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

2014 ◽  
Vol 112 (10) ◽  
pp. 1724-1734 ◽  
Author(s):  
Eirini C. Spyridaki ◽  
Panagiotis Simos ◽  
Pavlina D. Avgoustinaki ◽  
Eirini Dermitzaki ◽  
Maria Venihaki ◽  
...  

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.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiayu Huang ◽  
Lin Liu ◽  
Chunyan Chen ◽  
Ying Gao

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.


2007 ◽  
Vol 92 (12) ◽  
pp. 4569-4574 ◽  
Author(s):  
Christian Herder ◽  
Sophie Schneitler ◽  
Wolfgang Rathmann ◽  
Burkhard Haastert ◽  
Heiko Schneitler ◽  
...  

Abstract Context: Low-grade inflammation is associated with insulin resistance and precedes the onset of type 2 diabetes mellitus in adults, but there are no comparable data in youth. Objective: The objective of the study was to characterize the pattern of subclinical immune activation that is associated with indices of obesity and insulin resistance in youth and analyze whether this association is explained by obesity. Design: This was a cross-sectional study. Setting: Medical check-up of schoolchildren was conducted by the Public Health Office in Düsseldorf (Germany). Participants: Participants included 519 adolescents (mean age 15.5 ± 0.8 yr). Main Outcome Measures: Measures included body mass index (BMI) and waist circumference (WC) as indices of obesity; fasting glucose, insulin, and homeostasis model assessment of insulin resistance; serum concentrations of TNFα, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1, interferon-γ-inducible protein (IP)-10 and adiponectin as immunological variables. Results: In age-, sex-, and lipid-adjusted analyses, IL-6, IL-18, IP-10, and adiponectin (inversely) were associated with both BMI and WC (all P ≤ 0.002). None of the immune markers was related to glucose, but IL-6, IL-18, and adiponectin (inversely) were associated with insulin and homeostasis model assessment of insulin resistance in age- and sex-adjusted models. Adjustment for BMI or WC indicated that a considerable proportion of these associations may be mediated by obesity. Conclusions: We found that a differential low-grade immune activation is associated with parameters of obesity in adolescents. Moreover, there is evidence that IL-6, IL-18, IP-10, and adiponectin (inversely) are associated with insulin resistance and that these associations can mainly be attributed to obesity.


2010 ◽  
Vol 95 (7) ◽  
pp. 3392-3399 ◽  
Author(s):  
Alexander Viardot ◽  
Lisa Sze ◽  
Louise Purtell ◽  
Amanda Sainsbury ◽  
Georgina Loughnan ◽  
...  

Background: Subjects with Prader-Willi syndrome (PWS) have a reduced life expectancy due to cardiovascular disease. Increased systemic low-grade inflammation is postulated as a contributor, despite reported lower visceral fat mass and increased insulin sensitivity. Objectives: Our aim was to compare inflammatory markers and arterial stiffness in PWS and adiposity-matched obese control subjects. Design: We conducted a cross-sectional cohort study comparing 12 PWS subjects, 12 obese subjects matched for percentage body fat and central abdominal fat mass, and 10 healthy normal-weight subjects. Main Outcome Measures: Dual-energy x-ray absorptiometry was used to assess body composition, flow cytometry to quantify activation markers on immune cells, and ELISA for measurement of C-reactive protein, adiponectin, and IL-6. Insulin resistance was estimated by homeostasis model assessment and arterial stiffness by applanation tonometry. Results: PWS and obese subjects had similarly increased homeostasis model assessment and arterial stiffness. Nevertheless, PWS subjects showed significantly higher IL-6 (4.9 ± 1.0 vs. 2.5 ± 0.4 pg/ml; P = 0.02) and nonsignificantly higher C-reactive protein (10.5 ± 3.2 vs. 4.0 ± 1.0 ng/ml; P = 0.08). Neutrophil activation markers CD66b and CD11b were higher in PWS compared to obese subjects (P < 0.01), reflecting an activated innate immune system. These markers were positively related to central adiposity in lean and obese subjects (r = 0.49; P < 0.05), but not in PWS subjects. Conclusions: PWS subjects compared to adiposity-matched obese subjects demonstrate similar insulin resistance but increased low-grade inflammation. The dissociation of inflammation and central adiposity suggests that activation of innate immunity may be either a specific genetic feature of PWS or linked to the commonly associated obstructive sleep apnea syndrome, and might offer a treatment target to reduce cardiovascular disease.


