Regulation of cardiovascular health and disease by visceral adipose tissue-derived metabolic hormones.

Visceral adipose tissue (VAT) is a metabolic organ known to regulate fat mass, and glucose and nutrient homeostasis. VAT is an active endocrine gland that synthesizes and secretes numerous bioactive mediators called 'adipocytokines/adipokines' into systemic circulation. These adipocytokines act on organs of metabolic importance like the liver and skeletal muscle. Multiple preclinical and in vitro studies showed strong evidence of the roles of adipocytokines in the regulation of metabolic disorders like diabetes, obesity and insulin resistance. Adipocytokines, such as adiponectin and omentin, are anti-inflammatory and have been shown to prevent atherogenesis by increasing nitric oxide (NO) production by the endothelium, suppressing endothelium-derived inflammation and decreasing foam cell formation. By inhibiting differentiation of vascular smooth muscle cells (VSMC) into osteoblasts, adiponectin and omentin prevent vascular calcification. On the other hand, adipocytokines like leptin and resistin induce inflammation and endothelial dysfunction that leads to vasoconstriction. By promoting VSMC migration and proliferation, extracellular matrix degradation and inflammatory polarization of macrophages, leptin and resistin increase the risk of atherosclerotic plaque vulnerability and rupture. Additionally, the plasma concentrations of these adipocytokines alter in ageing, rendering older humans vulnerable to cardiovascular disease. The disturbances in the normal physiological concentrations of these adipocytokines secreted by VAT under pathological conditions impede the normal functions of various organs and affect cardiovascular health. These adipokines could be used for both diagnostic and therapeutic purposes in cardiovascular disease.

Adipocytokines and disease progression in endometrial cancer: a systematic review.

The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane, Web of Science, Embase and Google Scholar was performed for English language articles from January 2000 to December 2020 using the keywords: (Endometrial cancer) AND (progression OR metastasis) AND (adipocytokine OR adiponectin OR leptin OR visfatin OR IL-6 OR TNF-α OR adipokine OR cytokine). Forty-nine studies on adipocytokines have been included in this review. Adiponectin has been linked with anti-proliferative and anti-metastatic effects on endometrial cancer cells and is associated with a better prognosis. Leptin, visfatin and resistin are linked to the stimulation of endometrial cancer growth, proliferation, invasion and metastasis and are associated with worse prognosis or with a higher grade/stage of endometrial cancer. IL-6, Il-11, IL-31, IL-33, TNF-α, TGF-ß1, SDF-1 and CXCR are involved in endometrial cancer cell growth and metastasis or involved in epithelial mesenchymal transformation (EMT) or associated with advanced disease. Adipocytokines have been found to directly impact endometrial cancer cell proliferation, invasion and migration. These molecules and their signalling pathways may be used to determine prognosis and course of the disease and may also be exploited as potential targets for cancer treatment and prevention of progression.

Adipocytokine plasma level changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women.

BACKGROUND: Adipocytokines are signaling molecules secreted by adipose tissue contributing to the control of body fat, energy expenditure and secretion of insulin and cytokines. They have been related to the development of obesity, type-2 diabetes, cardiovascular diseases and cancer. Diet and physical activity (PA) may have beneficial effects on their level. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of adipocytokines as a secondary analysis in the DAMA (Diet, physical Activity and Mammography) trial. METHODS: The 234 study participants (healthy postmenopausal women with high breast density, 50-69 years, non-smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Leptin, resistin and adiponectin were measured at baseline and at the end of the intervention. Analyses were performed using Tobit regression. RESULTS: After 24 months, women randomised to PA intervention (arms #2 + #3) showed significant lower level of leptin (37.5% lower) and resistin (65.6% lower) compared to the control group (arms #1 + #4). No significant differences emerged in adiponectin levels. No significant differences in leptin, resistin and adiponectin levels at follow-up emerged in women randomised to the dietary intervention (arms #1 + #3) in comparison with controls (arms #2 + #4). CONCLUSION: This study supports the effectiveness of PA, even at moderate intensity, in improving the leptin and resistin profile in postmenopausal women. TRIAL REGISTRATION NUMBER: ISRCTN28492718, date of trial registration 17/05/2012.

Role of adipokines (omentin and visfatin) in coronary artery disease.

