Hepatokines and Adipokines in Metabolic Syndrome

Hepatokines and adipokines are secretory proteins derived from hepatocytes and adipocytes, respectively. These proteins play a main role in the pathogenesis of metabolic syndrome (MetS), characterized by obesity, dysglycemia, insulin resistance, dyslipidemia, and hypertension. Adipose tissue and liver are important endocrine organs because they regulate metabolic homeostasis as well as inflammation because they secrete adipokines and hepatokines, respectively. These adipokines and hepatokines communicate their action through different autocrine, paracrine and endocrine pathways. Liver regulates systemic homeostasis and also glucose and lipid metabolism through hepatokines. Dysregulation of hepatokines can lead to progression toward MetS, type 2 diabetes (T2D), inflammation, hypertension, and other diseases. Obesity is now a worldwide epidemic. Increasing cases of obesity and obesity-associated metabolic syndrome has brought the focus on understanding the biology of adipocytes and the mechanisms occurring in adipose tissue of obese individuals. A lot of facts are now available on adipose tissue as well. Adipose tissue is now given the status of an endocrine organ. Recent evidence indicates that obesity contributes to systemic metabolic dysfunction. Adipose tissue plays a significant role in systemic metabolism by communicating with other central and peripheral organs via the production and secretion of a group of proteins known as adipokines. Adipokine levels regulate metabolic state of our body and are potent enough to have a direct impact upon energy homeostasis and systemic metabolism. Dysregulation of adipokines contribute to obesity, T2D, hypertension and several other pathological changes in various organs. This makes characterization of hepatokines and adipokines extremely important to understand the pathogenesis of MetS. Hepatokines such as fetuin-A and leukocyte cell-derived chemotaxin 2, and adipokines such as resistin, leptin, TNF-?, and adiponectin are some of the most studied proteins and they can modulate the manifestations of MetS. Detailed insight into the function and mechanism of these adipokines and hepatokines in the pathogenesis of MetS can show the path for devising better preventative and therapeutic strategies against this present-day pandemic.

Study of visfatin expression in acne patients in tissue and Serum

Background: Acne is a chronic inflammatory disease of the pilosebaceous units, of multifactorial pathogenesis, one of which could be an adipokine such as visfatin. Aim: The aim of this study was to study visfatin expression both in lesional skin and serum, of acne patients versus healthy controls. The secondary aim was to study the relationship of visfatin levels with dyslipidemia/metabolic syndrome. Methods: This study included 30 patients with moderate and severe acne vulgaris and 30 age- and sex-matched healthy controls. Serum and tissue visfatin were estimated by enzyme-linked immune-sorbent assay. Clinical and laboratory examinations were done to assess the anthropometric data and various criteria of metabolic syndrome. Results: Tissue and serum visfatin levels were significantly higher in patients as compared to healthy controls. Tissue visfatin levels were significantly higher than its serum levels in both patients and controls. Serum visfatin was significantly higher in overweight individuals. No correlations were found between tissue and serum visfatin levels in both patients and controls. Moreover, serum and tissue visfatin levels did not correlate to any of the lipid profile parameters or criteria of metabolic syndrome in acne patients. Limitations: The study had a small sample size and did not localize the exact source of tissue visfatin. Polycystic ovary syndrome PCOS was not evaluated. Conclusion: Visfatin is an important proinflammatory adipokine, with significantly higher expression in acne patients. Tissue rather than serum visfatin might play a key role in acne

The correlation between serum indexes and the renin-angiotensin-aldosterone system in children with simple obesity in Xinjiang area / 中华实用儿科临床杂志

