Pathogenesis Of Metabolic Syndrome Research Articles

Increased Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Acute Lymphoblastic Leukemia Survivors.

Childhood cancer survivors are highly exposed to the development of side effects after many years of cessation of anticancer treatment, including altered lipid metabolism that may result in an increased risk of overweight and metabolic syndrome. Adipocyte (A-FABP) and epidermal (E-FABP) fatty acid-binding proteins are expressed in adipocytes and are assumed to play an important role in the development of lipid disturbances leading to the onset of metabolic syndrome. The aim of this study was to investigate the association between serum A-FABP and E-FABP levels, overweight, and components of the metabolic syndrome in acute lymphoblastic leukemia survivors. Sixty-two acute lymphoblastic leukemia (ALL) survivors (34 females) were included in the study. The mean age at the time of the study was 12.41 ± 4.98 years (range 4.71–23.43). Serum levels of A-FABP and E-FABP were analyzed using a commercially available ELISA kit. The ALL survivors presented statistically higher A-FABP levels in comparison with the healthy controls (25.57 ± 14.46 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with body mass index (BMI) above the normal range (18 overweight, 10 obese) had a greater level of A-FABP compared to the ALL group with normal BMI (32.02 ± 17.10 vs. 20.33 ± 9.24 ng/mL, p = 0.006). Of all participants, 53.23% had at least one risk factor of metabolic syndrome; in this group, only the A-FABP level showed a statistically significant difference compared to the healthy control group (30.63 ± 15.91 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with two or more metabolic risk factors (16.13%) presented higher levels of both A-FABP (33.62 ± 17.16 vs. 15.13 ± 7.61 ng/mL, p = 0.001) and E-FABP (13.37 ± 3.62 vs. 10.12 ± 3.21 ng/mL, p = 0.021) compared to the controls. Univariable regression models showed significant associations between BMI and systolic blood pressure with the A-FABP level (coeff. 1.02 and 13.74, respectively; p < 0.05). In contrast, the E-FABP level was only affected by BMI (coeff. 0.48; p < 0.01). The findings reported herein suggest that the increased levels of A-FABP and E-FABP may be involved in the pathogenesis of overweight and the onset of metabolic syndrome in acute lymphoblastic leukemia. However, further longitudinal, prospective studies of fatty acid-binding proteins and their potential role in the pathogenesis of obesity and metabolic syndrome in ALL survivors remain to be performed.

Association between Toxoplasma gondii infection and metabolic syndrome in obese adolescents: A possible immune-metabolic link.

Background Toxoplasmosis as a global disease is considered as a triggering factor responsible for development of several clinical diseases. However, Toxoplasma gondii (T. gondii) is an understudied parasite of potential interest in obesity research. The current study aimed to explore the role of latent T. gondii infection in the pathogenesis of metabolic syndrome (MetS) in obese adolescents through studying the relationship between serum interferon-gamma [IFN-γ] and serum chemerin in context of MetS components. Methods Eighty-three obese adolescents were serologically screened for T. gondii-IgG antibodies and compared to 35 age-matched healthy T. gondii-seronegative controls. Participants were evaluated for anthropometric measurements, total-fat mass [FM], trunk-FM, serum lipid profile, IFN-γ, and chemerin levels. Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Results The prevalence of MetS was significantly higher within obese T. gondii-seropositive group compared to obese T. gondii-seronegative group (P=0.033). Seropositive obese MetS group displayed significantly higher trunk-FM, HOMA-IR, chemerin, and IFN-γ compared to seronegative obese MetS group. Serum chemerin and IFN-γ were strongly correlated (P<0.001) and were positively correlated with BMI, WC, total-FM, trunk-FM, HOMA-IR, cholesterol, triglycerides and negatively correlated with HDLC. HOMA-IR was a common predictor for serum chemerin (P=0.030) and IFN-γ (P<0.001). Conclusions The study results suggest that T. gondii infection may exert an immune-metabolic effect that may have a potential role in the development of MetS among obese adolescents.

Olanzapine- induced metabolic syndrome pathogenesis: Hypothalamic “leptin resistance” or “pomc resistance”?