AIMS: Adipose tissue is considered as an endocrine organ that releases bioactive factors known as adipokines which contribute to the pathogenesis of rotundity-linked metabolic and cardiovascular complications. Rotundity is a major predisposer for the development and progression of coronary artery disease (CAD). DATA SYNTHESIS: The literature survey from various databases such as Pubmed/Medline, DOAJ, Scopus, Clarivate analytics/Web of Science and Google Scholar were used to prepare this article. The epidemic of rotundity has gained significant attention to understand the biology of adipocytes and the metabolism of adipose tissue in obese individuals. In CAD, visfatin/NAMPT was primarily indicated as a clinical marker of atherosclerosis, endothelial dysfunction and vascular injury having a prognostic significance. Visfatin/NAMPT is a factor that promotes vascular inflammation and atherosclerosis. Omentin is an anti-inflammatory and anti-atherogenic adipokine regulating cardiovascular functions. CONCLUSIONS: This review highlights and summarizes the scientific information pertaining to the role of the adipokines - omentin and visfatin in CAD.

Adipocytokine correlates of childhood and adolescent mental health: A systematic review.

The objective of this systematic review was to determine the current state of the literature regarding how adipocytokines associate with mental health symptoms/disorders in youth. Findings summarized in this review suggested that in neurodevelopmental disorders, higher levels of leptin, ghrelin, resistin, and visfatin as well as lower levels of adiponectin, retinol-binding protein 4, and progranulin predicted increased risk for or were conflated with autism spectrum disorder. Adipocytokine correlates of attention-deficit hyperactivity disorder and related symptoms included higher apelin, higher leptin-to-adiponectin ratio, and lower adiponectin. Evidence from studies examining anxiety symptoms evinced mixed results regarding leptin, and one study suggested higher levels of ghrelin. Depressive symptoms correlated with higher leptin and ghrelin. Research examining posttraumatic stress symptoms found higher levels of ghrelin. In research examining broadband symptoms, conflicting results emerged for associations between internalizing symptoms (i.e., symptoms of emotional stress) and leptin in youth. Low levels of adiponectin and high levels of leptin predicted externalizing symptoms. Total symptom difficulties were associated with a higher leptin-to-adiponectin ratio. Our findings suggest that adipocytokines may be an important set of biomarkers to consider as underlying mechanisms contributing to developmental psychopathology.

Actinidia deliciosa Extract as a Promising Supplemental Agent for Hepatic and Renal Complication-Associated Type 2 Diabetes (In Vivo and In Silico-Based Studies).

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However, the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway. Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic acid, and melezitose as components of kiwi extract that docked well with potential as effective natural products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the treatment of diabetic hepatorenal complications.

Adipose Tissue, Non-Communicable Diseases, and Physical Exercise: An Imperfect Triangle.

The study of adipose tissue has received considerable attention due to its importance not just in maintaining body energy homeostasis but also in playing a role in a number of other physiological processes. Beyond storing energy, adipose tissue is important in endocrine, immunological, and neuromodulatory functions, secreting hormones that participate in the regulation of energy homeostasis. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favoring the secretion of deleterious adipocytokines that induce a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases and even some types of cancer. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity, with emphasis on hypocaloric diets and exercise. The aim of this review is to examine the pathophysiological mechanisms of obesity, considering the relationship among adipose tissue and two aspects that contribute positively or negatively to keeping a healthy body homeostasis, namely, exercise and noninfectious diseases. We conclude that the relationship of these aspects does not have homogeneous effects among individuals. Nevertheless, it is possible to establish some common mechanisms, like a decrease in pro-inflammatory markers in the case of exercise, and an increase in chronic inflammation in non-communicable diseases. An accurate diagnosis might consider the particular variables of a patient, namely their molecular profile and how it affects its metabolism, routines, and lifestyle; their underling health conditions; and probably even the constitution of their microbiome. We foresee that the development and accessibility of omics approaches and precision medicine will greatly improve the diagnosis, treatment, and successful outcomes for obese patients.