Objective:To investigate the correlation between serum indexes of children with simple obesity in Xinjiang area and the renin-angiotensin-aldosterone (RAS)system, thus providing evidence to clarify the pathogenesis of childhood obesity.Methods:It was a cross-sectional study involving 41 children with simple obesity (case group) and 41 age-matched healthy children (control group) through the cluster random sampling in Tacheng area of Xinjiang.The mean age of in both groups was (10.04±1.66) years and (10.12±1.68) years, respectively.Serum adipokines, insulin level and RAS indexes between groups were compared by the Student′s t test.The correlation between serum adipokines and RAS activity in children with simple obesity was assessed by the Pearson′ s correlation test. Results:The serum adiponectin(APN) level[(7.90±1.96) μg/L vs.(8.87±1.61) μg/L, P=0.017]was significantly lower in case group than that of control group, while leptin[(6.81±1.88) ng/L vs.(5.87±1.79) ng/L, P=0.023]and resistin levels[(12.61±3.63) ng/L vs.(10.18±3.07) ng/L, P=0.002] were significantly higher.RAS indexes, including the renin[(35.78±10.08) ng/L vs.(29.24±10.69) ng/L, P=0.007], aldosterone (ALD)[(106.90±20.18) ng/L vs.(97.68±17.60) ng/L, P=0.028] and angiotensin-Ⅱ (Ang-Ⅱ)[(55.65±10.37) ng/L vs.(48.78±9.26) ng/L, P=0.002] levels were significantly higher in case group than those of control group.In the case group, serum APN level was negatively correlated with renin, ALD and Ang-Ⅱ levels ( r=-0.646, -0.752, -0.839, all P<0.001), while serum leptin and resistin levels were positively correlated with renin, ALD and Ang-Ⅱ levels ( r=0.940, 0.871, 0.875; 0.877, 0.892, 0.914, all P<0.001). Conclusions:Serum adipokine in school-age children with simple obesity in Xinjiang area is dysregulated, which interferes with the activity of RAS.

Effects of shift work on adipokines, inflammatory factors, and insulin sensitivity in non-overweight/obese women / 中华内分泌代谢杂志

Objective:To observe the effect of shift work on the stability of the circadian clock and insulin sensitivity in non-overweight/obese individuals with normal blood glucose, and explore underlying connection.Methods:Female shift working nurses in the Department of Blood Transplantation and non-shift working nurses in the Health Management Center in the First Affiliated Hospital of Zhengzhou University were divided into shift worker group (SW group) and non-shift worker group (NSW group). Serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)], adipokines (adiponectin, leptin, chemerin, visfatin), and melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). Realtime fluorescence quantitative PCR was performed to detect peripheral blood circadian clock genes circadian locomotor output cycles protein kaput(Clock) and brain and muscle ARNT-like protein 1(Bmal1). Cortisol and fasting insulin were measured by chemiluminescent microparticle immunoassay, and HbA 1C was measured by capillary electrophoresis. In addition, visceral fat area (VFA) was assessed with bioelectrical impedance analyzer, and mid-sleep time composite phase deviations (CPD) was calculated based on the International Physical Activity Short Questionnaire. Results:SW group had lower serum level of melatonin ( P=0.023) and higher cortisol ( P=0.001) than the NSW group, and altered mRNA expression of Clock and Bmal1 ( P=0.034, P=0.047). Fasting blood glucose and HbA 1C in the SW group, although in the normal range, had been higher than in the NSW group ( P=0.011, P=0.033). Although body mass index was normal in SW group, VFA had been higher than that of the NSW group ( P=0.010). And homeostasis model assessment for insulin resistance (HOMA-IR), IL-6, TNF-α, leptin, chemerin, and visfatin were significantly higher in the SW group than NSW group ( P=0.033, P=0.012, P=0.001, P=0.011, P=0.021, P=0.007). In addition, adjusting for body mass index and activity factors revealed a significant positive correlation between CPD and VFA ( r=0.434, P=0.049), inflammatory factors IL-6 ( r=0.514, P=0.017) and TNF-α ( r=0.700, P<0.001) and pro-inflammatory adipokines leptin ( r=0.473, P=0.030), chemerin ( r=0.439, P=0.047), visfatin ( r=0.521, P=0.015). Conclusion:Shift work can affect circadian clock, with increased visceral adiposity, pro-inflammatory adipokines, inflammatory factors and decreased insulin sensitivity in women without overweight/obese.

Research progress of adipokines and coronary heart disease / 中国医师杂志

Adipokines play an important role in judging the severity and prognosis of coronary heart disease. In recent years, a series of studies have further proved the correlation between adipokines and coronary heart disease. Adipokines can be included in the risk stratification of patients with coronary heart disease and guide the formulation of clinical diagnosis and treatment strategies, and may become a potential therapeutic target of coronary heart disease. This paper mainly summarizes the role of adipokines in the clinical diagnosis and treatment of coronary heart disease.

