Adipose Tissue-derived Hormone Research Articles

Relationships between Body Composition and Plasma Levels of Pancreatic, Gut, and Adipose Tissue Hormones in db/db Mice, a Model of Type 2 Diabetes Mellitus.

We studied the relationships between body composition parameters and plasma levels of pancreatic, gut, and adipose tissue hormones regulating energy balance and glucose metabolism in diabetic db/db mice (BKS.Cg-Dock7m+/+Leprdb/J). The body composition parameters in mice aged 8, 12, and 16 weeks were assessed by magnetic resonance imaging. The concentrations of insulin, glucagon, ghrelin, glucagon-like peptide-1, glucose-dependent immunotropic peptide, leptin, resistin, and plasminogen activator-1 were measured by multiplex analysis at the age of 8 and 16 weeks. In comparison with non-diabetic control (db/+), db/db mice demonstrated high fat mass and reduced lean body mass and water content. In 8- and 16-week-old db/db mice, the levels of leptin (p<0.001), insulin (p<0.01), and glucagon-like peptide-1 (p<0.05) were elevated and the concentration of ghrelin (p<0.05) was reduced. The body weight and fat mass positively correlated with the levels of leptin, insulin, plasminogen activator-1, and glucagon-like peptide-1 and negatively correlated with ghrelin concentration. The results provide further details for characteristics of db/db mice, a widely used model of obesity and type 2 diabetes mellitus.

THE ROLE OF APELIN AND VISFATIN IN PATIENTS WITH ATRIAL FIBRILLATION

Objective: Adipokines such as apelin and visfatin represent two adipose tissue hormones that have been linked to cardiovascular diseases. Apelin has a positive inotropic effect and contributes to regulation of blood pressure, arterial vasodilation and improvement of cardiac output. Conversely, visfatin is associated with endothelial dysfunction, angiogenesis and atherosclerotic plaque instability. However, the exact impact of these biological factors in the presence of atrial fibrillation (AF) remains unclear.Design and method: Overall, 100 patients (50 with AF and 50 without AF) matched for age, gender and body mass index were studied. Apelin and visfatin plasma levels were measured by the Elisa method. Results: Apelin plasma levels were significantly lower whereas visfatin levels were significantly higher in patients with AF compared to controls. Conclusions: Reduced apelin and increased visfatin levels were observed in patients with AF indicating a potential role as independent prognostic factors for this condition.

Immunohistochemical analysis of adiponectin in atherosclerotic lesions of human aorta.

BACKGROUNDMetabolic syndrome, a cluster of interrelated disorders including abdominal obesity, insulin resistance, dyslipidemia, and hypertension (HTN) plays an important role in development of atherosclerotic lesions in arterial wall. Dysregulation of adipose tissue hormones (adipokines) production is a possible link between abdominal obesity and other manifestations of metabolic syndrome. Adiponectin is a well-known adipokine which affects metabolism and inflammatory response. However, data on its role in atherogenesis are still controversial. The aim of this study is to investigate whether adiponectin is present in atherosclerotic lesions of human aorta.METHODSThirty-five autopsy segments from abdominal, thoracic aortas, and aortic arch of four men (mean age: 57 years) were fixed and stained for lipids [Oil Red O (ORO)], cells [hematoxylin-eosin (H&E)], and adiponectin [indirect immunoperoxidase assay (IPA) method]. Samples of both stable and unstable plaques were selected for analysis. Human adipose tissue, THP-1 monocytes/macrophages, and human endothelial hybrid cell line (EA.hy926) were chosen for detection of adiponectin messenger ribonucleic acid (mRNA) using reverse transcription polymerase chain reaction (RT-PCR).RESULTSAdiponectin accumulations were found inside endothelial cells covering both stable and unstable atherosclerotic plaques. Focal depositions of adiponectin were also found in fibrous caps of stable lesions and atheromatous core of both stable and unstable plaques and also in adventitia. RT-PCR revealed mRNA expression of adiponectin gene in adipose tissue, but not in mononuclears and endothelial cells.CONCLUSIONAdiponectin is present in aortic plaques of humans, but is not synthesized in endothelial cells and mononuclears, at least in culture conditions. Detection of adiponectin in atherosclerotic lesions can serve as indirect evidence of possible participation of this adipokine in atherogenesis.

