Activation of the ROS/TXNIP/NLRP3 pathway disrupts insulin-dependent glucose uptake in skeletal muscle of insulin-resistant obese mice.

Oxidative stress and the activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome have been linked to insulin resistance in skeletal muscle. In immune cells, the exacerbated generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome, by facilitating the interaction between thioredoxin interacting protein (TXNIP) and NLRP3. However, the precise role of ROS/TXNIP-dependent NLRP3 inflammasome activation in skeletal muscle during obesity-induced insulin resistance remains undefined. Here, we induced insulin resistance in C57BL/6J mice by feeding them for 8 weeks with a high-fat diet (HFD) and explored whether the ROS/TXNIP/NLRP3 pathway was involved in the induction of insulin resistance in skeletal muscle. Skeletal muscle fibers from insulin-resistant mice exhibited increased oxidative stress, as evidenced by elevated malondialdehyde levels, and altered peroxiredoxin 2 dimerization. Additionally, these fibers displayed augmented activation of the NLRP3 inflammasome, accompanied by heightened ROS-dependent proximity between TXNIP and NLRP3, which was abolished by the antioxidant N-acetylcysteine (NAC). Inhibition of the NLRP3 inflammasome with MCC950 or suppressing the ROS/TXNIP/NLRP3 pathway with NAC restored insulin-dependent glucose uptake in muscle fibers from insulin-resistant mice. These findings provide insights into the mechanistic link between oxidative stress, NLRP3 inflammasome activation, and obesity-induced insulin resistance in skeletal muscle.

The Placental Role in Gestational Diabetes Mellitus: A Molecular Perspective.

During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro-inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children.

Resolution of inflammation in chronic disease via restoration of the heat shock response (HSR).

Effective resolution of inflammation via the heat shock response (HSR) is pivotal in averting the transition to chronic inflammatory states. This transition characterizes a spectrum of debilitating conditions, including insulin resistance, obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular ailments. This manuscript explores a range of physiological, pharmacological, and nutraceutical interventions aimed at reinstating the HSR in the context of chronic low-grade inflammation, as well as protocols to assess the HSR. Monitoring the progression or suppression of the HSR in patients and laboratory animals offers predictive insights into the organism's capacity to combat chronic inflammation, as well as the impact of exercise and hyperthermic treatments (e.g., sauna or hot tub baths) on the HSR. Interestingly, a reciprocal correlation exists between the expression of HSR components in peripheral blood leukocytes (PBL) and the extent of local tissue proinflammatory activity in individuals afflicted by chronic inflammatory disorders. Therefore, the Heck index, contrasting extracellular 70 kDa family of heat shock proteins (HSP70) (proinflammatory) and intracellular HSP70 (anti-inflammatory) in PBL, serves as a valuable metric for HSR assessment. Our laboratory has also developed straightforward protocols for evaluating HSR by subjecting whole blood samples from both rodents and human volunteers to ex vivo heat challenges. Collectively, this discussion underscores the critical role of HSR disruption in the pathogenesis of chronic inflammatory states and emphasizes the significance of simple, cost-effective tools for clinical HSR assessment. This understanding is instrumental in the development of innovative strategies for preventing and managing chronic inflammatory diseases, which continue to exert a substantial global burden on morbidity and mortality.

Supplementation with EPA and DHA omega-3 fatty acids improves peripheral immune cell mitochondrial dysfunction and inflammation in subjects with obesity.