Progress on the roles of adipokines in sepsis organ injury / 中国小儿急救医学

Sepsis is a serious life-threatening organ dysfunction disease caused by the body′s response to infection, which is the main cause of death in patients admitted to ICU.The occurrence, development and prognosis of sepsis are closely related to metabolism and regulation of inflammatory response.Adipose tissue not only participates in energy storage and metabolism, but also, as an important endocrine organ, secretes a variety of adipokines with pro-inflammatory or anti-inflammatory activities, and thus participates in the occurrence and development of sepsis.There are many kinds of adipokines, and different adipokines play different roles in sepsis and sepsis-related organ damage.Some adipokines such as adiponectin, adipokine complement Clq/tumor necrosis factor-associated protein 3, vaspin, irisin and Apelin are closely related with the pathogenesis and prognosis of organ injury in sepsis.

The Regulation of Adipokines on Metabolism / 中国生物化学与分子生物学报

Excess energy is stored in adipose tissues in the form of triglycerides (TGs), which are hydrolyzed to free fatty acids(FFAs) to meet energy requirement under fasting conditions. In addition to thermogenesis and organ protection,the adipose tissue is now recognized as an important endocrine organ. The proteins secreted by adipocytes are termed as adipokines. Adipokines appear to be involved in such cellular processes as energy intake and energy expenditure,glucose and lipid metabolism,as well as anti- and pro-inflammatory effects via autocrine, paracrine and endocrine. At the systemic level, adipokines regulate various biological processes in target organs,including the brain,liver,muscle,vasculature,heart and pancreas, immune system, and others. Adipokines exert specific effects on glucose and lipid metabolism, including glucose metabolism (leptin, adiponectin, resistin), insulin sensitivity [leptin, adiponectin,zinc-α2-glycoprotein(ZAG)],adipogenesis [bone morphogenetic protein 4 (BMP4)] and other biological processes. However,a linkage between adipose tissue dysfunction and metabolic disorders needs further clarification. Altered expression or secretion of adipokines under adipose tissue dysfunction may contribute to a spectrum of obesity-associated diseases. Preclinical and clinical studies show that activating or inhibiting the signaling of specific adipokines could be an approach suitable to metabolic disease intervention. The current article reviews the effects of some adipokines on metabolism in order to deepen our understanding of the adipokines function.

Measuring visfatin levels in saliva: an alternative approach to gestational diabetes screening

ABSTRACT Objective: Oral glucose tolerance testing (OGTT) is the current recommended approach for the diagnosis of gestational diabetes mellitus (GDM). Visfatin is a type of novel adipokine of interest that mostly participates in glucose metabolism and inflammatory processes. We aim to identify a screening technique for GDM using salivary visfatin levels and to establish this technique's value as a screening method compared to OGTT. Materials and methods: This is a cross-sectional case-control study. The cohort was formed from the saliva samples of pregnant patients in their 24th through 28th weeks of gestation. Patients were divided into two groups depending on their GDM status. OGTT and visfatin test results were compared and subjected to further analysis to establish a cutoff value for visfatin testing. Results: ELISA results indicated a significant difference between patients with GDM compared to patients without GDM; the values were 18.89 ± 9.59 and 12.44 ± 8.75, respectively (p: 0.007). A cutoff value of 10.5 ng/mL can be used to detect GDM with 78% sensitivity and 51% specificity. Conclusion: Salivary visfatin levels were significantly higher in patients with GDM. The existence of a differential in the concentration of visfatin in saliva can be utilized to develop a new screening method for GDM.

Exogenous phosphatidic acid reduces acetaminophen-induced liver injury in mice by activating hepatic interleukin-6 signaling through inter-organ crosstalk

We previously demonstrated that endogenous phosphatidic acid (PA) promotes liver regeneration after acetaminophen (APAP) hepatotoxicity. Here, we hypothesized that exogenous PA is also beneficial. To test that, we treated mice with a toxic APAP dose at 0 h, followed by PA or vehicle (Veh) post-treatment. We then collected blood and liver at 6, 24, and 52 h. Post-treatment with PA 2 h after APAP protected against liver injury at 6 h, and the combination of PA and

Research progress on the role of adipokines in intervertebral disc degeneration / 中国修复重建外科杂志

Objective: To review the research progress of the role and mechanism of adipokines in intervertebral disc degeneration (IVDD) in recent years. Methods: The domestic and foreign literature related to adipokines in the process of IVDD was extensively reviewed. The types and functions of adipokines, the role and mechanism in the process of IVDD, and the application prospects of intervertebral disc biotherapy were reviewed. Results: As a kind of bioactive substance secreted by adipose tissue, adipokine plays an important role in bone and joint diseases, metabolic diseases, and breast cancer. During IVDD, most adipokines can activate multiple signaling pathways by binding to autoreceptors, cause the proliferation and apoptosis of cells and proinflammatory and anti-inflammatory factors parasecretions in the intervertebral disc, and lead to imbalance of intradiscal metabolism and establishment of the initial inflammatory environment, and finally cause the IVDD. Conclusion: Adipokines, as a biologically active substance with metabolic and immunomodulatory functions, play important roles in the occurrence, development, and biological treatment of IVDD.