Coexistence of obstructive sleep apnea and telomerase activity, concentration of selected adipose tissue hormones and vascular endothelial function in patients with arterial hypertension.

The aim of the present study was to determine the effect of obstructive sleep apnea (OSA) with hypertension on telomerase activity, visfatin and adipsine concentration in the blood and vascular endothelial function assessed by ultrasound measured flow-mediated dilatation of the brachial artery (FMD). The study involved a group of 106 people (average age: 54.79 years). The determination of telomerase activity and blood visfatin and adipsine concentrations, brachial artery ultrasound examination with endothelium-dependent dilatation evaluation (FMD) and polysomnography were carried out. Patients with hypertension without OSA were characterized by significantly greater FMD in comparison to patients with arterial hypertension and OSA (8.13 ± 5.12 %vs. 6.82 ± 5.36%; p < 0.05). Negative linear relationship between apnea-hypopnea index (AHI) and FMD (r = -0.22, p < 0.05) has been demonstrated. Negative linear relationship between adipsine concentration in the blood and length of REM (Rapid Eye Movement) sleep (r = -0.21, p < 0.05) was found. Positive linear relationship between the concentration of visfatin in the blood and the length of REM sleep (r = 0.22, p < 0.05) was also observed. Higher body mass index, higher total cholesterol, triglyceride and glucose levels have been shown to be independent predictors of higher AHI values, while greater telomerase activity, greater FMD and use of angiotensin converting enzyme inhibitors are independent predicators for lower AHI values. Higher values of AHI index in polysomnography in hypertensive patients can be related to lower telomerase activity in the blood and impaired function of vascular endothelial function assessed using ultrasound.

The influence of adipose tissue hormones on the turnover of extracellular matrix components of cartilage tissue in the course of juvenile idiopathic arthritis

The influence of adipose tissue hormones on the turnover of extracellular matrix components of cartilage tissue in the course of juvenile idiopathic arthritis

Role of Glucagon-Like Peptide-1 in Appetite Regulation in Patients with Morbid Obesity and Leptin Resistance

To contribute to the outstanding discussion of suggested reasons of obesity, including the hormonal disorders, and how to deal and avoid them, this research attempts to investigate and control the energy balance disturbances resulting from hormonal disorders that may cause obesity by dysregulating appetite. A total of 88 participants are recruited, among whom 50 and 38 were allocated to the control and patients groups, respectively. Venous blood samples are collected from the participants at different time points for the quantification of the pre-prandial and 2, 6 and 12 h postprandial levels of lipid markers, including total cholesterol, high density lipoproteins, low density lipoproteins, very low density lipoproteins, and triacylglycerol, and the appetite-related hormones leptin and intestinal hormones glucagon-like peptide (GLP-1). In healthy controls, leptin levels increased prior to eating, decreased after eating, and then increased to induce hunger at several hours after eating. By contrast, the pre-prandial and postprandial leptin levels of the patients group did not show statistically significant differences. Healthy controls had moderate GLP-1 levels, whereas patients with obesity and leptin resistance had high GLP-1 levels. The GLP-1 was found to be secreted in response to high postprandial energy levels as an adaptation to leptin resistance. This study elucidates the relationship between the adipose tissue hormone leptin and GLP-1 in patients with morbid obesity. Findings of using GLP-1 as an appetite regulator for the morbidly obese patients and have leptin resistance (resistance to its action in appetite regulation), presented here, should provide a valuable information for further experimental investigations.

