrophages within adipose tissue is only partially clarified and various data obtained by different approaches bring ambiguous information with respect to their polarization and cytokine production. Compared to immunocompetent cells, the role of adipocytes in the obesity-related adipose tissue inflammation is often underestimated despite their abundant production of factors with immunomodulatory actions such as cytokines or adipokines such as leptin, adiponektin, and others. In summary, conflicting evidence together with only partial correlation of in vitro findings with true in vivo situation due to great heterogeneity and molecular complexity of tissue environment calls for intensive research in this rapidly evolving and important area.

Exploring the molecular basis of age-related disease comorbidities using a multi-omics graphical model.

Although association studies have unveiled numerous correlations of biochemical markers with age and age-related diseases, we still lack an understanding of their mutual dependencies. To find molecular pathways that underlie age-related diseases as well as their comorbidities, we integrated aging markers from four different high-throughput omics datasets, namely epigenomics, transcriptomics, glycomics and metabolomics, with a comprehensive set of disease phenotypes from 510 participants of the TwinsUK cohort. We used graphical random forests to assess conditional dependencies between omics markers and phenotypes while eliminating mediated associations. Applying this novel approach for multi-omics data integration yields a model consisting of seven modules that represent distinct aspects of aging. These modules are connected by hubs that potentially trigger comorbidities of age-related diseases. As an example, we identified urate as one of these key players mediating the comorbidity of renal disease with body composition and obesity. Body composition variables are in turn associated with inflammatory IgG markers, mediated by the expression of the hormone oxytocin. Thus, oxytocin potentially contributes to the development of chronic low-grade inflammation, which often accompanies obesity. Our multi-omics graphical model demonstrates the interconnectivity of age-related diseases and highlights molecular markers of the aging process that might drive disease comorbidities.

Clinical and metabolic factors associated with chronic low-grade inflammation in type 2 diabetic patients

Aim. To identify the clinical and metabolic factors associated with serum concentration of high sensitivity C-reactive protein (hsCRP) and α1-acid glycoprotein (α1-AGP) in patients with type 2 diabetes.Material and methods. The study involved 210 patients with type 2 diabetes. Levels of hsCRP and α1-AGP were measured using ELISA and compared with those of the control (30 healthy normal individuals). Levels of acute-phase proteins, fat mass and glucose variability (GV) were compared among demographic, anthropometric, biochemical and haematological parameters. The fat mass was determined with Dual-energy X-ray absorptiometry (DEXA). GV parameters including mean amplitude of glycaemic excursions, continuous overlapping net glycaemic action (CONGA), J-index, M-value and mean absolute glucose change (MAG) were derived from continuous glucose monitoring.Results. Levels of hsCRP and α1-AGP significantly increased (p 0.0001) in patients with diabetes compared with controls. hsCRP level positively correlated with total, truncal and android fat (r = 0.34, r = 0.28 and r = 0.31; respectively, p 0.00004). α1-AGP level showed no relationship with fat mass but positively correlated with mean glucose, CONGA, M-value and MAG (r = 0.38, r = 0.36, r = 0.43 and r = 0.4; respectively, p 0.0001). Patients with the highest hsCRP levels (75 percentile) had a greater body mass index (p = 0.00009) as well as truncal and android fat mass (p = 0.04 and p = 0.03, respectively) than those with the lowest levels (25 percentile). High level of α1-AGP (75 percentile) was associated with urinary albumin/creatinine ratio (p = 0.01) and GV indices (M-value: p = 0.02, MAG: p = 0.04).Conclusions. Levels of acute-phase proteins (hsCRP and α1-AGP) increased in patients with type 2 diabetes. Levels of hsCRP were associated with fat mass; meanwhile, α1-AGP levels were associated with short-time GV in these patients. The results lend support to the notion that both obesity and enhanced GV are involved in the development of chronic low-grade inflammation associated with type 2 diabetes.

The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation

Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity.