Chronic Low-level Inflammation Research Articles

Mechanisms of Calorie Restriction: A Review of Genes Required for the Life-Extending and Tumor-Inhibiting Effects of Calorie Restriction

This review focuses on mechanisms of calorie restriction (CR), particularly the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis as an evolutionary conserved signal that regulates aging and lifespan, underlying the effects of CR in mammals. Topics include (1) the relation of the GH-IGF-1 signal with chronic low-level inflammation as one of the possible causative factors of aging, that is, inflammaging, (2) the isoform specificity of the forkhead box protein O (FoxO) transcription factors in CR-mediated regulation of cancer and lifespan, (3) the role for FoxO1 in the tumor-inhibiting effect of CR, (4) pleiotropic roles for FoxO1 in the regulation of disorders, and (5) sirtuin (Sirt) as a molecule upstream of FoxO. From the evolutionary view, the necessity of neuropeptide Y (Npy) for the effects of CR and the pleiotropic roles for Npy in life stages are also emphasized. Genes for mediating the effects of CR and regulating aging are context-dependent, particularly depending on nutritional states.

Tendon healing in presence of chronic low-level inflammation: a systematic review.

Tendinopathy is a common musculoskeletal condition affecting subjects regardless of their activity level. Multiple inflammatory molecules found in ex vivo samples of human tendons are related to the initiation or progression of tendinopathy. Their role in tendon healing is the subject of this review. An extensive review of current literature was conducted using PubMed, Embase and Cochrane Library using the term 'tendon', as well as some common terms of tendon conditions such as 'tendon injury OR (tendon damage) OR tendonitis OR tendinopathy OR (chronic tendonitis) OR tendinosis OR (chronic tendinopathy) OR enthesitis' AND 'healing' AND '(inflammation OR immune response)' as either key words or MeSH terms. An environment characterized by a low level of chronic inflammation, together with increased expression of inflammatory cytokines and growth factors, may influence the physiological tendon healing response after treatment. Most studies on this topic exhibited limited scientific translational value because of their heterogeneity. The evidence associated with preclinical studies is limited. The role of inflammation in tendon healing is still unclear, though it seems to affect the overall outcome. A thorough understanding of the biochemical mediators of healing and their pathway of pain could be used to target tendinopathy and possibly guide its management. We require further studies with improved designs to effectively evaluate the pathogenesis and progression of tendinopathy to identify cellular and molecular targets to improve outcomes.

Effect of Systemic Inflammation on Rat Attentional Function and Neuroinflammation: Possible Protective Role for Food Restriction.

Background: Aging is characterized by subtle cognitive decline, which correlates with increased peripheral inflammation. Acute activation of the peripheral immune system, via lipopolysaccharide (LPS) injection, elicits deficits in hippocampal-dependent spatial memory. Little is known concerning the effect of chronic inflammation on prefrontal cortex (PFC)-dependent vigilance. We examined the impact of repeated LPS injections in young and middle-age rats on the 5-choice serial reaction time task (5-CSRTT), expecting repeated LPS treatment to induce attentional deficits with greater disruption in middle-age.Methods: Male Fischer-344 rats, 4- and 12-months-old, were food restricted and trained on the 5-CSRTT. Once rats reached criterion, they were injected with LPS (1 mg/kg, i.p.) weekly for 4 weeks and testing started 48 h after each injection. To examine the possibility that mild food restriction inherent to the behavioral task influenced inflammation markers, a second group of food-restricted or ad-lib-fed rats was assessed for cytokine changes 48 h after one injection.Results: Performing LPS-treated rats exhibited a sickness response, manifesting as reduced initiated and completed trials during the first week but recovered by the second week of testing. After the first week, LPS-treated rats continued to exhibit longer response latencies, despite no change in food retrieval latency, suggestive of LPS-induced cognitive slowing. Similarly, LPS-induced impairment of attention was observed as increased omissions with heightened cognitive demand and increased age. Repeated LPS-treatment increased the level of PFC IL-1α, and PFC IL-6 was marginally higher in middle-age rats. No effect of age or treatment was observed for plasma cytokines in performing rats. Histological examination of microglia indicated increased colocalization of Iba1+ and CD68+ cells from middle-age relative to young rats. Examination of food restriction demonstrated an attenuation of age- and LPS-related increases in plasma cytokine levels.Conclusions: Systemic inflammation, induced through LPS treatment, impaired attentional function, which was independent of sickness and exacerbated by increased cognitive demand and increased age. Additional studies revealed that food restriction, associated with the task, attenuated markers of neuroinflammation and plasma cytokines. The results emphasize the need for improved methods for modeling low-level chronic systemic inflammation to effectively examine its impact on attention during aging.

