Obesity-related Inflammatory Markers Research Articles

Effects of obesity-related inflammatory markers on psychosomatic manifestations of premenstrual tension syndrome: towards better therapeutic outcomes (An original article)

Background: Obesity-induced inflammation facilitates depression and premenstrual tension syndrome. Hypoxia is a common feature of inflammation. Hypoxia inducible factors adapt cells to low oxygen tension and inflammation. Objectives: We aimed to see how obesity, along with Amiloride, Hydrochlorothiazide, Metformin, calorie restriction, and walking exercise, affected psychosomatic characteristics of premenstrual tension syndrome, during a six-month period.Patients and methods: A prior ethical committee approval and informed patients’ consent were taken. This study was performed in Tanta University, Egypt from May 2019 to December 2019. This study aims at evaluating the effects of obesity-induced inflammatory mediators on psychosomatic effects in women having premenstrual tension syndrome. Effects of combined therapy using (Metformin, Amiloride. Hydrochloride/ Hydrochlorthiazide, caloric restriction, half an hour of walking exercise per day, and Vitazinc capsules) treatment was compared to the same combined therapy including Royal vitamin G treatment (instead of Vitazinc) on alleviating psychosomatic manifestations of premenstrual tension syndrome. Sixty obese women having premenstrual tension syndrome were categorized into younger age group (18-39 years) and older age (40-48 years) versus a non-obese age-matched control group. Body mass index in addition to serum tumour necrosis factor-α (TNF- α), hypoxia-inducible factor-1α (HIF-1α) and receptor activator of nuclear factor- kappa-Β ligand (RANKL) were assessed. Related psychosomatic manifestations of premenstrual tension syndrome (edema, anxiety, and fatigue) were also assessed. Results: Obesity significantly increased serum TNF-α (p < 0.01), HIF-1 α (p < 0.01) and RANKL (p < 0.01). Obesity-induced biochemical effects were higher in older obese women than younger ones. Obesity significantly exaggerated the severity of investigated psychosomatic manifestations (p < 0.001). Both combined therapies (including either Vitazinc or Royal vitamin G) significantly and dramatically decreased the percentage of cases having psychosomatic manifestations (p < 0.001) that was closely related to the decreased serum biochemical parameters. Conclusion: Combined therapy containing Royal vitamin G significantly improved serum biochemical parameters and psychosomatic manifestations better than combined therapy containing Vitazinc.

Increased levels of inflammatory plasma markers and obesity risk in a mouse model of Down syndrome.

Down syndrome (DS) is caused by the trisomy of human chromosome 21 and is the most common genetic cause of intellectual disability. In addition to the intellectual deficiencies and physical anomalies, DS individuals present a higher prevalence of obesity and subsequent metabolic disorders than healthy adults. There is increasing evidence from both clinical and experimental studies indicating the association of visceral obesity with a pro-inflammatory status and recent studies have reported that obese people with DS suffer from low-grade systemic inflammation. However, the link between adiposity and inflammation has not been explored in DS. Here we used Ts65Dn mice, a validated DS mouse model, for the study of obesity-related inflammatory markers. Ts65Dn mice presented increased energy intake, and a positive energy balance leading to increased adiposity (fat mass per body weight), but did not show overweight, which only was apparent upon high fat diet induced obesity. Trisomic mice also had fasting hyperglycemia and hypoinsulinemia, and normal incretin levels. Those trisomy-associated changes were accompanied by reduced ghrelin plasma levels and slightly but not significantly increased leptin levels. Upon a glucose load, Ts65Dn mice showed normal increase of incretins accompanied by over-responses of leptin and resistin, while maintaining the hyperglycemic and hypoinsulinemic phenotype. These changes in the adipoinsular axis were accompanied by increased plasma levels of inflammatory biomarkers previously correlated with obesity galectin-3 and HSP72, and reduced IL-6. Taken together, these results suggest that increased adiposity, and pro-inflammatory adipokines leading to low-grade inflammation are important players in the propensity to obesity in DS. We conclude that DS would be a case of impaired metabolic-inflammatory axis.