IntroductionOlanzapine (OL) represents one of the main chooses for the treatment of psychosis. However, OL increase the risk of metabolic syndrome (MS). Previous literature proposes the “Leptin resistance” as a possible hypothalamic pathogenesis of OL induced MS because of the occurrence of weight gain with increased Leptin blood level.ObjectivesThe aim of our study is to investigate in a murine model of full-MS phenotype induced by Olanzapine the hypothalamic gene expression of the pathways involved in Leptin receptor signalling to clarify if a Leptin resistance occurs.MethodsFor the experiment C57BL/6Jfemale mice are used.The OL group (n=15) received pure Olanzapine compounded into chow (54 mg/kg of diet). The vehicle group (n=15)is fed with the same chow without OL. Weight gain is measured every 5 days. After 4 weeks of treatment, mice are sacrificed by rapid cervical dislocation. Blood is collected for Glucose, Insulin and Leptin evaluation. Hypothalamus is dissected and RNA-seq is performed.ResultsThe OL group shows a significantweight gain compared to Control (p= 0.02). Likewise blood glucose, Insulin and Leptin levels appear increased (p= 0,0089, p= 0,01, p= 0,0012). From the analysis of RNA-seq hypothalamic differentially expressed genes the anorexigenic POMC pathway downstream to the Leptin Receptor shows a 4-fold increased compared to control.ConclusionsIn our study the “Leptin resistance” involvement in OL induced MS is not confirmed. In fact, although there is an increase in blood Leptin, the expression of Leptin receptor downstream pathways shows a significant increase. This could suggest a possible “POMC resistance” mechanism for OL induced MS.DisclosureNo significant relationships.

Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial.

Metabolic syndrome (MetS) pathogenesis involves oxidative stress associated with mitochondrial dysfunction, which triggers integrated stress responses via various compensatory metabolic modulators like mitokines and hepatokines. However, the regulatory mechanisms underlying the exercise-derived benefits with respect to mitokines and hepatokines (potential MetS biomarkers) are unknown. Thus, we investigated the effects of exercise training on MetS biomarkers and their associations with clinical parameters. In this single-center trial, 30 women with MetS were randomly assigned to 12-week supervised exercise or control groups (1:1) and compared with 12 age-matched healthy volunteers. All participants completed the study except one subject in the control group. Expectedly, serum levels of the mitokines, fibroblast growth factor-21 (FGF21), growth differentiation factor-15 (GDF15), and the hepatokine, angiopoietin-like 6 (ANGPTL6), were higher in MetS patients than in healthy volunteers. Moreover, their levels were markedly attenuated in the exercise group. Further, exercise-mediated changes in serum FGF21 and GDF15 correlated with changes in the homeostasis model of assessment of insulin resistance (HOMA-IR) and appendicular lean mass (ALM), respectively. Additionally, changes in serum triglycerides and ANGPTL6 were correlated with changes in leptin. Aberrant mitokine and hepatokine levels can be rectified by relieving metabolic stress burden. Therefore, exercise training may reduce the need for the compensatory upregulation of MetS metabolic modulators by improving gluco-lipid metabolism.

Hepatokines as a Molecular Transducer of Exercise.

Exercise has health benefits and prevents a range of chronic diseases caused by physiological and biological changes in the whole body. Generally, the metabolic regulation of skeletal muscle through exercise is known to have a protective effect on the pathogenesis of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and cardiovascular disease (CVD). Besides this, the importance of the liver as an endocrine organ is a hot research topic. Hepatocytes also secrete many hepatokines in response to nutritional conditions and/or physical activity. In particular, certain hepatokines play a major role in the regulation of whole-body metabolic homeostasis. In this review, we summarize the recent research findings on the exercise-mediated regulation of hepatokines, including fibroblast growth factor 21, fetuin-A, angiopoietin-like protein 4, and follistatin. These hepatokines serve as molecular transducers of the metabolic benefits of physical activity in chronic metabolic diseases, including NAFLD, T2D, and CVDs, in various tissues.