Effect of prenatal zinc supplementation on adipose tissue-derived hormones and neonatal weight, height and head circumference in women with impaired glucose tolerance test: randomized clinical controlled trial

Background It is well known that normal pregnancy exposes mothers to a diabetogenic state. The important role of adipose tissue in the regulation of insulin resistance has been repeatedly proven. This organ carries out the regulation of insulin resistance by producing adipocytokines involved in the pathogenesis of gestational diabetes mellitus (GDM). The present study aims to evaluate the effects of zinc supplementation on serum leptin, visfatin, tumor necrosis factor-α (TNF-α), adiponectin and zinc-α2-glycoprotein (ZAG) levels in pregnant women with impaired glucose tolerance test (IGTT) results.

Study of serum leptin levels in patients with chronic kidney disease

Background and objectives: Chronic kidney disease is a global threat to health in general and for developing countries. It is characterized by progressive deterioration of kidney function which develops eventually into a terminal stage of chronic kidney failure. Leptin is an adipose tissue-derived hormone shown to be related to several metabolic, inflammatory, and hemostatic factors related to chronic kidney disease. The objective of the study is to understand the role of serum Leptin in chronic kidney disease. Material and Methods: A case control study was done with 87 patients divided into 2 groups. 43 healthy individuals were served as controls and 44 chronic kidney disease patients were served as cases. Serum Leptin was estimated by ELISA method. Blood urea was estimated by urease method and serum creatinine by modified Jaffe‟s method. BMI was calculated. Data was analysed by using graph pad prism 7.0. Results: In the present study, patients with chronic kidney disease had significant higher levels of serum Leptin (55.88 ± 31.59),blood urea (75.23 ± 30.91), serum creatinine is (4.09 ± 1.90) and BMI is (24.66 ± 2.667) when compared to healthy individuals serum Leptin levels is (7.91 ± 8.24), blood urea (27.53 ± 8.03), serum creatinine is (1.28 ± and BMI is (23.33 ± 2.45) with a p value < 0.001. Conclusion: Serum Leptin levels were high in patients with chronic kidney disease when compared to healthy individuals even the BMI was in normal range in both patients and healthy individuals. The study concludes that serum Leptin is associated with chronic kidney disease and can be used as a marker for diagnosis and prognosis in chronic kidney disease.

Obesity, endocrine disruption and male infertility

Obesity has become a global pandemic since the last few decades with prevalence in more than one-third of the population in the United States. Another concurrent global health concern is the declining trend in male fecundity in terms of semen quality. Male infertility etiology is multifactorial with obesity serving as one of the major causatives. An array of research is directed in unveiling the potential mechanism underlying the obesity-induced male subfertility or infertility. Obesity may alter the hormonal milieu of the hypothalamic- pituitary-gonadal axis, its crosstalks with other metabolic hormones, upregulates secretion of adipose tissue-derived hormones and other factors, thus influencing the endocrine regulation of male reproduction. Obesity may also directly impair testicular functions by inducing genetic and epigenetic alterations in spermatozoa, disrupting sperm morphology and functions. Given the complexity of the condition of obesity and the multivariate etiopathology of male subfertility/ infertility, this review is aimed to provide an updated concept on how obesity mediated hormonal modulation may affect male fertility parameters.

The role of system inflammation in bronchial asthma and obesity

The prevalence of bronchial asthma and obesity has grown in the recent decades worldwide. The urgency of this problem due to its medical and social significance for the society in connection with a reduction of patients ‘ quality of life and considerable economic damage to the health system. The relationship of these diseases, there are gender-related, age-related characteristics no doubt. Growing clinical-epidemiological evidence indicates that obesity might be an independent risk factor for bronchial asthma. On the other hand, the clinical data of bronchial asthma is a consequence of obesity remain indicative. The presence of concomitant obesity, bronchial asthma is considered as a state, significantly worsens its course. Etiology the causal relationship between obesity and asthma, despite the proposed mechanical, immunological, genetic and hormonal concepts still remains unclear. The underlying mechanism for this association is still unclear although several theories have been postulated in an attempt to describe it. Many studies demonstrate that bronchial asthma and obesity have some common mechanisms, including chronic systemic inflammation. In the review, we outline the current understanding of the role of systemic inflammation linked to obesity in the pathophysiology of bronchial asthma. An important role in the pathophysiology of systemic inflammation is given to changing levels of key adipose tissue hormones - leptin and adiponectin, respectively, having proinflammatory and anti-inflammatory activity. '/'his review article will focus on the leptin and adiponectin. Understanding the mechanisms of correlation between the metabolic activity of adipose tissue and the functional status of the respiratory tract with the development of systemic inflammation with comorbid asthma and obesity will review a number of existing provisions for the diagnosis and treatment of associated course of these diseases, to expand understanding the phenotypes of asthma and to develop new treatment strategies.