Urinary Biomarkers of Inflammation and Oxidative Stress Are Elevated in Obese Children and Correlate with a Marker of Endothelial Dysfunction.

Obesity is a state of chronic low-level inflammation closely associated with oxidative stress. Childhood obesity is associated with endothelial dysfunction, inflammation, and oxidative stress markers individually. This study was aimed at determining the association between the biomarkers of inflammation, oxidative stress, and endothelial dysfunction in urine samples of healthy, overweight, and obese children. Eighty-eight elementary school children aged between 6 and 10 years participated in this study. Anthropometric measurements were measured using WHO recommendations. The biomarkers of low-grade inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), and α-1-acid glycoprotein (AGP); oxidative stress markers such as 8-isoprostane and 8-hydroxy-2′-deoxyguanosine (8-OHdG); and endothelin-1 (ET-1) were analyzed in urine samples. The area under the curve (AUC) by the receiver operating characteristics (ROC) was analyzed to identify the best urinary biomarker in childhood obesity. Linear regression and Pearson correlation were analyzed to determine the association between the parameters. The obese participants have significantly increased levels of CRP, AGP, IL-6, and 8-isoprostane compared to normal-weight participants. The overweight participants had significantly increased levels of ET-1 and 8-OHdG but not the obese group compared to the NW group. The AUC for urinary CRP (AUC: 0.847, 95% CI: 0.765-0.930; p < 0.0001) and 8-isoprostane (AUC: 0.857, 95% CI: 0.783-0.932; p < 0.0001) showed a greater area under ROC curves compared to other inflammatory and oxidative markers. The urinary CRP and 8-isoprostane significantly correlated with the obesity measures (body mass index, waist circumference, and waist-to- height ratio) and ET-1, inflammatory, and oxidative markers. The increased urinary inflammatory markers and 8-isoprostane can serve as a noninvasive benchmark for early detection of the risk of developing cardiovascular disease.

The Association Between Inflammaging and Age-Related Changes in the Ruminal and Fecal Microbiota Among Lactating Holstein Cows.

Inflammaging is well understood in the study of humans; however, it is rarely reported for dairy cows. To understand the changing pattern of the gut microbiota, inflammatory status and milk production performance during the aging process in cows, we grouped 180 cows according to their lactation period: L1 (n = 60, 1st lactation), L3 (n = 60, 3rd lactation), and L5+ (n = 60, at least 5th lactation) and analyzed their milk components and daily milk yields to evaluate the changing pattern of milk production. The microbiota was analyzed using high-throughput sequencing of amplicons of 16S rRNA, which also allowed us to predict the functions of microbes and then study the changing pattern of the ruminal and fecal microbiota. Serum cytokines, including TNF-α, IL-6, IL-10, and TGF-β were measured to study the progress of inflammaging in the cows. We found that old cows (L5+) suffered from a long-term and low-level chronic inflammation, as indicated by significantly higher levels of inflammatory cytokines IL-10, TNF-α, and TGF-β in the L5+ group (p < 0.001). We also observed a significant decrease in daily milk yield and milk lactose, as well as a significant increase in somatic cell score, among the cows in the L5+ group. For the gut microbiota, most of the genera belonging to Prevotellaceae and Lachnospiraceae, which had a higher abundance among cows of both the L1 and L3 groups (LEfSe, LDA > 2), showed a similar change pattern during the aging process, both in the rumen and in feces, and across the six farms. Beneficial bacteria, like Bacteroidaceae, Eubacterium, and Bifidobacterium, displayed lower abundance in the feces of the L5+ group (LEfSe, LDA > 2). Reconstruction of the fecal bacteria community indicated transformation of the fermenting pattern of older cows’ (L5+) feces microbiota, with increased functions related the protein metabolism and fewer functions related to carbohydrate and lipid metabolism compared with those in L1 (p < 0.05). Finally, the connections among these changing patterns were revealed using redundancy analysis and network analysis. The results support the hypothesis of prolonging a cows’ productive life and improve dairy cow milk productive performances by manipulating the gut microbiota.