Serum Cotinine, Serum F2-isoprostane and Risk of Metabolic Syndrome in Adult Male Tobacco Users

Data on risk of metabolic syndrome among various forms of tobacco consumption in Myanmar tobacco users are currently limited. The present study aimed to determine and compare nicotine metabolites serum cotinine, oxidative stress marker serum F2-isoprostane in adult male tobacco users, and to find out relationships between these parameters and risk of metabolic syndrome. This cross-sectional study was done in 30 to 45 years old males: 84 cigarette smokers, 84 cheroot smokers and 84 betel quid with tobacco chewers. Metabolic syndrome was defined by National Cholesterol Education Program Adult Treatment Panel III definition. Serum cotinine concentration of cigarette smokers was significantly higher than that of cheroot smokers (p=0.026), however, no significant difference was seen between cigarette smokers and betel quid with tobacco chewers (p=1.000), and between cheroot smokers and betel quid with tobacco chewers (p=0.248). Serum F2-isoprostane concentration was significantly higher (p=0.001) in cigarette smokers than cheroot smokers and betel quid with tobacco chewers, but no significant difference was observed between cheroot smokers and betel quid with tobacco chewers (p=1.000). Compared with betel quid with tobacco chewers, cigarette smokers had 5.2 times (95% CI, 2.3-11.4) (p&lt;0.001) and cheroot smokers had 1.4 times (95% CI, 0.62-3.3) (p=0.402) higher risk of having metabolic syndrome. There was a significant association between the presence of metabolic syndrome and high serum cotinine as well as high serum F2-isoprostane. A significant correlation between serum cotinine and serum F2-isoprostane was found in betel quid with tobacco chewers, but not in cigarette smokers and cheroot smokers. The present study showed that both nicotine and oxidative stress take part in the pathogenesis of metabolic syndrome. Cigarette smoking has the highest risk of having metabolic syndrome, however, cheroot smoking as well as betel quid with tobacco chewing is related to metabolic syndrome as well.

Značaj određivanja C-reaktivnog proteina kod obolelih sa metaboličkim sindromom

Objecive. Previous research has shown that CRP is elevated in patients with metabolic syndrome (MS) and that low-intensity inflammation is a characteristic of MS. The aim of this study was to determine the concentration of CRP and to examine the significance of elevated CRP in MS patients. Methods. The study included 149 outpatients, 67 patients with MS (68.9 ± 8.7 years) and 82 subjects who were in the control group of the appropriate age (68.9 ± 8.6 years) (p&gt; 0.05). CRP was determined by turbidimetry and the reference range was up to 5.0 mg / L. Results. The average CRP concentration for MS patients was 5.33 ± 3.60 mg / L, while in the control group the CRP concentration value was 4.60 ± 2.03 mg / L (p &lt;0.001). There was no significant difference in CRP concentrations between men (6.02 ± 4.88 mg / L) and women with MS (4.97 ± 2.87 mg / L) (p&gt; 0.05). Almost a third of patients (29.8%) and only 6.1% of subjects in the control group had a CRP concentration greater than 5 mg / L (p &lt;0.01). Conclusion. A significantly higher frequency of elevated serum CRP concentrations in individuals with MS, compared to those without MS, indicates both the importance of inflammation in the pathogenesis of MS and CRP being biomarkers and mediators of chronic inflammation.

The association between nicotinamide N-methyltransferase gene polymorphisms and primary hypertension in Chinese Han Population

<abstract> Although no direct evidence shows that Nicotinamide N-methyltransferase (NNMT) is involved in hypertension to date, many reports have shown that NNMT plays important roles in pathogenesis of metabolic syndrome and in various cardiovascular diseases. Here we explored the genetic association between <italic>NNMT</italic> polymorphisms and primary hypertension. 308 primary hypertension cases (aged &lt; 60 years, blood pressure ≥ 140/90 mmHg or taking antihypertensive therapies) and 315 controls (aged ≥ 60 years and without any diagnosed diseases) were recruited from unrelated Chinese Han ethnicity volunteers. Then a case-control study was carried out to explore the genetic association between <italic>NNMT</italic> polymorphism and primary hypertension. A significantly associated SNP (rs1941404) was found in <italic>NNMT</italic> gene (P &lt; 0.0125). At this locus, the risks for minor homozygote CC carriers being of hypertension were highly significantly higher than those for the TT + CT carriers (OR = 2.120, OR_adjusted = 2.573, P = 0.000, P_adjusted = 0.001 and statistical power = 0.997), but the differences between the genotypes CT + CC and TT (dominant genetic model) were not statistically significant (P = 0.321, P_adjusted = 0.230 and statistical power = 0.200). In conclusion, rs1941404 in <italic>NNMT</italic> gene sequence is significantly associated with primary hypertension under a recessive inheritance mode. At this locus, the minor homozygote CC carriers are susceptible population and the TT and CT carriers are non-susceptible population. </abstract>