Effect of non-surgical periodontal treatment on cytokines/adipocytokines levels among periodontitis patients with or without obesity: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to evaluate the effects of non-surgical periodontal therapy (NSPT) on inflammatory-related cytokines/adipocytokines in periodontitis patients with or without obesity. METHODS: We followed the preferred reporting items for systematic reviews and meta-analyses statement and registered the study (CRD42022375331) in the Prospective International Register of Systematic Reviews. We screened randomized-controlled trials and controlled clinical trials from six databases up to December 2022. Quality assessment was performed with RoB-2 and ROBINS-I tools for randomized trials and non-randomized trials, respectively. Meta-analysis was carried out using a random-effect model. RESULTS: We included seventeen references in the systematic analysis, and sixteen in the meta-analysis. Baseline results of pro-inflammatory biomarkers, including serum interleukin (IL)-6, serum and gingival crevicular fluid (GCF), tumor necrosis factor (TNF)-a, serum C-reactive protein (CRP)/hs-CRP, and serum and GCF resistin, were higher in obesity subjects than in normal weight subjects. The effect of NSPT with respect to levels of cytokines/adipocytokines, including IL-6, TNF-a, CRP/hs-CRP, resistin, adiponectin, leptin and retinol binding protein 4 (RBP4), were then analyzed in the systematic and meta-analysis. After three months of NSPT, serum (MD = -0.54, CI = -0.62 - -0.46), and GCF (MD = -2.70, CI = -4.77 - -0.63) levels of IL-6, along with the serum RBP4 (MD = -0.39, CI = -0.68-0.10) decreased in periodontitis individuals with obesity. NSPT also improved GCF adiponectin levels after three months (MD = 2.37, CI = 0.29 - 4.45) in periodontitis individuals without obesity. CONCLUSIONS: Obese status altered the baseline levels of cytokines/adipocytokines (serum IL-6, serum and GCF TNF-a, serum CRP/hs-CRP, and serum and GCF resistin). Then NSPT can shift the levels of specific pro-inflammatory mediators and anti-inflammatory mediators in biological fluids, both in obesity and non-obesity individuals. NSPT can reduce serum and GCF IL-6 levels together with serum RBP4 level in individuals with obesity after 3 months, besides, there is no sufficient evidence to prove that obese patients have a statistically significant decrease in the levels of other cytokines compared to patients with normal weight. NSPT can also increase GCF adiponectin level in normal weight individuals after 3 months. Our findings imply the potential ideal follow-up intervals and sensitive biomarkers for clinical bioanalysis in personalized decision-making of effect of NSPT due to patients' BMI value.

Coronary circulatory function with increasing obesity: A complex U-turn.

AIMS: The aim of this investigation was to explore and characterize alterations in coronary circulatory function in function of increasing body weight with medically controlled cardiovascular risk factors and, thus, "metabolically" unhealthy obesity. MATERIALS AND METHODS: We prospectively enrolled 106 patients with suspected CAD but with normal stress-rest myocardial perfusion on 13 N-ammonia PET/CT and with medically controlled or no cardiovascular risk factors. 13 N-ammonia PET/CT concurrently determined myocardial blood flow (MBF) during pharmacologically induced hyperaemia and at rest. Based on body mass index (BMI), patients were grouped into normal weight (BMI: 20.0-24.9 kg/m2 , n = 22), overweight (BMI: 25.0-29.9 kg/m2 , n = 27), obese (BMI: 30.0-39.9 kg/m2 , n = 31), and morbidly obese (BMI ≥ 40kg/m2 , n = 26). RESULTS: Resting MBF was comparable among groups (1.09 ± 0.18 vs. 1.00 ± 0.15 vs. 0.96 ± 0.18 vs.. 1.06 ± 0.31 ml/g/min; p = .279 by ANOVA). Compared to normal weight individuals, the hyperaemic MBF progressively decreased in in overweight and obese groups, respectively (2.54 ± 0.48 vs. 2.02 ± 0.27 and 1.75 ± 0.39 ml/g/min; p < .0001), while it increased again in the group of morbidly obese individuals comparable to normal weight (2.44 ± 0.41 vs. 2.54 ± 0.48 ml/g/min, p = .192). The BMI of the study population correlated with the hyperaemic MBF in a quadratic or U-turn fashion (r = .34, SEE = 0.46; p ≤ .002). CONCLUSIONS: The U-turn of hyperaemic MBF from obesity to morbid obesity is likely to reflect contrasting effects of abdominal versus subcutaneous adipose tissue on coronary circulatory function indicative of two different disease entities, but needing further investigations.

The addition of different oils in the diet regulates the expression of adipocytokine signaling genes in sheep longissimus dorsi muscle.