Omega-3 fatty acids (w-3 FA) have anti-inflammatory effects and improve mitochondrial function. Nonetheless, little is known about their effect on mitochondrial bioenergetics of peripheral blood mononuclear cells (PBMCs) in individuals with obesity. Thus, this study aimed to determine the mitochondrial bioenergetics status and cell subset composition of PBMCs during obesity, before and after 1 month supplementation with w-3 FA. We performed a case-control study with twelve women with normal BMI (lean group) and 19 with grade 2 obesity (obese group), followed by a before-after prospective study where twelve subjects with obesity received a 1 month intervention with 5.25 g of w-3 FA (3.5 g eicosapentaenoic (EPA) and 1.75 g docosahexaenoic (DHA) acids), and obtained PBMCs from all participants. Mitochondrial bioenergetic markers, including basal and ATP-production associated respiration, proton leak, and nonmitochondrial respiration, were higher in PBMCs from the obese group vs. the lean group. The bioenergetic health index (BHI), a marker of mitochondrial function, was lower in the obese vs. the lean group. In addition, Th1, Th2, Th17, CD4+ Tregs, CD8+ Tregs, and Bregs, M1 monocytes and pDCreg cells were higher in PBMCs from the obese group vs. the lean group. The w-3 FA intervention improved mitochondrial function, mainly by decreasing nonmitochondrial respiration and increasing the reserve respiratory capacity and BHI. The intervention also reduced circulating pro-inflammatory and anti-inflammatory lymphocyte and monocytes subsets in individuals with obesity. The mitochondrial dysfunction of PBMCs and the higher proportion of peripheral pro-inflammatory and anti-inflammatory immune cells in subjects with obesity, improved with 1 month supplementation with EPA and DHA.

Virulence Factors of the Gut Microbiome Are Associated with BMI and Metabolic Blood Parameters in Children with Obesity.

The development of metabolic diseases is linked to the gut microbiota. A cross-sectional study involving 45 children (6 to 12 years old) was conducted to investigate the relationship between gut microbiota and childhood obesity. Anthropometric and metabolic measurements, food-frequency questionnaires (FFQs), and feces samples were obtained. Using the body mass index (BMI) z-score, we categorized each participant as normal weight (NW), or overweight and obese (OWOB). We determined 2 dietary profiles: one with complex carbohydrates and proteins (pattern 1), and the other with saturated fat and simple carbohydrates (pattern 2). The microbial taxonomic diversity and metabolic capacity were determined using shotgun metagenomics. We found differences between both BMI groups diversity. Taxa contributing to this difference, included Eubacterium sp., Faecalibacterium prausnitzii, Dialister, Monoglobus pectinilyticus, Bifidobacterium pseudocatenulatum, Intestinibacter bartlettii, Bacteroides intestinalis, Bacteroides uniformis, and Methanobrevibacter smithii. Metabolic capacity differences found between NW and OWOB, included the amino acid biosynthesis pathway, the cofactor, carrier, and vitamin biosynthesis pathway, the nucleoside and nucleotide biosynthesis and degradation pathways, the carbohydrate-sugar degradation pathway, and the amine and polyamine biosynthesis pathway. We found significant associations between taxa such as Ruminococcus, Mitsuokella multacida, Klebsiella variicola, and Citrobacter spp., metabolic pathways with the anthropometric, metabolic, and dietary data. We also found the microbiome's lipooligosaccharide (LOS) category as differentially abundant between BMI groups. Metabolic variations emerge during childhood as a result of complex nutritional and microbial interactions, which should be explained in order to prevent metabolic illnesses in adolescence and maturity. IMPORTANCE The alteration of gut microbiome composition has been commonly observed in diseases involving inflammation, such as obesity and metabolic impairment. Inflammatory host response in the gut can be a consequence of dietary driven dysbiosis. This response is conducive to blooms of particular bacterial species, adequate to survive in an inflammatory environment by means of genetical capability of utilizing alternative nutrients. Understanding the genomic and metabolic contribution of microbiota to inflammation, including virulence factor prevalence and functional potential, will contribute to identifying modifiable early life exposures and preventive strategies associated with obesity risk in childhood.

Morphological Assessment and Biomarkers of Low-Grade, Chronic Intestinal Inflammation in Production Animals.