2054-P: Endothelial Dysfunction, Inflammation, and Oxidative Stress Urinary Biomarkers in Obese Children from Alabama

Obesity is a state of chronic low-level inflammation closely associated with the oxidative stress. Childhood obesity has been related to endothelial dysfunction, inflammation and oxidative stress markers individually. The aim of this study was to determine the association of biomarkers of the inflammation, oxidative stress and endothelial dysfunction in urine samples of healthy and obese children. Thirty healthy and thirty overweight/obese elementary school children aged between 6 to 10 years from Alabama participated in this study. Anthropometric measurements were measured using WHO recommendations. Urine samples were analyzed for biomarkers of low-grade inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP), α-1-acid glycoprotein (AGP); oxidative stress such as 8-isoprostane, 8-hydroxy-2'-deoxyguanosine (8-OHdG); and endothelin-1 (ET-1). Linear regression analysis was performed to analyze the association between the parameters. The overweight/obese children have significantly increased levels of IL-6, CRP, ET1 and 8-isoprostane compared to normal weight. CRP, IL-6, AGP and 8-isoprostane have significant positive association with at least one of the obesity measures except the ET-1 and 8-OHdG. ET-1 is significantly positively correlated with IL-6 and 8-isoprostane. The increased urinary IL-6 and 8-isoprostane can be used as a non-invasive benchmark to monitor childhood obesity. Disclosure V. Selvaraju: None. P. Ayine: None. E.P. Parra: None. M. Brown: None. R.B. Jeganathan: None. G. Thangiah: None. Funding National Institute of Food and Agriculture

Is Chickpea a Potential Substitute for Soybean? Phenolic Bioactives and Potential Health Benefits.

Legume seeds are rich sources of protein, fiber, and minerals. In addition, their phenolic compounds as secondary metabolites render health benefits beyond basic nutrition. Lowering apolipoprotein B secretion from HepG2 cells and decreasing the level of low-density lipoprotein (LDL)-cholesterol oxidation are mechanisms related to the prevention of cardiovascular diseases (CVD). Likewise, low-level chronic inflammation and related disorders of the immune system are clinical predictors of cardiovascular pathology. Furthermore, DNA-damage signaling and repair are crucial pathways to the etiology of human cancers. Along CVD and cancer, the prevalence of obesity and diabetes is constantly increasing. Screening the ability of polyphenols in inactivating digestive enzymes is a good option in pre-clinical studies. In addition, in vivo studies support the role of polyphenols in the prevention and/or management of diabetes and obesity. Soybean, a well-recognized source of phenolic isoflavones, exerts health benefits by decreasing oxidative stress and inflammation related to the above-mentioned chronic ailments. Similar to soybeans, chickpeas are good sources of nutrients and phenolic compounds, especially isoflavones. This review summarizes the potential of chickpea as a substitute for soybean in terms of health beneficial outcomes. Therefore, this contribution may guide the industry in manufacturing functional foods and/or ingredients by using an undervalued feedstock.

An act of balance: Interaction of central and peripheral chemosensitivity with inflammatory and anti-inflammatory factors in obstructive sleep apnoea

ObjectivesCentral and peripheral chemosensitivity i.e. ventilatory response to CO2 and O2 are thought to be decisive for ventilatory control instability in obstructive sleep apnoea (OSA). Obesity is associated with chronic low level inflammation. Whether body mass related inflammatory and anti-inflammatory factors influencing peripheral and central chemosensitivity differentially is unclear. MethodsVentilatory response to hypercapnic-hyperoxic and hypercapnic-hypoxic gas mixtures in patients with OSA (n = 46) and healthy individuals (n = 45) was measured. C-reactive protein (CRP), leptin, adiponectin, and endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) were measured in blood samples. ResultsMediation analysis revealed that association of chemoresponse to CO2 with apnoea hypopnea index (AHI) was fully mediated by body mass index (BMI). Regression analysis showed that CRP and leptin levels explained ˜25% and ˜15% of the variance in central CO2 response, while 2-AG explained ˜42% of the variance in peripheral response to hypoxia. ConclusionInflammatory and anti-inflammatory factors could explain differential alterations in peripheral and central ventilatory chemoresponse in patients with OSA.