Insulin resistance is associated with Sfrp5 in obstructive sleep apnea / Resistência à insulina está associada à Sfrp5 na apneia obstrutiva do sono

Abstract Introduction: Obstructive sleep apnea, a common disease, is usually complicated by insulin resistance and type 2 diabetes mellitus. Adipokine is considered to play an important role in the development of insulin resistance and type 2 diabetes mellitus in obstructive sleep apnea. Objective: To assess whether secreted frizzled-related protein 5, a new adipokine, is involved in untreated obstructive sleep apnea patients. Methods: Seventy-six subjects with obstructive sleep apnea and thirty-three control subjects without obstructive sleep apnea were recruited and matched in terms of body mass index and age. The fasting secreted frizzled-related protein 5 plasma concentration was tested using ELISA. In addition, the correlation between secreted frizzled-related protein 5 and the homeostasis model assessment of insulin resistance was obtained. Multiple linear regression analysis models with stepwise selection were performed to determine the independent associations between various factors and secreted frizzled-related protein 5. Results: Plasma secreted frizzled-related protein 5 levels were significantly lower in the obstructive sleep apnea group than in the control group (obstructive sleep apnea group: 28.44 ± 13.25 ng/L; control group: 34.16 ± 13.51 ng/L; p = 0.023). In addition, secreted frizzled-related protein 5 was negatively correlated with homeostasis model assessment of insulin resistance but positively correlated with the mean and lowest oxygen saturation with or without adjusting for age, gender, body mass index, neck circumference, waist circumference and waist-to-hip ratio. The multiple linear regression analysis showed there was an independent negative association between secreted frizzled-related protein 5 and homeostasis model assessment of insulin resistance. Conclusion: Secreted frizzled-related protein 5 was involved in obstructive sleep apnea and the decrease in secreted frizzled-related protein 5 was directly proportional to the severity of obstructive sleep apnea. There was an independent negative correlation between homeostasis model assessment of insulin resistance and secreted frizzled-related protein 5 in the obstructive sleep apnea group. Secreted frizzled-related protein 5 might be a therapeutic target for insulin resistance in obstructive sleep apnea.

Resumo Introdução: A apneia obstrutiva do sono, uma doença comum, é geralmente complicada com resistência à insulina e diabetes melito tipo 2. Acredita-se que a adipocina possa ter um papel importante no desenvolvimento de resistência à insulina e diabetes melito tipo 2 na apneia obstrutiva do sono. Objetivo: Avaliar se a proteína secretada relacionada ao receptor frizzled-5, uma nova adipocina, está envolvida em pacientes com apneia obstrutiva do sono não tratada. Método: Foram recrutados 76 indivíduos com apneia obstrutiva do sono e 33 indivíduos controle sem apneia obstrutiva do sono e pareados em relação a índice de massa corporal e idade. A concentração plasmática de proteína secretada relacionada ao receptor frizzled-5 foi testada em jejum com o teste Elisa. Além disso, obteve-se correlação entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Modelos de análise de regressão linear múltipla com seleção stepwise foram feitos para determinar as associações independentes entre vários fatores e a proteína secretada relacionada ao receptor frizzled-5. Resultados: Os níveis plasmáticos de proteína secretada relacionada ao receptor frizzled-5 foram significativamente menores no grupo com apneia obstrutiva do sono do que no grupo controle (grupo com apneia obstrutiva do sono: 28,44 ± 13,25 ng/L; grupo controle: 34,16 ± 13,51 ng/L; p = 0,023). Além disso, a proteína secretada relacionada ao receptor frizzled-5 foi correlacionada negativamente com o modelo de avaliação da homeostase de resistência à insulina, mas se correlacionou positivamente com a média e a saturação mínima de oxigênio com ou sem ajuste para idade, gênero, índice de massa corporal, circunferência do pescoço, circunferência da cintura e relação cintura-quadril. A análise de regressão linear múltipla mostrou que houve uma associação negativa independente entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Conclusões: A proteína secretada relacionada ao receptor frizzled-5 esteve envolvida na apneia obstrutiva do sono e sua diminuição foi diretamente proporcional à gravidade da apneia obstrutiva do sono. Houve uma correlação negativa independente entre o modelo de avaliação da homeostase de resistência à insulina e a proteína secretada relacionada ao receptor frizzled-5 no grupo da apneia obstrutiva do sono. A proteína secretada relacionada ao receptor frizzled-5 pode ser um alvo terapêutico para a resistência à insulina na apneia obstrutiva do sono.