The complex interaction between the intestinal mucosa, the gut microbiota, and the diet balances the host physiological homeostasis and is fundamental for the maximal genetic potential of production animals. However, factors such as chemical and physical characteristics of the diet and/or environmental stressors can continuously affect this balance, potentially inducing a state of chronic low-grade inflammation in the gut, where inflammatory parameters are present and demanding energy, but not in enough intensity to provoke clinical manifestations. It's vital to expand the understanding of inflammation dynamics and of how they compromise the function activity and microscopic morphology of the intestinal mucosa. These morphometric alterations are associated with the release of structural and functional cellular components into the feces and the blood stream creating measurable biomarkers to track this condition. Moreover, the identification of novel, immunometabolic biomarkers can provide dynamic and predictors of low-grade chronic inflammation, but also provide indicators of successful nutritional or feed additive intervention strategies. The objective of this paper is to review the mechanisms of low-grade inflammation, its effects on animal production and sustainability, and the biomarkers that could provide early diagnosis of this process and support studies of useful interventional strategies.

The immune response as a therapeutic target in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public health problem worldwide. The clinical progression of NAFLD is associated with advanced forms of liver injury such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). As such, diverse pharmacological strategies have been implemented over the last few years, principally focused on metabolic pathways involved in NAFLD progression. However, a variable response rate has been observed in NAFLD patients, which is explained by the interindividual heterogeneity of susceptibility to liver damage. In this scenario, it is necessary to search for different therapeutic approaches. It is worth noting that chronic low-grade inflammation constitutes a central mechanism in the pathogenesis and progression of NAFLD, associated with abnormal composition of the intestinal microbiota, increased lymphocyte activation in the intestine and immune effector mechanisms in liver. This review aims to discuss the current knowledge about the role of the immune response in NAFLD development. We have focused mainly on the impact of altered gut-liver-microbiota axis communication on immune cell activation in the intestinal mucosa and the role of subsequent lymphocyte homing to the liver in NAFLD development. We further discuss novel clinical trials that addressed the control of the liver and intestinal immune response to complement current NAFLD therapies.

The influence of parental high-fat high-sugar diet on the gut-brain axis in male offspring.

PURPOSE: The gut-brain axis (GBA) is implicated in the development of obesity, and its role in developmental programming needs to be explored. This study uncovers the effects of a parental high-fat, high-sugar diet (HFS) on the gut (colon) and brain (hypothalamus) GBA of male Wistar rat offspring at weaning until adulthood. METHODS: For ten weeks before mating, male progenitors were fed a control diet (CD) or HFS, whereas dams were fed CD or HFS during pregnancy and lactation. Male offspring aged 21-and 90-day old were assessed for: Gene expression of toll-like receptor 4 (TLR4) pathway and zonula occludens 1 (ZO1) in the colon and hypothalamus; hypothalamic gene expression of orexigenic neuropeptides and Leptin receptor; serum levels of lipopolysaccharide (LPS), glucagon like peptide 1 (GLP-1), Ghrelin and neuropeptide Y (NPY); colonic cytokine levels; FaecalBifidobacterium spp.andLactobacillus spp. DNA. RESULTS: Paternal HFS showed increased endotoxaemia, reduced colonic gene expression of ZO1 and reduced colonic TNF-α at weaning. In the adult offspring, paternal HFS showed increased NPY, reduced serum Ghrelin, colonic pro-inflammatory cytokines, and lower faecalBifidobacteriumspp. DNA. Maternal diet showed increased hypothalamic gene expression of myeloid differentiation primary response 88 (MYD88) at weaning. The maternal HFS diet showed increased NPY and reduced faecalBifidobacteriumspp. andLactobacillusspp. DNA in the adult offspring. The combined effect of parental diet showed increased NPY at weaning, and lowerBifidobacteriumspp. andLactobacillus spp.in the adult offspring. CONCLUSION: Maternal and paternal HFS diet seem to influence the programming of the gut-brain axis, leading to increased visceral adiposity and weight of male offspring at weaning, the effect that lasted until adulthood.

Parental high-fat high-sugar diet programming and hypothalamus adipose tissue axis in male Wistar rats.