The role of systemic inflammation in the pathogenesis of insulin resistance and metabolic syndrome in patients with chronic hepatitis C

The systemic inflammatory response plays a key role in the development of atherosclerosis, insulin resistance (IR) and diabetes mellitus 2-type (diabetes mellitus). IR in patients with chronic hepatitis C (CHC) is considered as a possible factor in the progression of fibrosis, a predictor of the development of DM T2 and a component of the metabolic syndrome. The use of biomarkers of non-specific inflammation can be a valuable tool for assessing the risks of IR and cardiovascular diseases in patients with chronic hepatitis C. Aim of the study. To determine the role of nonspecific inflammation in the formation of IR and metabolic syndrome in patients with chronic hepatitis C. Materials and methods. The study included 205 patients with CHC aged 18 to 69 years. Patients with CHC are randomized into two groups depending on the presence of IR: group 1 - patients with a HOMA index ≥2.77, which corresponded to IR (n=110); group 2 (n=95). The levels of serum iron, C-reactive protein (CRP), serum ferritin and adipose tissue hormones [leptin, resistin, adiponectin and tumor necrosis factor-α (TNF-α)] were additionally investigated. Results. At all stages of development of IR, nonspecific inflammation was detected (according to ferritin, CRP and serum iron), increasing with increasing HOMA index [Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)] (Matthews D., 1985), metabolic syndrome and its components. In the analysis of indicators in patients with chronic hepatitis C with a body mass index

Plasma Asprosin Levels Are Associated with Glucose Metabolism, Lipid, and Sex Hormone Profiles in Females with Metabolic-Related Diseases.

Asprosin is a white adipose tissue-derived hormone that increases abnormally in mammals with insulin resistance. However, the role of asprosin in polycystic ovary syndrome (PCOS), a disease partly characterized by insulin resistance, and its potential connection with type 2 diabetes mellitus (T2DM) and PCOS has not been thoroughly elucidated to date. To investigate the association of asprosin with metabolic profiles, sex-related hormones, or inflammation in females with T2DM or PCOS, plasma asprosin and metabolic indicators were measured in 66 healthy females, 53 female patients with T2DM, and 41 patients with PCOS. Spearman's correlation analysis and binary logistic regression analysis models were used. Plasma asprosin was significantly higher in T2DM females than in healthy subjects (P < 0.001) and was positively correlated with fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and HOMA-IR (P < 0.05). Asprosin in PCOS subjects was also higher than in healthy subjects (P < 0.001) but lower than in T2DM subjects (P < 0.05), and it was positively correlated with FBG, HbA1c, HOMA-IR, LDL-c, APOB, APOE, and testosterone (P < 0.05). The BMI-categorized subgroups of PCOS subjects also showed correlations of asprosin with metabolic profiles and sex-related hormones. Binary logistic regression analysis revealed that plasma asprosin level acted as an independent risk factor for T2DM or PCOS. These findings suggest the correlation of plasma asprosin level with glucose metabolism, lipid metabolism, sex-related hormones, and inflammation in females, supporting asprosin as a potential predictive factor for females with metabolic-related diseases. This trial is registered with ChiCTR-ROC-17010719.

Leptin stimulates the release of pro-inflammatory cytokines in hypothalamic astrocyte cultures from adult and aged rats.