Gingival crevicular fluid resistin levels in chronic periodontitis with type 2 diabetes before and after non-surgical periodontal therapy: A clinico-biochemical study

Aim: Periodontitis and diabetes mellitus share a bidirectional relationship. Resistin is an adipocytokine shown to be associated with type 2 diabetes mellitus. Hence, the present study aims to estimate the effect of non-surgical periodontal therapy (NSPT) on GCF resistin levels in healthy individuals with gingivitis and well controlled diabetics with periodontitis, and correlate the same with HbA1c levels of the diabetic subjects. Materials and Methods: The present study was a comparative interventional trial set in Department of Periodontics, the Oxford Dental College, Bangalore. Forty subjects participated in the study and were divided into two groups; group I (healthy individuals with gingivitis) and group II (diabetic individuals with mild to moderate periodontitis). Periodontal parameters were assessed and GCF was collected and analysed for resistin before and 3 months after NSPT. Statistical Analysis: All the analysis was done using SPSS version 18. A P value of < 0.05 was considered statistically significant. Results: A significant difference was observed in GCF resistin concentrations between the two groups at baseline, wherein group II had significantly higher values. Following NSPT, there was a significant reduction in GCF resistin concentrations in both the groups, however intergroup comparison showed no difference in the amount of reduction. When all samples were analysed together, no significant correlation could be found between resistin and the parameters assessed. Conclusion: Resistin levels are increased in diabetes related periodontitis. However, post treatment a similar response can be seen between healthy and well controlled diabetics. Hence, resistin can be used as an inflammatory biomarker for diabetes related periodontal disease.

Carbohydrate and lipid disorders and adipokines levels in relation to body mass index in hypertensive patients / Trastorno del metabolismo de carbohidratos y lípidos y los niveles de adipoquinas en relación con el índice de masa corporal en pacientes con hipertensión

Abstract: Obesity is considered as a valid risk factor for cardiovascular disease, due to the fact that the risk of morbidity and mortality from various causes in obese people is significantly higher. Exact mechanisms of metabolic disorders in hypertension with obesity is still discussible. The aim of the study - to determine the peculiarities of carbohydrate, lipid metabolism changes and activity of adipokines and interleukin-22, in patients with hypertension according to nutritional status. Methods: 80 patients (37 males and 43 females) with essential hypertension (EH) of average age 60.17 years were examined. Carbohydrate, lipid profiles, apolipoprotein B (apo B), tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), adiponectin, interleukin-22 (IL-22) were estimated. Results: In patients with EH and obesity was found carbohydrates metabolism abnormalities, that was manifested as hyperinsulinemia, glucose and HbA1c levels elevation and insulin resistance (according to HOMA index). Lipid metabolism disorders were observed as valid increasing of triglycerides and apo B. Body mass index elevation was associated with progressive increasing of TNF-α and PAI-1 concentration with reducing of adiponectin level in the patients with EH. Positive relationships between TNF- and HbA1c, apo B; PAI-1 with glucose levels: negative correlation adiponectin with body mass and waist to hip ratio were detected in the patients with obesity associated (BMI ≥ 30 kg/m2) EH. Positive significant correlations between apo B and insulin levels, HOMA index, and TNF-α concentration were defined. IL-22 in overweigh and obese patients was significantly higher, correlates negatively with HDL-C. Conclusion: In patients with EH and obesity the adipokine dysfunction was revealed, that correlates with carbohydrate and lipid parameters that indicate increased proinflammatory and prothrombogenic processes.(AU)