Advanced Glycation End Products As Biomarkers in Systemic Diseases: Premises and Perspectives of Salivary Advanced Glycation End Products

Advanced glycation end products (AGEs) are glycated proteins associated with high dry temperature food processing, coloring and flavor modification of food products. Previous studies on diet-related disease support the role of the glycation products as biomarkers in local and general proinflammatory response. Exogenous and endogenous AGEs are involved in chronic low-level inflammation, which underlies the onset of metabolic syndrome influenced by food intake, there by demonstrating their implication in diet-related pathologies. Although studies have revealed a strong association between the accumulation of AGEs and the occurrence/worsening of metabolic diseases, their routine use for the diagnosis or monitoring of local and general disease has not yet been reported.

T-cell immunity against cytomegalovirus in HIV infection and aging: relationships with inflammation, immune activation, and frailty.

Both aging and treated human immunodeficiency virus (HIV) infection are characterized by low-level chronic inflammation and immune activation which contribute to the development of age-related diseases, frailty, and early mortality. Chronic cytomegalovirus (CMV) infection is highly prevalent in older adults and HIV-infected populations. A number of studies have shown that CMV induces broad and strong T-cell responses in CMV-seropositive older adults and HIV-infected individuals. CMV infection rarely develops into clinical disease in immunocompetent individuals. However, a large body of literature has shown adverse effects of chronic CMV infection on the health and longevity of these populations. It has been hypothesized that chronic CMV infection may be a driver of chronic inflammation and immune activation, and may further contribute to the development of frailty. Thus, there is a need to better understand the extent of the impact of chronic CMV infection on T-cell immunity and health in aging and HIV infection. In this review, we will address important considerations and challenges in the assessment of chronic CMV infection and CMV-specific T-cell responses. We will then review recent data on relationships between T-cell responses to CMV and levels of inflammatory markers and immune activation, as well as the onset of frailty.

Inflammation the Kingpin of Chronic Diseases Naturopathy as an alternative source of treatment: An updated overview

Inflammation involves a sequence of events which can be categorized under three phases viz. acute transient phase, delayed sub-acute phase and chronic proliferate phase. Inflammatory mediators develop due to enhanced vascular permeability and leads to local edema. It is followed by the migration of leukocytes and phagocytes from blood to vascular tissues which is the second phase, in the third phase, tissue degradation is followed by fibrosis. There is a powerful link between chronic diseases and chronic inflammatory disorders. Chronic low-level inflammation contributes to the pathogenesis of these several diseases like Heart disease, Cancer, Chronic lower respiratory disease, Stroke, Alzheimer’s, Diabetes, and Nephritis. The harmful side effects of synthetic drugs are numerous and there stands up the need of herbal drugs which are cost effective and free from side-effects. Several traditional ayurvedic phytomedicines have been used in the treatment of inflammatory disorders like Ocimum sanctum, Hypericum peroratum, Boswellic serrata, Ficus racemosa etc. which act as natural anti-inflammatory agents that can help in reducing the complications associated with chronic diseases.&#x0D; Key Words: Inflammation, Chronic-low level inflammation, Cancer, Diabetes, Phytomedicines

Serum Calcium Concentrations, Chronic Inflammation and Glucose Metabolism: A Cross-Sectional Analysis in the Andhra Pradesh Children and Parents Study (APCaPS)