PURPOSE: Maternal nutrition during early development and paternal nutrition pre-conception can programme offspring health status. Hypothalamus adipose axis is a target of developmental programming, and paternal and maternal high-fat, high-sugar diet (HFS) may be an important factor that predisposes offspring to develop obesity later in life. This study aims to investigate Wistar rats' maternal and paternal HFS differential contribution on the development, adiposity, and hypothalamic inflammation in male offspring from weaning until adulthood. METHODS: Male progenitors were fed a control diet (CD) or HFS for 10 weeks before mating. After mating, dams were fed CD or HFS only during pregnancy and lactation. Forming the following male offspring groups: CD-maternal and paternal CD; MH-maternal HFS and paternal CD; PH-maternal CD and paternal HFS; PMH-maternal and paternal HFS. After weaning, male offspring were fed CD until adulthood. RESULTS: Maternal HFS diet increased weight, visceral adiposity, and serum total cholesterol levels, and decreased hypothalamic weight in weanling male rats. In adult male offspring, maternal HFS increased weight, glucose levels, and hypothalamic NFκBp65. Paternal HFS diet lowered hypothalamic insulin receptor levels in weanling offspring and glucose and insulin levels in adult offspring. The combined effects of maternal and paternal HFS diets increased triacylglycerol, leptin levels, and hypothalamic inflammation in weanling rats, and increased visceral adiposity in adulthood. CONCLUSION: Male offspring intake of CD diet after weaning reversed part of the effects of parental HFS diet during the perinatal period. However, maternal and paternal HFS diet affected adiposity and hypothalamic inflammation, which remained until adulthood.

Dietary AGEs as Exogenous Boosters of Inflammation.

Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated).

Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can levothyroxine replacement therapy mitigate the burden?

PURPOSE: This series of meta-analyses were aimed to elucidate the impact of hypothyroidism on low-grade systemic inflammation and oxidative stress assessed by C-reactive protein (CRP) and malondialdehyde (MDA) respectively; and to evaluate the effect of levothyroxine replacement therapy (LRT) on those outcomes. METHODS: PubMed database and the key studies references were searched prior to March 3, 2020. Data on serum or plasma CRP and MDA levels in SHT (subclinical) and/or OHT (overt) hypothyroid patients and controls were extracted to compute overall standardized mean differences (SMD) by the random-effects model. RESULTS: A total of 93 studies were entered into analyses and ten main meta-analyses were performed. OHT (SMD = 0.72 [0.39; 1.04], k = 35), SHT (SMD = 1.58 [0.78; 2.38], k = 56) and even mild SHT (TSH < 10 mU/L, SMD = 2.19 [0.02; 4.37], k = 13) proved to have a detrimental effect on CRP levels. LRT showed a favorable effect on CRP levels, particularly in OHT (SMD = -0.30 [-0.57; -0.02], k = 17). Increased levels of MDA were also found, especially in OHT (SMD = 2.49 [0.66; 4.31], k = 13). LRT may also improve MDA levels; however future studies would further validate the advantageous effect of LRT in hypothyroidism. Heterogeneity primarily originated from different study designs and geographic locations. CONCLUSION: Overall, these meta-analyses reveal that screening for hs-CRP and MDA in hypothyroid patients as simple biomarkers of low-grade systemic inflammation and oxidative stress may become a useful tool to identify those at increased risk who may benefit most from early interventions.

Pituitary neuroendocrine tumors and differentiated thyroid cancer: do metabolic and inflammatory risk factors play roles?