Resumen: La obesidad se considera un factor de riesgo válido para las enfermedades cardiovasculares, debido a que el riesgo de morbilidad y mortalidad por diversas causas en personas obesas es significativamente mayor. Los mecanismos exactos de los trastornos metabólicos en la hipertensión con obesidad todavía son discutibles. El objetivo del estudio - determinar las peculiaridades de los carbohidratos, los cambios en el metabolismo de los lípidos y la actividad de las adipoquinas y la interleucina 22, en pacientes con hipertensión según el estado nutricional. Métodos: Se examinaron 80 pacientes (37 hombres y 43 mujeres) con hipertensión esencial (HE) de edad promedio de 60.17 años. Se estimaron los perfiles de carbohidratos, lípidos, apolipoproteína B (apo B), factor de necrosis tumoral-α (TNF-α), inhibidor activador del plasminógeno-1 (PAI-1), adiponectina, interleucina-22 (IL-22). Resultados: En pacientes con HE y obesidad se encontraron anomalías en el metabolismo de los carbohidratos, que se manifestaron como hiperinsulinemia, elevación de los niveles de glucosa y HbA1c y resistencia a la insulina (según el índice HOMA). Se observaron trastornos del metabolismo de los lípidos como aumento válido de triglicéridos y apo B. La elevación del índice de masa corporal se asoció con el aumento progresivo de la concentración de TNF-α y PAI-1 con la reducción del nivel de adiponectina en los pacientes con HE. Relaciones positivas entre TNF- y HbA1c, apo B; PAI-1 con niveles de glucosa: se detectaron correlaciones negativas de adiponectina con masa corporal y relación cintura-cadera en los pacientes con obesidad (IMC ≥ kg/m2) asociada con HE. Se definieron correlaciones positivas significativas entre los niveles de apo B e insulina, el índice HOMA y la concentración de TNF-α. La IL-22 en pacientes con sobrepeso y obesos fue significativamente mayor, se correlaciona negativamente con HDL-C. Conclusión: En pacientes con HE y obesidad se reveló la disfunción de la adipoquina, que se correlaciona con parámetros de carbohidratos y lípidos que indican un aumento de los procesos proinflamatorios y protrombogénicos.(AU)

Effects of high-fat diet induced obesity on tissue zinc concentrations and zinc transporter expressions in mice / 한국영양학회지

PURPOSE: Obesity is often associated with disturbances in the mineral metabolism. The purpose of this study was to investigate the effects of high-fat diet-induced obesity on tissue zinc concentrations and zinc transporter expressions in mice. METHODS: C57BL/6J male mice were fed either a control diet (10% energy from fat, control group) or a high-fat diet (45% energy from fat, obese group) for 15 weeks. The zinc concentrations in the serum, stool, and various tissues were measured by inductively coupled plasma (ICP)-atomic emission spectrophotometry or ICP-mass spectrophotometry. The levels of zinc transporter mRNAs in the liver, duodenum, and pancreas were measured by real-time RT-PCR. The levels of serum adipokines, such as leptin and IL-6, were determined. RESULTS: The total body weight, adipose tissue weight, and hepatic TG and cholesterol concentrations were significantly higher in the obese group, as compared to the control group. The obese group had significantly higher levels of serum leptin and pro-inflammatory IL-6 concentrations, and had significantly lower levels of serum alkaline phosphatase activity. The zinc concentrations of the liver, kidney, duodenum, and pancreas were all significantly lower in the obese group than in the control group. On the other hand, the fecal zinc concentrations were significantly higher in the obese group than in the control group. The serum zinc concentrations were not significantly different between the two groups. The ZnT1 mRNA levels of the liver and the pancreas were significantly higher in the obese group, as compared to the control group. Hepatic Zip10 mRNA was also increased in the obese group. CONCLUSION: Our study findings suggest that obesity increases fecal zinc excretion and lowers the tissue zinc concentrations, which may be associated with alterations in the zinc transporter expressions.