BackgroundEvidence suggests a role for elevated serum calcium in dysregulated glucose metabolism, linked through low-level chronic inflammation. ObjectivesWe investigated the association of elevated serum calcium concentrations (corrected for albumin) with markers of dysregulated glucose metabolism and type II diabetes and tested if these associations were accounted for by chronic inflammation in a rural Indian population. MethodsA cross-sectional analysis of participants aged 40–84 y from the Andhra Pradesh Children and Parents Study (APCaPS; n = 2699, 52.2% women) was conducted. Comprehensive information on household, sociodemographic, and lifestyle factors; medical and family history; physical measurements; blood measurements including fasting plasma glucose (FPG), fasting insulin (FI), serum calcium, albumin, phosphorous, vitamin D (in a subset), and creatinine were analyzed. Additionally, in a random sample of healthy participants (n = 1000), inflammatory biomarkers (interleukins 6 and 18, soluble intercellular adhesion molecule 1, adiponectin, and high-sensitivity C-reactive protein) were measured and an inflammatory score (IScore) calculated. ResultsAfter adjustments for sociodemographics, lifestyle factors, and anthropometry the highest calcium quartile (Q4 compared with Q1) was associated with FI (β = 1.4 µU/ml; 95% CI: 1.2, 1.5 µU/ml; P-trend < 0.001), the homeostasis model assessment for insulin resistance (HOMA-IR) (β = 1.4; 95% CI: 1.2, 1.5; P-trend < 0.001), and was modestly associated with FPG (β = 2.1 mg/dL; 95% CI: −0.9, 5.2 mg/dL; P-trend = 0.058) and prevalent type II diabetes (OR = 1.6; 95% CI: 1.0, 2.6; P-trend= 0.020). In the healthy subgroup, the association of the highest calcium quartile was similar for FI and HOMA-IR. Additional adjustment with IScore did not alter the associations. Further, in a subset, all these associations were independent of endogenous regulators of calcium metabolism (serum vitamin D, phosphorus, and creatinine). Independently, after accounting for potential confounders, the highest IScore quartile (Q4 compared with Q1) was positively associated with FPG, FI, HOMA-IR, and prevalent prediabetes, and also with serum calcium concentrations in men. ConclusionsElevated serum calcium was positively associated with markers of dysregulated glucose metabolism and prevalent type II diabetes in a rural Indian population. Chronic inflammation did not mediate this association but was independently associated with markers of dysregulated glucose metabolism. Inflammation might be responsible for elevated serum calcium concentrations in men.

SARCOPENIA, SARCOPENIC OBESITY AND FRAILTY; LINKS TO COGNITIVE PERFORMANCE IN ELDERS: Session 412

Background: According to 2011 CDC data, more than 2.6 million adults aged 60 and older with cognitive impairment reported difficulty performing one or more ADLs. There are studies that link cognitive decline and physical impairment in terms of low-level chronic inflammation, oxidative stress, and depression. Skeletal muscle can produce IL-1, IL-6 and other important myokines that have been implicated in cognitive and physical functional degenerative processes. Oxidative stressors have been linked to physical frailty and sarcopenia as well as neurodegenerative processes further worsening cognitive impairment. What are Sarcopenia and Sarcopenic Obesity and its impacts on elders? Sarcopenia is a primary disease of the elderly population, characterized by loss of skeletal muscle mass and function. Sarcopenia is correlated with physical disability, poor quality of life, frailty, cognitive impairment, and death. Age, gender, and level of physical activity are the risk factors for the Sarcopenia. In addition to aging, malignancy and rheumatoid arthritis causes loss of lean body mass and even increase in body fat mass. The loss of muscle mass associated with increased body fat mass i.e. sarcopenic obesity causes weakness in aging. Sarcopenia, with or without obesity, results in impairment of IADL (Instrumental Activity of Daily Living) and eventually ADLs (Activities of Daily Living) among elders and results in need for long-term care and increased cost of health care. What is the link between Sarcopenia and Cognitive Impairment? Sarcopenia has not only has a greater effect on survival but also on cognitive impairment. Sarcopenia has been linked to global cognitive impairment and dysfunction in specific cognitive skills including memory, speed, and executive functions. While obesity may impair the executive functions of aging, the exact mechanism linking obesity to cognitive dysfunction is not clear. Improvement in muscular function of obese older adults has been linked to improvement of executive functions. Obesity and Sarcopenia were associated with the lower executive function such as working memory, mental flexibility, self-control and orientation when assessed independently and even more so when they occurred together. Sarcopenia is highly correlated with frailty and risk of falls in elders; it also represents an important risk factor for disability and mortality. Frailty is an independent predictor of dementia. How do you assess for the Sarcopenia? Sarcopenia with or without obesity can be used in clinical practice to assess the potential risk of cognitive impairment in elders. There are several ways to measure Sarcopenia – DEXA (Dual-Energy X-ray Absorptiometry), biometric impedance analysis (BIA), CT (Computed Tomography) scan and MRI (Magnetic Resonance Imaging). However, assessing BMI and testing grip strength by dynamometry can be easily administered during annual wellness visits to assess the risk of sarcopenic related cognitive impairments. Sarcopenia can be assessed using parameters such as 1) Measure walking speed in elderly (>65 years). If the walking speed is below 0.8 m/s at the 4-m walking test, measure the muscle mass. 2) Hand- grip strength if this value is lower than 20kg in women and 30kg in man then muscle mass must be analyzed. 3) Defining Fat mass and lean body mass using BIA 4) Muscle Mass assessment by DEXA or CT. What is the significance of assessing the Sarcopenia? It is important to identify the risk of cognitive impairment by assessing for the onset of this condition. Preventing or delaying onset will likely enhance survival and reduce the demand for long-term care. Increasing resistance physical training will help to improve physical deconditioning, strengthen skeletal muscle hypertrophy, overcome the pain syndrome and enhance overall mental well-being. Interventions such as resistance exercise and nutritional therapy need to be developed specifically to delay the onset of Sarcopenia. What is the need in the future? Team-based approach including multidisciplinary model involving primary care physicians, geriatric psychiatrists, pain management physicians and physical therapists is required to combat the complex interlinked Sarcopenia associated cognitive impairment. Screening programs that include identification of cognitive and functional impairment in the office setting will serve as the starting point for specific interventions. The training regimen that includes supervision and correct equipment with resistance exercise will be necessary to get proper training and delay the muscle loss in elderly.