Evaluation of the influence of different physical and chemical composition mineral waters on the state of carbohydrate metabolism in experimental metabolic syndrome

The experiment was carried out on 68 male white rats aged 3 months, which were divided into 5 groups. Control groups: CG1 - 10 animals without exposure; CG2 - 14 animals with MS, received only drinking water. Experimental groups: EG1 - 14 rats with MS, received MW1 of chloride-sulfate sodium composition (Ivanovo region); EG2 - 15 animals, received MW2 of chloride-hydrocarbonate-sodium composition (Essentuki No. 4); EG3 - 15 animals, received MW2 enriched with selenium. MS was modeled by double injection of streptozotocin, intraperitoneally, 30 μg/kg, after 60 days of finding the animals on a hypercaloric diet. According to the oral glucose tolerance test (GTT) in animals with MS, two variants of the glycemic response were identified, according to which two subgroups (SG) were identified in each group. In the 1st SG CG2 and EG1-3, a moderate increase in glucose at the 60th minute of GTT was revealed, which was 1.2 times higher than the glucose level at the 60th minute in CG1. In SG 2, an increase in glucose was noted at the 60th minute by 2.5-5.0 times, by the 120th minute of GTG the glucose level was higher than in CG1. In animals CG2, there was no decrease in glucose by the 120th minute, in contrast to EG1-3. The activity of blood α-amylase increased by 2 times was determined in animals CG2 compared to CG1, and in groups EG1 and EG2 the level of its activity approached the level of CG1. In animals with MS, a decrease in the sensitivity of β-cells to the stimulating effect of glucose and the involvement of the exocrine pancreas in the pathological process was determined. Under the influence of therapeutic course drinking MW of different physicochemical composition in animals with MS in the experiment, the sensitivity of tissues to the stimulating hyperglycemic signal was restored to varying degrees and the increased activity of blood α-amylase decreased.

Chapter 23 - Hypothalamic microinflammation

Over the past decade, hypothalamic microinflammation has been studied and appreciated as a core mechanism involved in the advancement of metabolic syndrome and aging. Accumulating evidence suggests that atypical microinflammatory insults disturb hypothalamic regulation resulting in metabolic imbalance and aging progression, establishing a common causality for these two pathophysiologic statuses. Studies have causally linked these changes to activation of key proinflammatory pathways, especially NF-κB signaling within the hypothalamus, which leads to hypothalamic neuronal dysregulation, astrogliosis, microgliosis, and loss of adult hypothalamic neural stem/progenitor cells. While hypothalamic microinflammation is a complex, multifaceted process, initial work has been done to reveal how it contributes to the pathogenesis of metabolic syndrome and aging, and studies inhibiting hypothalamic microinflammation through targeting proinflammatory signaling pathways have shown to be beneficial against these disorders and diseases. In this chapter, we provide a broad overview on hypothalamic microinflammation, focusing on its features, inducers, and shared pathogenic roles in metabolic syndrome and aging.

Circulating Plasma Free Fatty Acids, Insulin Resistance and Metabolic Markers in Obese Women

Objectives:Elevation of free fatty acids (FFAs) in serum is an importantrisk factor for metabolic changes.Conversely, the relationship between obesity and metabolic abnormalities, and FFAsis not yet completely understood.Thus,we aimed in this study to explore the relationship and the association between insulin resistance (IR), metabolic markers and the variation inplasmaFFAs among the obese women. Methods:This study included fifty obese women aged 25–35 years and has insulin resistance (IR)in addition to fifty age-matched healthy normal weightwomen served as control group.Blood was withdrawn after twelve hours fasting;fasting blood glucose, lipidsand plasma insulinwere estimated;IR was assessedvia the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR).Fatty acids in plasma were measured by HPLC using UV detector that was set at 200 nm.Indeed, anthropometric measurements was performed . Results:Lipid profile, fasting blood sugar, insulin resistance, oleic acids (OA), linoleic acid (LA), arachidonic acid (AA) and anthropometric measurements were significantly increased in IR women compared to control. Whereas, the mean value levels of alpha-linolenicacid(ALA)was significantly decreased in IR women compare to controls. Conclusion:lower plasma levels of ALA and higher levels of AA, OA, LA were significantly associated with risk of IR and metabolic disorder markers in obese women.These results might explain the positive benefits of foods rich with poly unsaturated fatty acids (PUFA).Obesity and IR may be associated with the alterations in composition of the circulating fatty acid.These findings underscore the potential role of PUFA in the metabolic syndrome pathogenesis.