Relationship between plasma adiponectin, visfatin, leptin, and resistin levels and the onset of colonic polyps in prediabetes / 中华内分泌代谢杂志

Objective To explore the relationship between plasma adiponectin, visfatin, leptin, and resistin levels, and the onset of colonic polyps in prediabetes subjects. Methods A total of 468 prediabetes subjects, who received colonoscopy examination, were enrolled in this study, including 248 cases of colon polyps (polyps group with prediabetes) and 220 cases without colonic mucosal lesions ( polyps-free group with prediabetes). According to the clinical characteristics of colonic polyps, colonic polyps patients with prediabetes were subdivided into single polyp group, multiple polyps group, low-risk polyps group, and high-risk polyps group, respectively. In addition, 108 subjects with normal glucose tolerance, who were matched with prediabetes subjects on gender and age, were selected as control group, and 46 cases of them were refered to polyps group with normal glucose tolerance and 62 cases were refered to polyps-free group with normal glucose. Plasma adiponectin, visfatin, leptin, and resistin levels were measured in all subjects, and related risk factors of colonic polyps in prediabetes patients were analyzed. Results Not only in normal glucose tolerance subjects, but also in prediabetes subjects, plasma visfatin levels in polyps group were significantly higher than those in polyps-free group (P＜0.05), and plasma adiponectin levels were significantly lower than those in polyps-free group [normal glucose tolerance (9.8±4.8 vs 13.3±3.9)mg/L, P＜0.05; prediabetes (5.6 ± 3.7 vs 9.2 ± 4.4)mg/L, P＜0.01], respectively. However, no significant difference in the plasma leptin and resistin levels were observed between polyps-free group and polyps group ( both P＞0. 05), respectively. In addition, in prediabetes subjects, plasma visfatin levels increased (P＜0.05) and adiponectin levels decreased significantly [(4.3 ± 2.6 vs 6.7 ± 3.9) mg/L, P＜0.05] in multiple polyps group than in single polyp group. Nevertheless, there were no significant differences in plasma leptin and resistin levels between two groups (both P＞0.05). Moreover, plasma adiponectin levels decreased significantly in high-risk polyps group with prediabetes than in low-risk polyps group with prediabetes[(3.7±2.9vs7.4±3.5)mg/L,P＜0.05].Meanwhile,noneofplasmavisfatin,leptin,andresistinlevels had shown significant difference between two groups (all P＞0.05). The multivariate logistic regression analysis found that adiponectin was an independent protective factor for colon polyps, multiple colon polyps and high-risk colon polyps. Conclusion The changes of plasma adiponectin levels might be associated with onset of colonic polyps in prediabetes.

Effects of TLR4 knockout on immune cells and adipokines in mouse visceral adipose tissue / 中国免疫学杂志

Objective:To investigate the effects of TLR4 knockout on immune cells and adipokines in mouse visceral adipose tissue.Methods: Cells were isolated from the spleen and epididymal adipose tissue of 20-week-old male wild type mice C57BL/6 and TLR4-/-.The expression of F4/80,CD11b,CD11c,CD3,CD4 and CD8 in these cells were analyzed by flow cytometry.The expression of IL-6,HMGB1,TNF-α,adiponectin and resistin in epididymal adipose tissue were detected by qPCR.Results: Compared with wild type C57BL/6 mice,the percentage of M1 macrophage which marked F4/80+CD11b+CD11c+ in spleen and epididymal adipose tissue of TLR4-/-mice increased(P<0.05) greatly,while that of M2 macrophage which marked F4/80+CD11b+CD11c-was decreased(P<0.05)significantly.This trend was more remarkable in epididymal adipose tissue than in spleen(P<0.05).In epididymal adipose tissue,the percentage of CD4+T cells decreased but that of CD8+T cells increased in TLR4-/-mice.Moreover,the high-level expressions of IL-6,HMGB1,resistin were found in epididymal adipose tissue of TLR4-/-mice.However,the expressions of TNF-α and adiponectin decreased obviously.Conclusion: TLR4 knock-out could lead to a disorder in adipokine and immune cells in visceral adipose tissue.

Research progress on glycolipid metabolism regulating of FGF19 and FGF21 in adipose tissue / 国际生物医学工程杂志

Adipose tissue is not only an energy storage organ, but also an endocrine organ involved in metabolic processes. It has the function of secreting various adipokines, such as leptin, adiponectin, etc. Adipose tissue and adipokines are involved in the regulation of glucose and lipid metabolism, which show great value in the study of metabolic diseases such as diabetes and obesity. As a fibroblast growth factor (FGFs), the family of protein hormone-like factors 19 (FGF19) and FGF21 have roles in decreasing body weight, increasing insulin sensitivity, improving blood lipid spectrum, etc. FGF19 and FGF21 are promising target drugs for the treatment of metabolic diseases. The recent research progress on the glycolipid metabolism regulating of FGF19 and FGF21 in adipose tissue were summarized and the application prospects were reviewed.