Nutrition is an important factor that regulates the expression of several genes. The aim of this work was to analyze the effects of diets containing additions of different oils on the regulation of the adipocytokine signaling gene expressions in sheep longissimus dorsi muscle. Forty males and non-neutered sheep were kept in individual cages and fed under four different treatments: control treatment (concentrate and forage) and the other three treatments containing the concentrate and forage plus 4% oil (yellow grease, soybean and palm oils). After slaughter, samples of the longissimus dorsi muscle were collected. RNA extraction followed by Real Time PCR for five adipocytokine signaling genes. ANOVA was performed followed by the Dunnett's test (0.01). The normalized expressions of the ACLY gene were not significant between treatments to control, but for the ALDOC gene, all oil-supplemented treatments were significantly downregulated relative to the control treatment. The DUSP gene was not significantly expressed between the oil-supplemented treatments to control treatment. The ENPP1 gene was significantly upregulated with the addition of palm oil and yellow grease and the FASN gene was only significantly expressed in soybean oil-supplemented treatment to control treatment. It was concluded that the addition of different oils in the sheep diet regulated the expression of most genes for up or down, which can influence the metabolic pathways responsible for the fatty acid biosynthesis in the sheep longissimus dorsi muscle.

The follicular fluid adipocytokine milieu could serve as a prediction tool for fertility treatment outcomes.

RESEARCH QUESTION: Can the adipocytokine milieu of the follicular niche improve the ability to predict treatment outcomes in infertile patients? DESIGN: Follicular fluid samples from overweight patients were analysed and compared with samples from matched normal-weight patients. Concentrations of adiponectin, chemerin, C-reactive protein, interleukin-6 (IL-6), IL-10, IL-18, insulin, leptin, prolactin, resistin, tumour necrosis factor alpha (TNF-α) and bone morphogenetic protein-15 (BMP-15) were assessed by multiple magnetic bead immunoassay (MMBI) and enzyme-linked immunosorbent assay and correlated with fertility treatment outcomes. RESULTS: Analysis of samples from 22 overweight and 22 normal-weight patients demonstrated that TNF-α can predict oocyte maturation rate. When stratified by body mass index (BMI), IL-10 emerges as a better predictor of oocyte maturation in normal-weight patients. Prolactin was a negative predictor for fertilization rate in the full cohort, and this prediction power was lost upon stratification. No adipocytokines were predictive of blastulation rate, and only age remained predictive. BMP-15 was a strong predictor of high-quality blastulation in the full cohort, more so in the normal-weight population. CONCLUSIONS: The adipocytokine milieu of the follicular fluid provides a snapshot of the growing oocyte's environment and can help predict fertility treatment outcomes, fine-tuning understanding of the dysregulation caused by increasing BMI. Inflammatory cytokines can predict oocyte maturation; prolactin, oocyte competence; and BMP-15, high-quality blastulation. Further analysis of these findings with a larger sample size and assessing individual oocytes will help shed more light on the clinical significance of these findings.

Association of adipocytokines serum levels with left atrial thrombus formation in atrial fibrillation patients on oral anticoagulation (Alert) - A cross-sectional study.

BACKGROUND AND AIMS: Oral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events. METHODS AND RESULTS: In this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (loge) leptin (G1: 2.0 ± 1.3 µg/ml, G2: 2.0 ± 1.1 µg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association. CONCLUSIONS: Our results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.

The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections.

Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data.

Adipocytokines: Are they the Theory of Everything?

INTRODUCTION: Adipose tissue secretes various bioactive peptides/proteins, immune molecules and inflammatory mediators which are known as adipokines or adipocytokines. Adipokines play important roles in the maintenance of energy homeostasis, appetite, glucose and lipid metabolism, insulin sensitivity, angiogenesis, immunity and inflammation. Enormous number of studies from all over the world proved that adipocytokines are involved in the pathogenesis of diseases affecting nearly all body systems, which raises the question whether we can always blame adipocytokines as the triggering factor of every disease that may hit the body. OBJECTIVE: Our review targeted the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems including diabetes mellitus, kidney diseases, gynecological diseases, rheumatologic disorders, cancers, Alzheimer's, depression, muscle disorders, liver diseases, cardiovascular and lung diseases. METHODOLOGY: We cited more than 33 recent literature reviews that discussed the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems. CONCLUSION: More evidence is being discovered to date about the role played by adipocytokines in more diseases and extra research is needed to explore hidden roles played by adipokine imbalance on disease pathogenesis.

Adipocytokines are not associated with gestational diabetes mellitus but with pregnancy status.