Псориаз и метаболический синдром: обзор литературы

Psoriasis is the most common chronic dermatosis and affects 1–2% of the population of developed countries. In Russia, psoriasis incidence rate has increased by 11% since 2011. Psoriasis is a chronic inflammatory and immune-mediated skin disease and it is often associated with metabolic syndrome and its components such as obesity, arterial hypertension, insulin resistance and dyslipidemia. The risk of developing metabolic syndrome in patients with psoriasis is 40% higher than in the general population. Psoriasis and metabolic syndrome share some pathogenic mechanisms such as chronic low-grade systemic inflammation and an increased level of pro-inflammatory cytokines. Systemic inflammation causes obesity, cardiovascular diseases, diabetes. These conditions increase the risk of mortality among patients. There is a link between the severity of psoriasis and metabolic syndrome and associated with severe rash, reduction of the remission and higher risk of psoriatic arthritis development. The carriers of the risk allele of FTO gene are associated with severe psoriasis, presence of psoriatic arthritis and obesity. The article presents the issues of epidemiology, etiology and pathogenesis of psoriasis and metabolic syndrome.

Psoriasis and metabolic syndrome: a review

Psoriasis is the most common chronic dermatosis and affects 1–2% of the population of developed countries. In Russia, psoriasis incidence rate has increased by 11% since 2011. Psoriasis is a chronic inflammatory and immune-mediated skin disease and it is often associated with metabolic syndrome and its components such as obesity, arterial hypertension, insulin resistance and dyslipidemia. The risk of developing metabolic syndrome in patients with psoriasis is 40% higher than in the general population. Psoriasis and metabolic syndrome share some pathogenic mechanisms such as chronic low-grade systemic inflammation and an increased level of pro-inflammatory cytokines. Systemic inflammation causes obesity, cardiovascular diseases, diabetes. These conditions increase the risk of mortality among patients. There is a link between the severity of psoriasis and metabolic syndrome and associated with severe rash, reduction of the remission and higher risk of psoriatic arthritis development. The carriers of the risk allele of FTO gene are associated with severe psoriasis, presence of psoriatic arthritis and obesity. The article presents the issues of epidemiology, etiology and pathogenesis of psoriasis and metabolic syndrome.

Микробиота кишечника и полости рта у больных артериальной гипертензией с метаболическим синдромом