Modeling the Effect of High Calorie Diet on the Interplay between Adipose Tissue, Inflammation, and Diabetes.

Background Type 2 diabetes (T2D) is a chronic metabolic disease potentially leading to serious widespread tissue damage. Human organism develops T2D when the glucose-insulin control is broken for reasons that are not fully understood but have been demonstrated to be linked to the emergence of a chronic inflammation. Indeed such low-level chronic inflammation affects the pancreatic production of insulin and triggers the development of insulin resistance, eventually leading to an impaired control of the blood glucose concentration. On the contrary, it is well-known that obesity and inflammation are strongly correlated. Aim In this study, we investigate in silico the effect of overfeeding on the adipose tissue and the consequent set up of an inflammatory state. We model the emergence of the inflammation as the result of adipose mass increase which, in turn, is a direct consequence of a prolonged excess of high calorie intake. Results The model reproduces the fat accumulation due to excessive caloric intake observed in two clinical studies. Moreover, while showing consistent weight gains over long periods of time, it reveals a drift of the macrophage population toward the proinflammatory phenotype, thus confirming its association with fatness.

CCL22 is a biomarker of cartilage injury and plays a functional role in chondrocyte apoptosis

BackgroundOsteoarthritis (OA) is one of the leading causes of disability worldwide. Previous history of knee injury is a significant risk factor for OA. It has been established that low-level chronic inflammation plays a pivotal role in the onset and pathogenesis of OA. The primary aim of this research was to determine if a history of knee joint injury is associated with systemic inflammation. A secondary aim was to determine if systemic inflammation is related to knee pain and joint structure. MethodsDifferences in serum cytokine association networks, knee joint structural changes (MRI), and self-reported pain (i.e., Knee Injury and Osteoarthritis Outcome Score Pain subscale, KOOSPAIN and Intermittent and Constant Osteoarthritis Pain score, ICOAP) between individuals who had sustained a youth (aged 15–26 years) sport-related knee injury 3–10 years previously and age- and sex-matched controls were examined. Proteins of interest were also examined in an OA rat model. ResultsCytokine association networks were found to differ significantly between study groups, yet no significant associations were found between networks and KOOSPAIN or MRI-defined OA. A group of cytokines (MCP1/CCL2, CCL22 and TNFα) were differentially associated with other cytokines between study groups. In a pre-clinical rat OA model, serum CCL22 levels were associated with pain (r = 0.255, p = 0.045) and structural changes to the cartilage. CCL22 expression was also observed in human OA cartilage and furthermore, CCL22 induced apoptosis of isolated human chondrocytes. DiscussionThese results suggest that CCL22 may be an early factor in the onset/pathogenic process of cartilage degeneration and/or related to pain OA.

Cytometric analysis of adipose tissue reveals increments of adipocyte progenitor cells after weight loss induced by bariatric surgery

Obesity-related comorbidities are, in large part, originated from the dysfunction of adipose tissue. Most of them revert after the normalization of body mass. Adipose tissue is essentially occupied by adipocytes. However, different populations of immunological cells and adipocyte precursor cells (AdPCs) are the main cellular components of tissue. During obesity, body fat depots acquire a low-level chronic inflammation and adipocytes increase in number and volume. Conversely, weight loss improves the inflammatory phenotype of adipose tissue immune cells and reduces the volume of adipocytes. Nevertheless, very little is known about the evolution of the human AdPCs reservoir. We have developed a flow cytometry-based methodology to simultaneously quantify the main cell populations of adipose tissue. Starting from this technical approach, we have studied human adipose tissue samples (visceral and subcutaneous) obtained at two different physiological situations: at morbid obesity and after bariatric surgery-induced weight loss. We report a considerable increase of the AdPCs reservoir after losing weight and several changes in the immune cells populations of adipose tissue (mast cells increase, neutrophils decrease and macrophages switch phenotype). No changes were observed for T-lymphocytes, which are discussed in the context of recent findings.