PURPOSE: It is postulated that patients with different types of pituitary neuroendocrine tumors (PitNETs) may present a higher incidence of cancer. Factors underlying individuals becoming overweight, such as insulin resistance, hyperleptinemia, and low-grade inflammation, may play a role in the risk of differentiated thyroid carcinoma (DTC) in such patients. This study aimed to investigate the frequency of and obesity-related risk factors associated with DTC in patients with PitNETs. METHODS: This cross-sectional study involved 149 patients with nonacromegalic PitNETs (AG group), 71 patients with acromegaly (ACRO group), and 156 controls (CG group). All participants underwent insulin and blood glucose measurements with the determination of the homeostatic model assessment-insulin resistance (HOMA-IR) index, leptin, and high-sensitivity C-reactive protein (hsCRP), and they also underwent thyroid ultrasound. Clinically significant nodules were biopsied for subsequent cytopathological evaluation, and participants were operated on when indicated. RESULTS: Patients in the AG group had high levels of insulin resistance and significantly higher levels of leptin and hsCRP compared with those of patients in the ACRO group. There were no cases of DTC in the AG group; two findings, one incidental, of DTC occurred in the CG group, and three cases of DTC were present in the ACRO group. Acromegaly was associated with DTC after adjusted analysis. CONCLUSIONS: Our findings in patients with nonacromegalic PitNETs do not indicate a high risk for DTC despite the presence of metabolic and inflammatory risk factors for neoplastic events. In contrast, acromegaly promotes a greater risk of DTC.

Endurance Exercise Mitigates Immunometabolic Adipose Tissue Disturbances in Cancer and Obesity.

Adipose tissue is considered an endocrine organ whose complex biology can be explained by the diversity of cell types that compose this tissue. The immune cells found in the stromal portion of adipose tissue play an important role on the modulation of inflammation by adipocytokines secretion. The interactions between metabolic active tissues and immune cells, called immunometabolism, is an important field for discovering new pathways and approaches to treat immunometabolic diseases, such as obesity and cancer. Moreover, physical exercise is widely known as a tool for prevention and adjuvant treatment on metabolic diseases. More specifically, aerobic exercise training is able to increase the energy expenditure, reduce the nutrition overload and modify the profile of adipocytokines and myokines with paracrine and endocrine effects. Therefore, our aim in this review was to cover the effects of aerobic exercise training on the immunometabolism of adipose tissue in obesity and cancer, focusing on the exercise-related modification on adipose tissue or immune cells isolated as well as their interaction.

Pathways linking obesity to neuropsychiatric disorders.

Obesity has been associated with cognitive and behavioral syndromes. Individuals who are obese have higher risk for developing neuropsychiatric disorders such as depression and dementia than non-obese. Conversely, patients with neuropsychiatric conditions may exhibit some features that contribute to obesity development such as unhealthy behaviors and treatment with drugs that increase appetite. This review addresses the multiple pathways implicated in the relationship between obesity and neuropsychiatric disorders, mainly mood disorders, schizophrenia, and major neurocognitive disorder or dementia. Both obesity and neuropsychiatric disorders are characterized by a low-grade systemic inflammation and neuroinflammation. Obesity is frequently accompanied by neuroendocrine changes, particularly involving the hypothalamic-pituitary-adrenal (HPA) axis. Indeed, activation of the stress system is commonly seen as a trigger for mood episodes, psychosis exacerbation, and cognitive decline. Growing evidence suggests the role of gut microbiota in obesity and brain functioning through the modulation of the inflammatory response and HPA axis. Owing to the intricate relationship between obesity and neuropsychiatric disorders, tackling one of them may affect the other. Therefore, a better understanding of the pathways underlying the link between obesity and neuropsychiatric disorders can contribute to the development of therapeutic strategies for these conditions.

Irritable bowel syndrome: a review of the general aspects and the potential role of vitamin D.

INTRODUCTION: Irritable Bowel Syndrome (IBS) is a bowel disorder leading to symptoms such as abdominal pain, modifications in the motility and bowel habits, distention, bloating, and gas. Vitamin D (VD) may interfere in a plethora of cellular mechanisms, and act directly or indirectly in the regulation of the microbiome, the release of anti-microbial peptides, modulation of the immune system and inflammation processes; which in turn, may positively interfere with the altered gut function. The main purpose of this review was to survey studies involving the impacts of VD on IBS. Area covered: Eligible studies including the term VD and IBS were searched in the MEDLINE-PubMed and EMBASE (2009-2018). VD may act direct or indirectly in the regulation of the gut microbiome, immune response, and psychosocial factors that may be included in the list of IBS triggering factors. Expert opinion: Once VD plays an essential role in many processes associated with IBS, its deficiency may be associated with IBS, and the supplementation could help in the therapeutic approach for this condition. For these reasons, the understanding of the association of VD in IBS is indispensable for the development of new strategies that could improve the quality of life of the patient.