Последние годы привлекает внимание роль кишечной микробиоты в патогенезе сердечно-сосудистых заболеваний (ССЗ) и метаболического синдрома (МС). Имеются данные, что метаболиты бактерий кишечника вносят вклад в развитие атеросклероза, АГ, сердечной недостаточности, ожирения и сахарного диабета, способствуют формированию нарушений в системе иммунитета. Изменения кишечного макробиотического пейзажа повышает проницаемость кишечной стенки, способствует развитию эндотоксемии, что играет определенную роль в развитии хронического воспаления в организме, способствуя развитию ожирения и других коморбидных проявлений МС. Цель - изучение особенностей микробиоты кишечника и полости рта у больных артериальной гипертензией (АГ) на фоне МС. Методика. Исследование микробиома фекалий и ротовой жидкости пациентов с АГ и МС проводили с помощью классического бактериологического анализа. Идентификация микроорганизмов осуществлялась по морфологическим, тинкториальным, культуральным и биохимическим свойствам. Результаты. При исследовании фекалий у больных АГ с МС, в сравнении с группой больных АГ, увеличивается частота встречаемости E. coli, Klebsiella spp, выделяются Bacillus spp. Streptococcus spp., Proteus spp., Neisseria spp., S. Aureus, уменьшается частота встречаемости Lactobacillus spp., Bacteroides spp. при отсутствии Bifidobacterium spp. В ротовой жидкости у больных АГ с МС обнаруживаются Clostridium spp., Lactobacillus spp., Klebsiella spp. и в небольшом количестве присутствуют Neisseria spp., Fusobacterium spp. Заключение. В толстом кишечнике у больных АГ с МС отмечается выраженный дисбактериоз с преобладанием условно-патогенных клебсиелл, энтеробактерий, протея, золотистого стафилококка. Микробиом кишечника больных АГ без МС представлен нормальной микрофлорой. В полости рта у больных АГ с МС также преобладают условно-патогенные клостридии, клебсиеллы. Микробиота больных с АГ без МС более многообразна с преобладанием нормофлоры. In recent years, the role of intestinal microbiota in the pathogenesis of cardiovascular diseases (CVD) and metabolic syndrome (MS) has attracted attention. There is evidence that intestinal bacterial metabolites contribute to development of atherosclerosis, hypertension, heart failure, obesity, diabetes, and immune disorders. Changes in the intestinal macrobiotic landscape lead to increased intestinal permeability and endotoxemia, which play a role in chronic inflammation and facilitate development of obesity and other MS comorbidities. Aim. To study features of intestinal and oral microbiota in patients with arterial hypertension (AH) associated with MS. Methods. Study materials were feces and oral fluid of patients with AH and MS where the microbiome was studied with a classical bacteriological analysis. Microorganisms were identified by their morphological, tinctorial, cultural, and biochemical properties. Results. In feces of hypertensive patients with MS as distinct from patients with hypertension, incidences of E. coli and Klebsiella spp. were increased; Bacillus spp., Streptococcus spp., Proteus spp., Neisseria spp., and S. aureus were found; incidences of Lactobacillus spp., and Bacteroides spp. were decreased; and Bifidobacterium spp were absent. In the oral fluid of patients with AH and MS, Clostridium spp., Lactobacillus spp., Klebsiella spp. and small amounts of Neisseria spp. and Fusobacterium spp. were found. Conclusion. Pronounced dysbacteriosis with predominating opportunistic Klebsiella, enterobacteria, Proteus, and Staphylococcus aureus was observed in the large intestine of hypertensive patients with MS. The intestinal microbiome of patients with AH (without MS) was represented by normal microflora. Conditionally pathogenic Clostridium and Klebsiella also predominated in the oral cavity of patients with hypertension and MS. The microbiota of patients with AH without MS was more diverse with predominating normal flora.

Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice

Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)–protein kinase A (PKA)–nuclear factor kappa-B (NF-κB) signaling pathway and ameliorates high fat diet-induced murine metabolic syndrome. Knockdown of CAP1 in macrophages abrogated the resistin-mediated inflammatory activity. In contrast, overexpression of CAP1 in macrophages aggravated inflammation. Taken together, our study identifies celastrol, which directly targets CAP1 in macrophages, might be a promising drug candidate for the treatment of inflammatory metabolic diseases, such as metabolic syndrome.

Serum insulin-like growth factor-1, asthma, and lung function among British adults

BackgroundInsulin-like growth factor-1 (IGF-1) plays a key role in the pathogenesis of metabolic syndrome, which is in turn associated with asthma. Whether IGF-1 contributes to asthma causation or asthma severity is largely unknown. ObjectiveTo evaluate the relation between serum IGF-1 and asthma, asthma outcomes, and lung function in adults. MethodsCross-sectional study of 297,590 adults (aged 40-69 years) who participated in the United Kingdom Biobank, had no diagnosis of diabetes, and were not on insulin. Multivariable logistic or linear regression was used to analyze serum IGF-1 and physician-diagnosed asthma, current wheezing, asthma hospitalizations, and lung function measures (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1 to FVC ratio). ResultsSerum IGF-1 levels above the lowest quartile (Q1) were significantly associated with lower odds of asthma (adjusted odds ratio for fourth quartile [Q4] vs Q1 = 0.88; 95% confidence interval [CI], 0.85-0.91). Among the participants with asthma, IGF-1 levels above Q1 were significantly associated with lower odds of current wheezing (adjusted odds ratio for Q4 vs Q1 = 0.89; 95% CI, 0.83-0.96), but not with asthma hospitalizations. Serum IGF-1 was significantly and positively associated with FEV1 (b = 20.9 mL; 95% CI, 19.1-22.7) and FVC (b = 25.6 mL; 95% CI, 23.4-27.7), regardless of an asthma diagnosis; these associations were significant in men and women, with larger estimated effects in men. ConclusionIn a large study of British adults, higher serum IGF-1 levels were associated with lower odds of asthma and current wheezing and higher FEV1 and FVC. Our findings suggest potential beneficial effects of circulating IGF-1 on asthma and asthma outcomes in adults.