AIMS: Adipose tissue-secreted proteins, i.e. adipocytokines, have been identified as potential mediators linking fat mass and adipose tissue dysfunction with impaired glucose homeostasis, alterations in the inflammatory status, and risk of diabetes. The aim of this study was to determine whether seven circulating adipocytokines are associated with gestational diabetes mellitus (GDM) or are altered by metabolic and weight changes during pregnancy itself. METHODS: A panel of seven adipocytokines (i.e. adiponectin, adipocyte fatty acid-binding protein, chemerin, leptin, Pro-Enkephalin, progranulin, and Pro-Neurotensin) was quantified in serum in a cross-sectional cohort of 222 women with the following three groups matched for age and body mass index: (i) 74 pregnant women with GDM; (ii) 74 pregnant women without GDM; and (iii) 74 non-pregnant and healthy women. A stepwise statistical approach was used by performing pairwise comparisons, principal component analysis (PCA), and partial least square discriminant analysis (PLS-DA). RESULTS: Five out of seven adipocytokines were dysregulated between pregnant and non-pregnant women, i.e. adiponectin, chemerin, leptin, Pro-Enkephalin, and progranulin. None of the adipocytokines significantly differed between GDM and non-GDM status during pregnancy. The same five adipocytokines clustered in a principal component representing pregnancy-induced effects. Fasting insulin was the most relevant parameter in the discrimination of GDM as compared to pregnant women without GDM, whereas chemerin and adiponectin were most relevant factors to discriminate pregnancy status. CONCLUSIONS: Pregnancy status but not presence of GDM can be distinguished by the seven investigated adipocytokines in discrimination analyses.

Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors.

BACKGROUND: Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. METHODS: A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). RESULTS: Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (ß = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (ß = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). CONCLUSIONS: Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Obesity worsens central inflammation and disability in multiple sclerosis.

BACKGROUND: Previous studies evidenced a link between metabolic dysregulation, inflammation, and neurodegeneration in multiple sclerosis (MS). OBJECTIVES: To explore whether increased adipocyte mass expressed as body mass index (BMI) and increased serum lipids influence cerebrospinal fluid (CSF) inflammation and disease severity. METHODS: In this cross-sectional study, 140 consecutive relapsing-remitting (RR)-MS patients underwent clinical assessment, BMI evaluation, magnetic resonance imaging scan, and blood and CSF collection before any specific drug treatment. The CSF levels of the following cytokines, adipocytokines, and inflammatory factors were measured: interleukin (IL)-6, IL-13, granulocyte macrophage colony-stimulating factor, leptin, ghrelin, osteoprotegerin, osteopontin, plasminogen activator inhibitor-1, resistin, and Annexin A1. Serum levels of triglycerides, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were assessed. RESULTS: A positive correlation emerged between BMI and Expanded Disability Status Scale score. Obese RR-MS patients showed higher clinical disability, increased CSF levels of the proinflammatory molecules IL-6 and leptin, and reduced concentrations of the anti-inflammatory cytokine IL-13. Moreover, both the serum levels of triglycerides and TC/HDL-C ratio showed a positive correlation with IL-6 CSF concentrations. CONCLUSION: Obesity and altered lipid profile are associated with exacerbated central inflammation and higher clinical disability in RR-MS at the time of diagnosis. Increased adipocytokines and lipids can mediate the negative impact of high adiposity on RR-MS course.

Adipocytokines and their relationship to endometrial cancer risk: A systematic review and meta-analysis.

OBJECTIVE: To investigate the association between circulating levels of adipocytokines (adiponectin, leptin, tumour necrosis factor alpha (TNFα), interleukin 6 (IL-6)) and growth factors (insulin-like growth factor I (IGF-I) and II (IGF-II)), and the risk of endometrial cancer. METHODS: Cochrane, CINAHL, Embase, Medline and Web of Science were searched for English-language manuscripts published between January 2000 and August 2018 using the following string of words: cancer and endometrial and (obesity or BMI) and (adiponectin or TNF* or IGF-I or IGF-II or IL-6 or leptin). RESULTS: Twenty articles were included in this meta-analysis, which corresponded to 18 studies involving 2921 endometrial carcinoma cases and 5302 controls. Fourteen articles reported circulating levels for adiponectin, seven for leptin, three for TNFα, three for IL-6 and one for IGF-I. No article reported values for IGF-II. Patients with circulating adiponectin levels in the highest tertile had decreased endometrial cancer risk compared to women with levels in the lowest tertile, (summary of odds ratio (SOR) 0.51, 95% confidence interval (CI): 0.38-0.69, p < 0.00001). Women with circulating leptin concentrations in the highest tertile had increased endometrial cancer risk compared to women with concentrations in the lowest tertile (SOR 2.19, 95% CI: 1.45-3.30, p = 0.0002). There was no difference in cancer risk between participants with the highest TNFα and IL-6 levels compared to the lowest levels (SOR 1.27, 95% CI: 0.88-1.83, p = 0.20 and SOR 1.20, 95% CI: 0.89-1.63, p = 0.23, respectively). CONCLUSIONS: Endometrial cancer risk is inversely affected by adiponectin and leptin levels. There appears to be no relationship between TNFα and IL-6 and the overall risk of endometrial cancer.