Leptin is an adipose tissue-derived hormone that acts on the hypothalamus in order to maintain energy homeostasis. However, leptin can also induce an inflammatory response. Increasing evidence has highlighted a critical role of astrocytes in the effects of leptin on the hypothalamus. In addition, astrocytes participate in neuroinflammation by producing and releasing a wide range of inflammatory mediators. In this study, we aimed to investigate the age-dependent effect of leptin on pro- and anti-inflammatory cytokines released by the hypothalamic astrocyte cultures obtained from newborn, adult, and aged Wistar rats. In hypothalamic astrocytes from newborn rats, leptin did not change the release of pro-inflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). On the other contrary, leptin increased the release of both TNF-α and IL-1β in astrocyte cultures from adult and aged animals. Regarding the anti-inflammatory cytokine interleukin 10 (IL-10), we did not observe any change in response to leptin. In conclusion, our data suggests a pro-inflammatory action of leptin on the hypothalamus during aging. This in turn may be related to the triggering of metabolic disorders, as both of these conditions are associated with neuroinflammation.

Responses of Muscle Mitochondrial Function to Physical Activity: A Literature Review

Skeletal muscles play an active role in regulating the metabolic homeostasis through their ability for relating to adipose tissue and endocrine hormones. Contraction of the skeletal muscle leads to increased release of several myokines, such as irisin, which is able to interact with the adipose tissue. Physical activity promotes the irisin mechanism by augmenting the peroxisomes (PGC1-α) in the skeletal muscle. Afterwards, an elevation occurs in the membrane protein of fibronectin type III domain-containing protein 5 (FNDC5) in muscle, ultimately resulting in production of irisin. The expression of irisin and FNDC5 converts white adipose into the brown type and increases energy consumption by the whole body hindering obesity and diabetes. The effects of regular exercise training on preventing obesity, diabetes, and the related complications, as well as improving health have already been proven. However, the point is that these beneficial effects are due to the cellular-molecular mechanisms, which are still under discussion. In this review, we searched the online databases, including scientific information database (SID), Google Scholar, PubMed, Science Direct, and Scopus. The following keywords were used: training, physical activity, myokine, adipose tissue, PRDM16, PGC-1α, PPARγ, SIRT1, FGF21, bone morphogenetic protein, neurugolin, VEGF, and IL-15. All the articles, including research studies, review articles, descriptive and analytical studies, in addition to cross-sectional researches published during 1998-2017 were reviewed. According to the obtained results, it seems that expression of irisin and FNDC5 converts the white adipose into brown adipose resulting in increased energy consumption. It has been proven in the literature that regular exercise training prevents obesity, diabetes, and the related complications, as well as improving health.

Abstract 4919: Preclinical activity of SDX-7320 in mouse models of obesity and obesity-driven cancer