Abstract P301: The Association of Physical Activity and Inflammation is Independent of Central Obesity in the Multi-Ethnic Study of Atherosclerosis

Purpose: Physical activity is associated with decreased adiposity-related inflammation in adults. Whether this association is independent of central obesity is unknown but important for understanding the mechanisms associated with reducing cardiometabolic disease risk through physical activity. This study examined whether associations of physical activity and obesity-related inflammatory markers were independent of central adiposity. Methods: Between 2002 and 2005, 1970 participants from the Multi-Ethnic Study of Atherosclerosis completed detailed health history and physical activity questionnaires, underwent physical measurements including computed tomography to quantify abdominal visceral and subcutaneous fat, and measurements of adiponectin, leptin, interleukin-6, tumor necrosis factor-alpha, and resistin. Statistical analyses included analysis of covariance and multivariable-adjusted regression. Results: The mean (range) age of participants was 64.7 (55-84) years and 50% were female. After adjustment for age and sex, and compared to the lowest quartile, inflammatory markers in the highest quartile of moderate-to-vigorous physical activity were 16% higher for adiponectin and 30%, 26% and 9% lower for leptin, interleukin-6, and resistin, respectively (p&lt;0.05 for all). In linear regression adjusted for demographics, dyslipidemia, hypertension, diabetes, smoking, glomerular filtration rate, renin and aldosterone, each standard deviation increment of moderate-to-vigorous physical activity was associated with significantly higher levels of adiponectin (β=0.04) and lower levels of leptin (β=-0.06), interleukin-6 (β=-0.08), and resistin (β=-0.05, p&lt;0.05 for all). The associations with leptin, interleukin-6, and resistin were independent of total and central adiposity (p&lt;0.05), whereas the association between moderate-to-vigorous physical activity and adiponectin was attenuated by central adiposity (p&gt;0.05). There were no significant interactions by race/ethnicity or sex. Conclusions: Moderate-to-vigorous physical activity was associated with a more favorable profile of inflammatory markers, independent of relevant cardiometabolic disease risk factors including central obesity.

Physical Activity and Adiposity-related Inflammation: The MESA.

Physical activity is associated with decreased adiposity-related inflammation in adults. Whether this association is independent of central obesity is unknown but important for understanding the mechanisms associated with reducing cardiometabolic disease risk through physical activity. This study examined whether associations of physical activity and obesity-related inflammatory markers were independent of central adiposity. Between 2002 and 2005, 1970 participants from the Multi-Ethnic Study of Atherosclerosis completed detailed health history and physical activity questionnaires, underwent physical measurements including computed tomography to quantify abdominal visceral and subcutaneous fat, and measurements of adiponectin, leptin, interleukin-6, tumor necrosis factor-alpha, and resistin. Statistical analyses included analysis of covariance and multivariable-adjusted regression. The mean (range) age of participants was 64.7 (55-84) yr and 50% were women. After adjustment for age and sex, and compared with the lowest quartile, inflammatory markers in the highest quartile of moderate-to-vigorous physical activity were 16% higher for adiponectin and 30%, 26%, and 9% lower for leptin, interleukin-6, and resistin, respectively (P < 0.05 for all). In linear regression adjusted for demographics, dyslipidemia, hypertension, diabetes, smoking, glomerular filtration rate, renin, and aldosterone, each standard deviation increment of moderate-to-vigorous physical activity was associated with significantly higher levels of adiponectin (β = 0.04) and lower levels of leptin (β = -0.06), interleukin-6 (β = -0.08), and resistin (β = -0.05, P < 0.05 for all). The associations with leptin, interleukin-6, and resistin were independent of total and central adiposity (P < 0.05), whereas the association between moderate-to-vigorous physical activity and adiponectin was attenuated by central adiposity (P > 0.05). There were no significant interactions by race/ethnicity or sex. Moderate-to-vigorous physical activity was associated with a more favorable profile of inflammatory markers, independent of relevant cardiometabolic disease risk factors including central obesity.