The Effect of Noninvasive Bariatric Surgery on the Levels of Certain Adipokines and Atherosclerosis Risk Factors in Patients with Metabolic Syndrome.

Objective: Besides glucose intolerance, dyslipidemia, and hypertension, visceral obesity is one of the most important atherogenic pathological factors in patients with metabolic syndrome (MetS). The aim of this study is to examine whether weight loss following BioEnterics Intragastric Balloon (BIB-system) therapy affects adipokine concentration and atherosclerosis risk factor profile in patients with MetS.Methods: The study group comprised 30 patients (17 female, BMI = 38.5 ± 8.6 kg/m2; 13 male, BMI = 43.3 ± 7 kg/m2) with MetS qualified to BIB-system therapy. The control group included 18 age matched healthy volunteers (10 female, BMI = 23.3 ± 2.8 kg/m2 and eight male, BMI = 27.3 ± 0.9 kg/m2). Biochemical analyses of blood samples and anthropometric measurements were conducted, before and after six-month BIB system therapy.Results: BIB therapy resulted in a significant drop in body weight, and body fat percentage, and in BMI, VAI, WHtR, BAI, TG, glucose, hsCRP, and leptin levels. In addition Tc/HDL, LDL/HDL, TG/HDL, and leptin/adiponectin ratios fell significantly, and adiponectin concentration increased. All anthropometric parameters apart from Tc and hsCRP, were significantly different post-therapy compared to healthy controls. The therapy induced downregulation of hsCRP which was positively correlated with the reduction in body weight, BMI and BAI. The decrease in leptin concentration correlated positively with the fall in total cholesterol and body weight. The fall in leptin/adiponectin ratio positively correlated with the downregulation of BAI and body fat.Conclusion: BIB therapy appears to have beneficial effects on MetS. This is indicated by amelioration of the pro-inflammatory status related to obesity, demonstrated by an improved lipid profile significant downregulation of hsCRP concentration following therapy.

Impact of malnutrition on systemic immune and metabolic profiles in type 2 diabetes.

BACKGROUND: While obesity and overweight status are firmly established risk factors for Type 2 diabetes mellitus (T2DM), a substantial proportion of diabetic individuals, especially in Africa and Asia, are often underweight or normal weight. However, very little is known about the immunological and metabolic profiles of these individuals. METHODS: This study aimed to assess the relationship between malnutrition and Type 2 diabetes mellitus (T2DM). We examined a variety of analytes associated with the immunological and metabolic profiles of T2DM individuals with low (< 18.5 kg/m2) or normal (18.5-24.9 kg/m2) body mass index (BMI). To this end, we measured plasma levels of HbA1c, glucose, insulin, glucagon, adipocytokines and Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in T2DM individuals with low BMI (LBMI) or normal BMI (NBMI) with small sample size n = 44 in each group. RESULTS: LBMI individuals exhibited significantly higher levels of HbA1c, random blood glucose, insulin and glucagon compared to NBMI individuals. Similarly, LBMI individuals exhibited significantly higher levels of adiponectin and adipsin and significantly lower levels of leptin in comparison to NBMI individuals. LBMI individuals also exhibited significantly lower levels of the Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in comparison to NBMI individuals. Finally, while the metabolic parameters exhibited a significant negative correlation with BMI, the immunological parameters exhibited a significant positive correlation with BMI. CONCLUSIONS: Malnutrition is associated with a significant modulation of glycemic, hormonal and cytokine parameters in T2DM. Hence, the biochemical and immunological profiles of T2DM is significantly influenced by BMI.