Etiopathogenetic parallels and unresolved issues of pathogenesis of comorbidity COPD and metabolic syndrome (review)

The review analyzes the etiological and pathogenetic factors (including immunopathogenesis factors) of chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MS), cites data on clinical and pathogenetic characteristics of combined pathology, emphasizes the commonality of risk factors and individual links of pathogenesis in syntropy.The clinical and pathogenetic features of the comorbidity of COPD and MS are closely related to the severity of chronic “metabolic” inflammation induced by elements of adipose tissue. Functional and biochemical disorders recorded in metabolic syndrome (insulin resistance, hyperglycemia, dyslipidemia) are considered as factors contributing to dysfunction of the components of innate and adaptive immunity.The review formulates a number of unresolved issues of the pathogenesis of comorbid pathology, the study of which is necessary to search for the mutual aggravating effect of COPD and MS mechanisms. In view of the clinical and laboratory metabolic syndrome equivalents variety, the authors emphasize the relevance of future studies of the pathogenetic features of chronic inflammation associated with the comorbidity of the main components of metabolic syndrome and COPD, to develop effective methods of prevention and pathogenetic therapy of comorbid pathology.

Adiponectin enhances apolipoprotein a-1 gene expression in HepG2 cells: The studying of AdipoR1 and AdipoR2-dependent signaling pathways

Background and Aims: Adipose tissue hormone adiponectin is involved in pathogenesis of metabolic syndrome and atherosclerosis. Earlier it was shown that adiponectin increases the expression of apolipoprotein A-1 (apoA-1) gene in human hepatoma cells, HepG2, but signaling mechanisms of this effect remain unknown. The study is dedicated to resolving this issue.

Association Between SIRT1, Cytokines, and Metabolic Syndrome in Schizophrenia Patients With Olanzapine or Clozapine Monotherapy.

Objective: Previous studies consistently showed the interaction between Sirtuin 1 (SIRT1) and immune inflammation is significantly related to metabolic abnormalities, but their role in the pathogenesis of metabolic syndrome caused by second-generation antipsychotics (SGAs) in schizophrenia patients largely remains unknown. Hence, the present study aimed to fill this gap.Methods: A total of 54 schizophrenia patients with olanzapine or clozapine monotherapy [metabolic syndrome (MetS)/non-MetS patients, 27/27] and 67 healthy subjects were recruited in the present study. The Positive and Negative Syndrome Scale was used, and the plasma levels of SIRT1, interleukin 6 (IL-6), IL-8, IL-10, and tumor necrosis factor α (TNF-α) were measured.Results: The results showed that schizophrenia patients treated with olanzapine or clozapine (both MetS and non-MetS groups) had significantly higher plasma levels of IL-6, IL-10, and TNF-α compared to normal controls (all P < 0.05). Moreover, the MetS patients exhibited markedly lower plasma levels of SIRT1 and higher plasma levels of IL-6 than non-MetS patients and normal controls (all P < 0.05). However, there were no significant differences in IL-8 levels between groups. Our correlation analysis showed that SIRT1 was significantly correlated with diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol in schizophrenia patients. The stepwise logistic regression analysis further identified the IL-6 × SIRT1 (β = −0.463, t = 10.040, P = 0.002) as the influencing factor for the MetS in the patients.Conclusion: Our preliminary findings suggest that SIRT1 interacted with inflammatory cytokines associated with MetS in schizophrenia patients treated with SGA monotherapy.

Metabolic syndrome and pregnancy. Is there a gastroenterological trace?

In recent years, in the pathogenesis of metabolic syndrome (MS), great importance has been attached to non-alcoholic fatty liver disease (NAFLD) and violation of the intestinal microbial-tissue complex. This review summarizes current data on possible pathophysiological mechanisms that link NAFLD, pregnancy, and intestinal microbiota disorders. The clinical consequences of NAFLD influence on pregnancy and development of obstetric complications and adverse perinatal outcomes are analyzed.