Relationship Between Angiotensin Ⅱ , Secreted Frizzled-related Protein 5 and Rat's Cardiomyocyte Hypertrophy in Vitro / 中国循环杂志

Objective: To investigate the expression and effect of secreted frizzled-related protein 5 (sFRP5) in rat's cardiomyocyte hypertrophy in vitro. Methods: Neonatal rat's ventricular myocytes were cultured in vitro, cardiomyocyte hypertrophy was induced by Ang Ⅱ. Telmisartan and PD123319 were used to block angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) respectively. RT-PCR and Western-blot analysis were conducted to examine the expressions of sFRP5, BNP and TNF-α. Results: sFRP5 was expressed in cardiomyocytes. The mRNA and protein expressions of sFRP5, protein expression of BNP were increased by prolonged time of AngⅡ treatment, the maximum expression was observed at 48 h, P<0.05. Compared with Ang Ⅱ (10-6mol/L) group, the mRNA and protein expressions of sFRP5 in Ang Ⅱ +Telmisartan (10 μmol/L) group were decreased, P<0.05, those expressions were similar in Ang Ⅱ +PD123319 (10 μmol/L) group, P>0.05. Compared with AngⅡ (10-6 mo1/L)+sFRP5 (0 ng/ml) group, protein expressions of BNP and TNF-α were decreased inAng Ⅱ (10-6 mo1/L)+sFRP5 (10 ng/ml) group and in Ang Ⅱ (10-6 mo1/L)+sFRP5 (100 ng/ml) group respectively, P<0.05. Conclusion: For in vitro process of Ang Ⅱ induced neonatal rat's cardiomyocyte hypertrophy, using Ang Ⅱ receptor could up-regulate sFRP5 expression and sFRP5 plays an important role in cardiomyocyte hypertrophy.

Role of atorvastatin in improving the inflammation-induced adipokine imbalance in mice with acute myocardial infarction / 中南大学学报(医学版)

Objective:To investigate the effect of acute myocardial infarction (AMI)-activated inflammation on adipokine imbalance and the therapeutic effects of statin.Methods:A total of 32 C57BL/6 mice were divided into 4 groups:a sham group,an AMI group,a low-dose atorvastatin [2 mg/(kg.d)] group and a high-dose atorvastatin [20 mg/(kg.d)] group.AMI models were established by surgical coronary artery ligation.Plasma levels of high sensitive C reaction protein (hs-CRP),adiponectin and resistin were measured.Adiponectin and resistin expressions were determined.In addition,mouse 3T3-L1 preadipocytes in vitro were differentiated and they were stimulated by oxidized low density lipoprotein (ox-LDL).The protein expressions of adiponectin and resistin in adipocytes were detected.The effects of atorvastatin on ox-LDL-induced adipokine imbalance in adipocytes were identified.Results:The plasma levels of hs-CRP and resistin in AMI mice were significantly increased,whereas the plasma levels of adiponectin were remarkably decreased.However,atorvastatin treatment blocked the changes in the plasma levels of hs-CRP,resistin and adiponectin in AMI mice in a dose-dependent manner.Consistent findings regarding the adipose expressions of the two adipokines were obtained.The plasma levels of hs-CRP were positively correlated with resistin but negatively with adiponectin.In vitro study,ox-LDL increased resistin protein and adiponectin expressions in adipocytes,which were dose-dependently reversed by atorvastatin.Conclusion:Inflammation activation in AMI mice leads to adipokine imbalance.Atorvastatin ameliorates the AMI-induced adipokine imbalance via anti-inflammation.

Serum leptin levens and hepatocellular carcinoma: review article / Níveis séricos de leptina e carcinoma hepatocelular: revisão da literatura

ABSTRACT Introduction: Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. Objective: To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Method: Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. Results: After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Conclusion: Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported.

RESUMO Introdução: O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Objetivo: Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Método: Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Resultado: Após avaliação individual dos artigos selecionaram-se sete estudos. Os resultados ainda são inconsistentes e contraditórios, e a leptina pode estar efetivamente envolvida na ocorrência e no desenvolvimento do carcinoma hepatocelular. Conclusão: Faz-se necessário o desenvolvimento de estudos prospectivos, bem desenhados e conduzidos sobre o papel e mecanismos específicos deste hormônio em pacientes com carcinoma hepatocelular para que novas correlações sejam devidamente comprovadas.