High dietary calcium does not mediate the effects of dairy to attenuate weight gain and improve glucose tolerance in mice with pre‐existing obesity

Previous research in animal models suggests increased dietary Ca and dairy reduces weight gain and obesity‐associated inflammation. Effects of these dietary factors on obese phenotypes when introduced in the context of pre‐existing obesity are less clear. We investigated the effects of introducing high calcium (HC) and HC with non‐fat dry milk (NFDM) in adult male C57BL/6J mice pre‐fattened with an obesigenic, pro‐inflammatory high fat diet (45% kcal; HFD) for 12 wks. Mice were then assigned (n=30/group) to one of three macronutrient‐matched HF diets for an additional 8 wks: control (0.5%; CON), HC (1.5% Ca), or HC with NFDM. Surprisingly, HC mice gained more wt (10.1 + 0.5 g vs. 5.3 + 0.4 g; P&lt;0.001) with a significantly higher feed efficiency (12.8 + 0.5 mg wt gain/kcal intake) and decreased glucose tolerance (GT) compared to CON. NFDM mice gained the least wt (2.2 + 0.6g; P&lt;0.001) with a lower feed efficiency (3.0 + 0.6 vs. 7.8 + 0.4 mg wt gain/kcal intake) and improved GT vs. CON. Obesity‐related inflammatory markers are currently being analyzed. We conclude that effects of dairy to reduce weight gain and improve glucose tolerance in mice with pre‐existing obesity and fed a HFD is not mediated by dietary Ca, and likely results from other factors specific to the NFDM diet.Grant Funding Source: National Dairy Council and ARS Project 5306–51530–016–00D

Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Background: The fat mass and obesity associated (FTO) gene has been found to contribute to the risk of obesity in humans, but the function and regulation of FTO mRNA expression in adipose tissues remain to be clarified. Our aims were to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese women and its relation with obesity, insulin resistance indices, and most importantly, to obesity-related inflammatory markers. Methods: Paired subcutaneous and visceral fat were excised from 33 morbidly obese women and 12 control women who underwent bariatric surgery by laparoscopic gastric by-pass and elective surgery respectively. Adipose tissue mRNA expression was determined by real time RT-PCR. Results: FTO mRNA expression in visceral adipose tissue (VAT) was significantly higher than in subcutaneous adipose tissue (SAT) from obese but not control patients. SAT FTO expression was reduced in obese women compared to control subjects. It correlated negatively with BMI and insulin resistance indices. FTO expression in SAT was positively related to both circulating and mRNA levels of adiponectin, to adiponectin receptor and to PPAR-Δexpression, but negatively with IL-6 gene expression and with circulating levels of leptin. FTO in VAT was also positively correlated with adiponectin, adiponectin receptor and PPAR-Δ mRNA expression. Conclusion: FTO expression in subcutaneous adipose tissue negatively correlates with obesity and insulin resistance. On the other hand, FTO presents a positive association with the expression of adiponectin, an anti-inflammatory adipokine, and with PPAR-Δ in both adipose tissues. Taken together, our results suggest that FTO is associated with an anti-inflammatory behaviour in morbid obesity.

Parallel downregulation of retinol-binding protein-4 and adiponectin expression in subcutaneous adipose tissue of non-morbidly obese subjects