Exploring the associations between systemic inflammation, obesity and healthy days: a health related quality of life (HRQOL) analysis of NHANES 2005\u20132008

BackgroundObesity is positively associated with low-level chronic inflammation, and negatively associated with several indices of health-related quality of life (HRQOL). It is however not clear if obesity-associated inflammation is partly responsible for the observed negative associations between obesity and HRQOL, and also whether systemic inflammation independently affects HRQOL. We conducted an exploratory analysis to investigate the relationships between obesity, systemic inflammation and indices of HRQOL, using NHANES survey data.MethodsData for the variables of interest were available for 6325 adults (aged 20–75 years, BMI > 18.5 kg/m2). Demographic, body mass index (BMI), C-reactive protein (CRP), inflammatory disease status, medication use, smoking, and HRQOL data were obtained from NHANES (2005–2008) and analyzed using sampling-weighted generalized linear models. Data was subjected to multiple imputation in order to mitigate information loss from survey non-response. Both main effects and interaction effects were analyzed to evaluate possible mediation or moderation effects. Model robustness was ascertained via sensitivity analysis. Averaged results from the imputed datasets were reported in as odds ratios (OR) and confidence intervals (CI).ResultsObesity was positively associated with poor physical healthy days (OR: 1.59, 95% CI: 1.15–2.21) in unadjusted models. ‘Elevated’ and ‘clinically raised’ levels of the inflammation marker CRP were also positively associated with poor physical healthy days (OR = 1.61, 95% CI: 1.23–2.12, and OR = 2.45, 95% CI: 1.84–3.26, respectively); additionally, ‘clinically raised’ CRP was positively associated with mental unhealthy days (OR = 1.66, 95% CI: 1.26–2.19). The association between obesity and physical HRQOL was rendered non-significant in models including CRP. Association between ‘elevated’ and ‘clinically raised’ CRP and physical unhealthy days remained significant even after adjustment for obesity or inflammation-modulating covariates (OR = 1.36, 95% CI: 1.02–1.82, and OR = 1.75, 95% CI: 1.21–2.54, respectively).ConclusionsSystemic inflammation appears to mediate the association between obesity and physical unhealthy days. Clinically raised inflammation is an independent determinant of physical and mental unhealthy days. Importantly, elevated (but sub-clinical) inflammation is also negatively associated with physical healthy days, and may warrant more attention from a population health perspective than currently appreciated.

Expression of CD73 and CD39 on Peripheral Blood Leukocytes in Type II Diabetes Patients

Background: Type II diabetes mellitus (T2D) is one of the most common chronic metabolic diseases. It is associated with a state of chronic inflammation resulting in both microvascular and macrovascular complications. The adinosinergic axis plays an important anti-inflammatory protective role through conversion of ATP (produced as a result of inflammation) into adenosine (a potent anti-inflammatory mediator) through CD39 and CD73. Various peripheral blood leucocytes hold CD39 and CD73 with different degrees. Objective: To determine the expression of CD73 and CD39 on different peripheral blood leukocytes including Treg cells to uncover their inflammatory modulation role in T2D subjects in comparison to normal control ones. The level of their expression will be correlated with various anthropometric and biochemical parameters in diabetic patients. Materials and Methods: Venous blood was collected on EDTA anticoagulated tubes from 45 T2D patients; 15 with early T2D and 30 with complicated T2D with both microvascular and macrovascular complications. Twenty-five normal subjects, with no family history of T2D, were included. Immunophenotyping of the samples were performed on Navios Flow cytometer (Coulter Electronics, USA), using phycoerythrin (PE)-labelled CD39 antibodies, fluorescein isothiocyanate (FITC)-labelled CD4 antibodies, peridinin-chlorophyll-protein complex: CY5.5 conjugate (PerCP-CY5.5)-labelled CD73 and allophycocyanin conjugate (APC)-labelled CD25. Results: CD39 expression was highest in early cases of T2D in comparison to least expression in complicated T2D on peripheral blood total lymphocytes, CD4+ lymphocytes and CD4+CD25+ lymphocytes. Conclusions: The increased expression of CD39 in early non-complicated cases of T2D indicates a state of low-level chronic inflammation owing to their role in production of adenosine; a potent anti-inflammatory mediator. This is reversed when CD39 expression in peripheral blood leucocytes is assessed in complicated T2D patients, which emphasise their role in protecting the patients from diabetic complications.