Abstract Cancer patients who are obese face a greater risk of dying from cancer compared to nonobese patients (Calle, 2003). Obesity is believed to contribute to metastasis and progression of cancer via multiple mechanisms: increased secretion of the adipose tissue hormone leptin, decreased secretion of adiponectin, increased production of estrogen in adipose tissue, and elevated insulin (secondary to peripheral insulin resistance) as well as the local effects of inflammatory cytokines (Gucalp, 2016). Small-molecule inhibitors of methionine aminopeptidase type 2 (MetAP2) have previously demonstrated clinical activity in oncology (Kudelka, 1998) as well as obesity/type 2 diabetes (Hughes, 2013; Kim, 2015). However, development of some small-molecule MetAP2 inhibitors has been hampered by CNS side effects (Bhargava, 1999). SDX-7320 is a copolymer-drug conjugate of a novel fumagillin-derived MetAP2 inhibitor (SDX-7539) attached via a cleavable linker to a hydroxypropylmethacrylamide (HPMA) backbone, intended to limit CNS penetration and therefore reduce CNS toxicity. In vitro MetAP2 binding assays showed that SDX-7320 was unable to bind to MetAP2 while SDX-7539 was a potent binder (apparent IC50 = 0.13 nM), indicating that cleavage of SDX-7320 is required for biologic activity. SDX-7539 inhibited proliferation of human umbilical vein endothelial cells (HUVECs) with an apparent IC50 = 0.2 nM. The preclinical efficacy of SDX-7320 was evaluated in mouse models of obesity/insulin resistance and also in syngeneic tumor models coupled with high fat diet-induced obesity (DIO)/metabolic dysfunction. Obesity and insulin resistance were induced in C57Bl/6 mice by feeding them a high-fat diet (HFD) for at least 12 weeks. SDX-7320 was dosed subcutaneously every 4 days (for 28 days) into DIO mice or control mice fed a low-fat diet. SDX-7320 caused significant reduction in body weight and fat mass in obese mice while also reversing insulin resistance relative to controls. In addition, SDX-7320 caused greater reduction in body weight in obese mice relative to lean mice. Circulating levels of leptin and insulin were reduced while levels of adiponectin were increased in response to SDX-7320. In mouse models of obesity-accelerated tumor growth, SDX-7320 was more efficacious in obese relative to lean mice harboring subcutaneous B16F10 melanoma or EO771 mammary gland tumors. These effects occurred without any signs of neurotoxicity. SDX-7320, currently in phase I (solid tumors; all-comers; NCT02743637), is being developed for the treatment of cancers whose progression is accelerated in the setting of obesity and host metabolic dysfunction, termed “metabo-oncology.” Citation Format: Peter Cornelius, John S. Petersen, Benjamin Mayes, David Turnquist, Kimberly Sullivan, Alfred Anderson-Villaluz, Robert Lutz, Sara Little, Andrew Slee, Bradley J. Carver, James Shanahan. Preclinical activity of SDX-7320 in mouse models of obesity and obesity-driven cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4919.

Significant role of fat tissue hormones in development of comorbid chronic pancreatitis and obesity

Aim is to consider the role of hormones in the adipose tissue of obesity mechanisms of metabolic syndrome, type 2 diabetes mellitus in chronic pancreatitis.&#x0D; Materials and methods. Literature review indicates the value of visceral fat in the development of insulin resistance, dyslipidemia, including atherogenic one, taking into account the possible infiltration of pancreatic tissue by adipocytes. Participation of some adipocytokines of adipose tissue in the development of obesity in chronic pancreatitis is highlighted. It is shown that in some cases the hormones of visceral adipose tissue, penetrating through the portal vein to the liver and then to the pancreas, aggravated the course of systemic chronic inflammation typical for the inherent chronic pancreatitis, formed steatosis and promoted development of fatty disease of the pancreas.&#x0D; Conclusion. Literary sources show the leading role of visceral adipose tissue and its hormones in the formation of obesity in chronic pancreatitis. Lipoidosis or steatosis develop due to the infiltration of the liver and pancreatic tissue by adipocytes. Upon the progression of the type 2 diabetes, fatty liver or pancreatic disease, or cancer of these organs may develop. Consequently, there is a strong need for a serious differentiated preventive and curative measures aimed at promoting a healthy lifestyle to improve the quality of life of patients suffering from chronic pancreatitis.

Association of adiponectin/leptin ratio with carbohydrate and lipid metabolism parameters in HIV-infected patients during antiretroviral therapy