2019 ◽  
Vol 3 (10) ◽  
pp. 1771-1783 ◽  
Author(s):  
Jani Liimatta ◽  
Pauliina Utriainen ◽  
Tomi Laitinen ◽  
Raimo Voutilainen ◽  
Jarmo Jääskeläinen

Abstract Context Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown. Objective To study cardiometabolic profile in adult women with previous PA. Design and participants Thirty women with PA and 41 control subjects were followed from prepuberty to young adulthood. Main outcome measures Prevalence of the metabolic syndrome (MetS) and clinical and biochemical cardiovascular risk factors. Results There were no differences in the prevalence of MetS or in any parameters indicating dyslipidemia, hypertension, hepatosteatosis, atherosclerosis, or low-grade inflammation between the study groups. However, prevalence of insulin resistance (IR; P = 0.014) and acanthosis nigricans (P = 0.010) was higher in the PA group. Neither fasting glucose nor insulin concentrations differed between the study groups, but HbA1c [adjusted for body mass index (BMI) P = 0.011] and Homeostatic Model Assessment of Insulin Resistance (P = 0.044; BMI-adjusted P = nonsignificant) were higher in the PA group. Although BMI and fat percentage were comparable between the study groups, the PA group had higher central fat mass than the control group. In the whole study population, MetS and IR were associated with greater adult fat mass, but no prepubertal factors predicting later IR were found. Conclusion PA does not seem to be associated with MetS, dyslipidemia, hypertension, atherosclerosis, or low-grade inflammation in young adult women. However, some women with PA may be at an increased risk of unfavorable glucose metabolism, which is associated with increased central adiposity at adult age rather than determined by prepubertal factors.


2021 ◽  
Vol 9 (1) ◽  
pp. e001975
Author(s):  
Nicolas Quezada ◽  
Ilse Valencia ◽  
Javiera Torres ◽  
Gregorio Maturana ◽  
Jaime Cerda ◽  
...  

IntroductionSystemic chronic low-grade inflammation has been linked to insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). NOD-like receptor protein 3 (NLRP3) inflammasome and its final product, interleukin (IL)-1β, exert detrimental effects on insulin sensitivity and promote liver inflammation in murine models. Evidence linking hepatic NLRP3 inflammasome, systemic IR and NASH has been scarcely explored in humans. Herein, we correlated the hepatic abundance of NLRP3 inflammasome components and IR and NASH in humans.Research design and methodsMetabolically healthy (MH) (n=11) and metabolically unhealthy (MUH) (metabolic syndrome, n=21, and type 2 diabetes, n=14) subjects were recruited. Insulin sensitivity (homeostatic model assessment of IR (HOMA-IR) and Oral Glucose Sensitivity (OGIS120)), glycemic (glycated hemoglobin), and lipid parameters were determined by standard methods. Plasma cytokines were quantified by Magpix. Hepatic NLRP3 inflammasome components were determined at the mRNA and protein levels by reverse transcription–quantitative PCR and western blot, respectively. Liver damage was assessed by histological analysis (Non-alcoholic Fatty Liver Disease Activity Score (NAS) and Steatosis, Inflammatory Activity, and Fibrosis (SAF) scores). IR and liver histopathology were correlated with NLRP3 inflammasome components as well as with liver and plasma IL-1β levels.ResultsBody Mass Index, waist circumference, and arterial hypertension frequency were significantly higher in MUH subjects. These patients also had increased high-sensitivity C reactive protein levels compared with MH subjects. No differences in the plasma levels of IL-1β nor the hepatic content of Nlrp3, apoptosis-associated speck-like (Asc), Caspase-1, and IL-1β were detected between MUH and MH individuals. MUH subjects had significantly higher NAS and SAF scores, indicating more severe liver damage. However, histological severity did not correlate with the hepatic content of NLRP3 inflammasome components nor IL-1β levels.ConclusionOur results suggest that NLRP3 inflammasome activation is linked neither to IR nor to the inflammatory status of the liver in MUH patients.


Author(s):  
Charmaine S. Tam ◽  
Leanne M. Redman

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).


2014 ◽  
Vol 18 (11) ◽  
pp. 2031-2040 ◽  
Author(s):  
Mariko Nakamoto ◽  
Hirokazu Uemura ◽  
Tohru Sakai ◽  
Sakurako Katsuura-Kamano ◽  
Miwa Yamaguchi ◽  
...  

AbstractObjectiveThe purpose of the present study was to examine the association between soya food consumption and insulin resistance using baseline data of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan.DesignThis cross-sectional study included 1274 subjects, aged 34–70 years at baseline, living in Tokushima Prefecture between 2008 and 2013. Fasting blood samples were collected and information on lifestyle characteristics including soya food intake and medical history were obtained using a structured self-administered questionnaire. The homeostasis model assessment of insulin resistance (HOMA-IR) was measured and those with HOMA-IR≥2·5 were defined as having insulin resistance. Multiple logistic regression models were used to analyse the association between soya product intake and the prevalence of insulin resistance.SettingRural communities located in Tokushima Prefecture, Japan, between 2008 and 2013.SubjectsA total of 1148 adults (565 men and 583 women), aged 34–70 years.ResultsThe frequency of intake of miso soup, total non-fried soya products and total soya products showed significant inverse dose–response relationships with insulin resistance, after adjustments for potential confounders. When soya product intake was calculated as soya protein and isoflavone, the odds ratios of insulin resistance decreased significantly as the estimated intake of soya protein increased. Furthermore, significant inverse dose–response relationships were observed for total non-fried soya products and total soya products, after adjustment for total vegetable or total fibre consumption.ConclusionsThe present results indicate that the intake of soya products and non-fried soya products is associated with reduced insulin resistance in the Japanese population.


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