Expression of CD73 and CD39 on Peripheral Blood Leukocytes in Type II Diabetes Patients

Background: Type II diabetes mellitus (T2D) is one of the most common chronic metabolic diseases. It is associated with a state of chronic inflammation resulting in both microvascular and macrovascular complications. The adinosinergic axis plays an important anti-inflammatory protective role through conversion of ATP (produced as a result of inflammation) into adenosine (a potent anti-inflammatory mediator) through CD39 and CD73. Various peripheral blood leucocytes hold CD39 and CD73 with different degrees. Objective: To determine the expression of CD73 and CD39 on different peripheral blood leukocytes including Treg cells to uncover their inflammatory modulation role in T2D subjects in comparison to normal control ones. The level of their expression will be correlated with various anthropometric and biochemical parameters in diabetic patients. Materials and Methods: Venous blood was collected on EDTA anticoagulated tubes from 45 T2D patients; 15 with early T2D and 30 with complicated T2D with both microvascular and macrovascular complications. Twenty-five normal subjects, with no family history of T2D, were included. Immunophenotyping of the samples were performed on Navios Flow cytometer (Coulter Electronics, USA), using phycoerythrin (PE)-labelled CD39 antibodies, fluorescein isothiocyanate (FITC)-labelled CD4 antibodies, peridinin-chlorophyll-protein complex: CY5.5 conjugate (PerCP-CY5.5)-labelled CD73 and allophycocyanin conjugate (APC)-labelled CD25. Results: CD39 expression was highest in early cases of T2D in comparison to least expression in complicated T2D on peripheral blood total lymphocytes, CD4+ lymphocytes and CD4+CD25+ lymphocytes. Conclusions: The increased expression of CD39 in early non-complicated cases of T2D indicates a state of low-level chronic inflammation owing to their role in production of adenosine; a potent anti-inflammatory mediator. This is reversed when CD39 expression in peripheral blood leucocytes is assessed in complicated T2D patients, which emphasise their role in protecting the patients from diabetic complications.

The Bioactive Substance Secreted by MSC Retards Mouse Aortic Vascular Smooth Muscle Cells Calcification.

Background Vascular calcification, which is associated with low-level chronic inflammation, is a complication that occurs during aging, atherosclerosis, chronic kidney disease, diabetes mellitus, and hyperlipaemia. In this study, we used conditioned media from mesenchymal stem cells (MSC-CM), a source of autologous cytokines, to test the hypothesis that MSC-CM inhibits vascular smooth muscle cell (VSMC) calcification by suppressing inflammation and apoptosis. Methods VSMCs were treated with β-glycerophosphate (β-GP) to induce calcification and MSC-CM was used as a treatment. Calcium deposition was evaluated using alizarin red and von Kossa staining after a 7-day induction period. Intracellular calcium contents were measured via the o-cresolphthalein complexone method, and alkaline phosphatase (ALP) activity was determined using the para-nitrophenyl phosphate method. The expressions of specific-osteogenic markers, inflammatory cytokines, and apoptosis-associated genes/proteins were examined by real-time polymerase chain reaction or western blotting. Results MSC-CM inhibited β-GP-induced calcium deposition in VSMCs and decreased intracellular calcium content and ALP activity. Additionally, MSC-CM suppressed the β-GP-induced increases in BMP2, Msx2, Runx2, and osteocalcin expression. Additionally, MSC-CM decreased the expression of TNF-α, IL-1β, and IL-6 in VSMC. MSC-CM also partly blocked β-GP-induced VSMC apoptosis, which was associated with an increase in the Bcl-2/Bax expression ratio and a decrease in caspase-3 expression. Conclusion Our study results suggest that MSC-CM can inhibit VSMC calcification. This suggests a potential novel clinical application for MSCs in the treatment of vascular calcification and associated diseases.