Adipose tissue inflammation and metabolic syndrome. The proactive role of probiotics.

PURPOSE: The first part of this review focuses on the role of cells and molecules of adipose tissue involved in metabolic syndrome-induced inflammation and in the maintenance of this pathology. In the second part of the review, the potential role of probiotics-modulating metabolic syndrome-related inflammatory components is summarized and discussed. METHODS: The search for the current scientific literature was carried out using ScienceDirect, PubMed, and Google Scholar search engines. The keywords used were: metabolic syndrome, obesity, insulin resistant, adipose tissue, adipose tissue inflammation, chronic low-grade inflammation, immune cells, adipokines, cytokines, probiotics, and gut microbiota. RESULTS AND CONCLUSIONS: Chronic low-grade inflammation that characterized metabolic syndrome can contribute to the development of the metabolic dysfunctions involved in the pathogenesis of its comorbidities. Adipose tissue is a complex organ that performs metabolic and immune functions. During metabolic syndrome, an imbalance in the inflammatory components of adipose tissue (immune cells, cytokines, and adipocytokines), which shift from an anti-inflammatory to a pro-inflammatory profile, can provoke metabolic syndrome linked complications. Further knowledge concerning the immune function of adipose tissue may contribute to finding better alternatives for the treatment or prevention of such disorders. The control of inflammation could result in the management of many of the pathologies related to metabolic syndrome. Due to the strong evidence that gut microbiota composition plays a role modulating the body weight, adipose tissue, and the prevalence of a low-grade inflammatory status, probiotics emerge as valuable tools for the prevention of metabolic syndrome and health recovery.

Association between high-density lipoprotein subfractions and low-grade inflammation, insulin resistance, and metabolic syndrome components: The ELSA-Brasil study.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) can be divided into subfractions, which may have variable effects in atherogenesis. The results about the association between HDL-C subfractions and risk factors for cardiovascular disease are mixed. OBJECTIVE: The objective of this study was to analyze the association between HDL-C subfractions and each metabolic syndrome component, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and C-reactive protein (CRP). METHODS: Four thousand five hundred thirty-two individuals between 35 and 74 years old without previous manifest cardiovascular disease not using fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (vertical auto profile-in mg/dL) into HDL2-C and HDL3-C. HDL2-C/HDL3-C ratio, HOMA-IR, and high-sensitivity CRP were also included in the analysis. RESULTS: Mean age of participants was 51 ± 9 years, and 54.8% were women. In univariate analysis, HDL-C, HDL2-C, and HDL3-C were all inversely associated with each of the metabolic syndrome defining factors, HOMA-IR values, and serum CRP. We also observed a negative association between HDL2-C/HDL3-C ratio with the variables aforementioned even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (P < .01). CONCLUSION: HDL-C and its subfractions (HDL2-C and HDL3-C) are inversely associated with the defining features of metabolic syndrome, insulin resistance, and systemic inflammation. In addition, the HDL2-C/HDL3-C ratio measured by vertical auto profile is significantly associated with the former factors even after comprehensive adjustment for HDL-C and other confounding variables.

Resistance training reduces metabolic syndrome and inflammatory markers in older women: A randomized controlled trial.