Adipokines are involved in the etiopathology of obesity-related disorders. Since the role of adipokine retinol-binding protein-4 (RBP4) in obesity remains uncertain and its relationship with other adipokines and inflammatory markers has not been examined in detail, we investigated the relationships of RBP4 mRNA expression and circulating protein levels with obesity, anthropometric and metabolic variables, as well as with obesity-related inflammatory markers adiponectin and C-reactive protein. One-hundred and twenty-five subjects participated, 36 lean (body mass index (BMI): <25 kg/m(2)) and 89 obese (overweight/obese; BMI: > or =25<40) whose anthropometric and metabolic variables were assessed. mRNA expression was quantified by real-time PCR in subcutaneous adipose tissue (s.c.-AT) of 46 subjects. There was a tendency for circulating RBP4 levels to positively correlate with waist circumference (beta=0.29, P=0.08; R(2)=0.08), but there was no significant association with the obesity-related parameters analysed. RBP4 and adiponectin mRNA expression levels were similarly downregulated in the s.c.-AT of obese subjects (0.5-fold); however, RBP4 downregulation did not affect its circulating protein levels. The expression of RBP4 and adiponectin was positively correlated even after controlling for confounding factors (beta=0.59, P<0.0001; R(2)=0.40). In our population, RBP4 circulating levels were not significantly correlated with obesity-related parameters, although a tendency to correlate with waist circumference suggests a relationship with insulin resistance and other metabolic disorders. In addition, our results suggest that the production of RBP4 by other tissues such as liver, rather than s.c.-AT, may be involved in regulating RBP4 circulating levels.

Adiposity affects human response to inhaled organic dust

Swine containment facilities are often highly contaminated with organic dusts that often contain varying levels of endotoxins and other microbial products. This study was performed to evaluate the effect of obesity on the inflammatory response induced by chronic or acute exposure to swine confinement buildings (SCB). Two separate studies were performed; Study I included 36 SCB long-time workers and a control group of 35 matched male hospital workers never exposed to SCB. In Study II, 14 naïve healthy young subjects (8 overweight and 6 lean) volunteered to be acutely exposed to a SCB environment for 5 hr. Markers of sub-clinical inflammation linked to obesity (C-reactive protein (CRP), interleukin 6 (IL-6)) or to active inflammation (soluble adhesion molecules, IL-8, TNF) were measured. In the first study, positive correlations were found between girth circumference and serum levels of IL-6 (r = 0.57, P = 0.0003) and CRP (r = 0.62, P < 0.0001) in the control group. These correlations were however blunted or lost in the SCB workers group who showed positive correlations between girth circumference and soluble l-selectin (r = 0.34, P = 0.04), TNFalpha (r = 0.37, P = 0.03), ICAM-1 (r = 0.61, P < 0.0001). In the second study involving acute SCB exposure of naïve volunteers, no significant differences were observed between normal weight and overweight subjects for white blood cells, nasal lavage cell counts, and IL-8 levels. However, higher levels of CRP, TNF, and IL-6 were detected in overweight volunteers compared to those who were lean. In pig farmers (Study I), environmentally induced chronic inflammation appears to blunt the sub-clinical inflammation linked to obesity, whereas in naïve volunteers of Study II, environmentally induced acute inflammation seems to have a potentiating effect on obesity-related inflammatory markers.

Leisure-time physical activity and reduced plasma levels of obesity-related inflammatory markers.

This study investigated the relationship between physical activity and the obesity-related inflammatory markers C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptors (sTNF-Rs) 1 and 2. Furthermore, we examined the relationship between physical activity and insulin sensitivity (insulin, C-peptide, and hemoglobin A(1c) levels) and whether inflammatory markers mediate this association. Biomarkers were measured in 405 healthy men and 454 healthy women from two large ongoing prospective studies. Information about physical activity and other variables was assessed by questionnaires. After adjustment for other predictors of inflammation, physical activity was inversely associated with plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein (p = 0.07, p = 0.004, p = 0.04, and p = 0.009). After further adjustment for BMI and leptin, as a surrogate for fat mass, most of these associations were no longer significant. Physical activity was also inversely related to insulin and C-peptide levels (p = 0.008 and p < 0.001); however, in contrast to BMI and leptin, levels of inflammatory markers explained only very little of this inverse relationship. These results suggest that frequent physical activity is associated with lower systemic inflammation and improved insulin sensitivity. These associations can partially be explained by a lower degree of obesity in physically active subjects. Although inflammatory markers may mediate obesity-dependent effects of physical activity on inflammatory related diseases such as type 2 diabetes or coronary heart disease, our study suggests that they do not directly account for the beneficial effects of physical activity on insulin resistance.