ABSTRACTBackground: Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/leptin ratio (ALR) in correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV-infected patients during antiretroviral therapy (ART).Materials and Methods: We enrolled consecutive nondiabetic patients with confirmed HIV infection, undergoing stable ART regimens for at least six months. Blood samples were collected and tested for immunological and virological parameters, adiponectin and leptin, fasting insulin, fasting plasma glucose, fasting triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. ALR was computed for each patient. Resistance to insulin was assessed by calculating the Quantitative Insulin Sensitivity Check Index (QUICKI).Results: We enrolled 87 HIV-infected persons, with a mean age of 31.7 years (range: 18–65), including 47 men (mean age = 32.8 years) and 40 women (mean age = 30.5 years). The median value of ALR was 6.8 (interquartile range – IQR = 17.1). In male patients, ALR was inversely associated with the serum level of triglycerides (R = 0.285, p = 0.05), total cholesterol (R = 0.326, p = 0.02), and LDL cholesterol (R = 0.298, p = 0.04). Also for the male cohort, an increase in ALR seemed to improve insulin sensitivity (R = 0.323, p = 0.02) and serum HDL cholesterol (R = 0.597, p = 0.01). None of these correlations were observed in HIV-infected women.Conclusion: Adiponectin and leptin seem to play important but different gender-specific roles in the pathogenesis of lipid and glucose metabolism of HIV-infected patients undergoing antiretroviral therapy.Abbreviations: ALR, adiponectin/leptin ratio; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; QUICKI, Quantitative Insulin Sensitivity Check Index.

Role of hypothalamic leptin-LepRb signaling in NPY-CART-mediated appetite suppression in amphetamine-treated rats

Leptin is an adipose tissue hormone which plays an important role in regulating energy homeostasis. Amphetamine (AMPH) is a drug of appetite suppressant, which exerts its effect by decreasing the expression of hypothalamic neuropeptide Y (NPY) and increasing that of cocaine- and amphetamine-regulated transcript (CART). This study investigated whether leptin, the leptin receptor (LepRb) and the signal transducer and activator of transcription-3 (STAT3) were involved in NPY/CART-mediated appetite suppression in AMPH-treated rats. Rats were given AMPH daily for four days, and changes in the levels of blood leptin and hypothalamic NPY, CART, LepRb, Janus kinases 2 (JAK2), and STAT3 were assessed and compared. During the AMPH treatment, blood leptin levels and hypothalamic NPY expression decreased, with the largest reduction observed on Day 2. By contrast, the expression of hypothalamic CART, LepRb, JAK2, and STAT3 increased, with the maximum response on Day 2. Furthermore, the binding activity of pSTAT3/DNA increased and was expressed in similar pattern to that of CART, LepRb, and JAK2. An intracerebroventricular infusion of NPY antisense 60min prior to AMPH treatment increased the levels of leptin, as well as the expression in LepRb, JAK2, and CART, whereas an infusion of STAT3 antisense decreased these levels and the expression of these parameters. The results suggest that blood leptin and hypothalamic LepRb-JAK2-STAT3 signaling involved in NPY-CART-regulated appetite suppression in AMPH-treated rats. The findings may aid understanding the role of leptin-LepRb during the treatment of anorectic drugs.

The role of systemic inflammation in the pathogenesis of insulin resistance and metabolic syndrome in patients with chronic hepatitis C.

To determine the role of nonspecific inflammation in the formation of IR and metabolic syndrome in patients with chronic hepatitis C. The study included 205 patients with CHC aged 18 to 69 years. Patients with CHC are randomized into two groups depending on the presence of IR: group 1 - patients with a HOMA index ≥2.77, which corresponded to IR (n=110); group 2 (n=95). The levels of serum iron, C-reactive protein (CRP), serum ferritin and adipose tissue hormones [leptin, resistin, adiponectin and tumor necrosis factor-α (TNF-α)] were additionally investigated. At all stages of development of IR, nonspecific inflammation was detected (according to ferritin, CRP and serum iron), increasing with increasing HOMA index [Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)] (Matthews D., 1985), metabolic syndrome and its components. In the analysis of indicators in patients with chronic hepatitis C with a body mass index &lt;25 kg/m2, conjugacy of IR with low-intensity inflammation, high viral load and hypersecretion of TNF-α was detected. Given the high predictor role of CRP indicators in predicting IR, it should be used as a surrogate screening marker of IR in patients with chronic hepatitis C and should be actively treated for violations.

Changes in acyl ghrelin, insulin and leptin of young obese Indonesians following a 4-weeks weight loss program

Changes in acyl ghrelin, insulin and leptin of young obese Indonesians following a 4-weeks weight loss program