BACKGROUND: This study analyzed the effects of a 12-week resistance training (RT) program without dietary interventions on metabolic syndrome (MetS) components and inflammatory biomarkers in older women. METHODS: Fifty-three older women (mean [±SD] age 70.4 ± 5.7 years; mean body mass index 26.7 ± 4.0 kg/m2 ) were randomly assigned to a training group (TG; n = 26) that performed 12 weeks of an RT program or a control group (CG; n = 27) that did not perform any type of physical exercise over the same period. Body composition (dual energy X-ray absorptiometry), muscular strength (one-repetition maximum tests), blood pressure (BP), and blood sample measurements were performed before and after intervention. RESULTS: After the 12-week period, there were significantly reductions (P < 0.05) in glucose levels (-20.4% vs -0.3%), waist circumference (-1.5% vs +2.0%), and systolic BP (-6.2% vs +0.9%), and complete normalization of MetS prevalence (18% at baseline vs. 0% after 12-weeks RT) in the TG. Moreover, C-reactive protein and tumor necrosis factor-α concentrations decreased in the TG (-28.6% and -21.6%, respectively), but increased in the CG (+34.5% and +13.3%, respectively). In addition there were positive improvements in the MetS Z-score in the TG but not CG (-21.6% vs +13.3%, respectively). CONCLUSION: The results suggest that a 12-week RT program seems to effectively reduce MetS components and inflammatory biomarkers in older women, regardless of dietary intervention. The RT-induced adaptations in body composition and inflammatory biomarkers appear to be related to healthy adaptations in risk factors for MetS.

The inflammation paradox: Why are Tsimane protected against Western diseases while Westerners are not?

We here describe two apparent paradoxes concerning high CRP levels and NCD risk. One has emerged from observational studies in the Amazon region showing that the indigenous Tsimane in Bolivia appear protected against non-communicable diseases (NCDs) such as obesity, type 2 diabetes, and cardiovascular diseases despite increased inflammatory markers. These findings stand in contrast to Western societies, where an increasing body of evidence demonstrates that low-grade-inflammation is the driver of NCDs. The second paradox has emerged from two field studies (Eifel studies) conducted in 2013 and 2014 with Westerners who returned to a simulated Palaeolithic lifestyle in a National park for 4 days. We had detected elevated inflammation markers, despite otherwise anti-inflammatory effects of these interventions as indicated by metabolic blood parameters. We here propose three hypotheses for this second inflammatory paradox.

Hypomagnesemia and its relation with chronic low-grade inflammation in obesity / Hipomagnesemia e sua relação com a inflamação crônica de baixo grau na obesidade

Summary Introduction: The accumulation of visceral fat in obesity is associated with excessive production of proinflammatory adipokines, which contributes to low-grade chronic inflammation state. Moreover, the literature has shown that mineral deficiency, in particular of magnesium, has important role in the pathogenesis of this metabolic disorder with relevant clinical repercussions. Objective: To bring updated information about the participation of hypomagnesemia in the manifestation of low-grade chronic inflammation in obese individuals. Method: Articles published in PubMed, SciELO, LILACS and ScienceDirect, using the following keywords: "obesity," "magnesium" and "low grade inflammation." Results: Scientific evidence suggests that magnesium deficiency favors the manifestation of low-grade chronic inflammation in obese subjects. Conclusion: From literature data, it is evident the participation of magnesium through biochemical and metabolic reactions in protecting against this metabolic disorder present in obesity.

Resumo Introdução: O acúmulo de gordura visceral na obesidade está associado à produção excessiva de adipocinas pró-inflamatórias, o que contribui para o estado de inflamação crônica de baixo grau. A literatura também tem mostrado que a deficiência de minerais, em particular do magnésio, possui papel importante na patogênese desse distúrbio metabólico com repercussões clínicas relevantes. Objetivo: Trazer informações atualizadas sobre a participação da hipomagnesemia na inflamação crônica de baixo grau em indivíduos obesos. Método: Bases de dados Pubmed, SciELO, Lilacs e ScienceDirect, utilizando as palavras-chave: "obesity", "magnesium" e "low grade inflammation". Resultados: As evidências científicas sugerem que a deficiência de magnésio favorece a manifestação da inflamação crônica de baixo grau em indivíduos obesos. Conclusão: É evidente a participação do magnésio, por meio de reações bioquímicas e metabólicas, na proteção contra esse distúrbio metabólico presente na obesidade.