脂联素、瘦素、胰岛素的调节与女性单纯性肥胖

目的 :探讨女性单纯性肥胖患者血液中瘦素 (Leptin)、脂联素 (Adiponectin ,Adi)、胰岛素 (Insulin)等水平变化及与肥胖程度的变化关系、相关关系及对肥胖的调节。方法 :女性肥胖前期患者 [BMI =(2 3～ 2 4 9)kg/m2 ]4 8例 ,肥胖者 (BMI≥ 2 5kg/m2 ) 4 0例 ,对照组 [BMI=(1 8～ 2 2 9)kg/m2 ]4 2例。用放射免疫分析 (RIA)测定血浆瘦素、脂联素、胰岛素水平。各变量之间的关系先进行相关分析 ,然后用直线回归和多元性线回归分析。结果 :肥胖前期组和肥胖组血清瘦素、胰岛素水平均明显高于正常对照组 (P <0 .0 1 ) ,且各变量值之间呈密切相关 ;血清脂联素水平则明显低于正常对照组。其中 ,血清水平变化与BMI呈直线正相关的激素为 :瘦素、胰岛素 ,随着BMI升高而升高 ;与BMI呈直线负相关的激素有脂联素 ,随着BMI升高而降低。在各种激素的相关关系中 ,瘦素、脂联素的变化与其他激素呈明显相关。结论 :随着BMI升高 ,机体对瘦素抵抗 ,使患者血浆瘦素水平明显升高 ,并出现高胰岛素血症 ;激素间的互相作用使“瘦素 -胰岛素”平衡环、“胰岛素 -脂联素”调节环、“瘦素 -胰岛素”调节环等反馈环自身适应性调节 ,当机体体重大量病理性增加后 ,其机体内分泌体系为减少体内能量的蓄积作出适应性调节 ,这会改变各种     

Immunological characteristics and management considerations in obese patients with asthma

Obesity is associated with severe, poorly controlled asthma that does not respond as well to therapy as asthma in leaner asthmatics. Important insights gained from animal models of obesity and asthma suggests that different forms of obesity may lead to different manifestations of airway disease: obesity is associated with both innate increased airway reactivity and altered responses to aeroallergen and pollutant challenges. In humans, at least two broad groups of obese asthmatics have been recognized: one that is likely unique to obesity and another that is likely lean allergic asthma much complicated by obesity. This article will discuss what we have learned about the immunological and pathophysiological basis of asthma in obesity from animal and human studies, and how this might guide therapy.     

Role of Adipokines and Hormones of Obesity in Childhood Asthma

Purpose

The aim of this study was to evaluate serum levels of leptin, ghrelin, and adiponectin in obese and non-obese children with asthma and in healthy non-asthmatic children, and analyze their relationships with clinical outcomes.

Methods

This study enrolled 40 obese and 51 non-obese children with asthma and 20 healthy children. Body mass index and serum leptin, ghrelin, and adiponectin levels were determined in all children. Asthma symptom scores and lung function test results were recorded for subjects with asthma.

Results

Serum leptin levels (11.8±7.9, 5.3±6.8, and 2.1±2.4 ng/mL in the obese asthmatic, non-obese asthmatic, and control groups, respectively) and adiponectin levels (12,586.2±3,724.1; 18,089.3±6,452.3; and 20,297.5±3,680.7 ng/mL, respectively) differed significantly among the groups (P<0.001 for all). Mean ghrelin levels were 196.1±96.8 and 311.9±352.8 pg/mL in the obese and non-obese asthmatic groups, respectively, and 348.8±146.4 pg/mL in the control group (P=0.001). The asthma symptom score was significantly higher in the obese children with asthma than in the non-obese children with asthma (P<0.001). Leptin and adiponectin levels were correlated with the asthma symptom score in non-obese children with asthma (r=0.34 and r=-0.62, respectively).

Conclusions

Obesity leads to more severe asthma symptoms in children. Moreover, leptin, adiponectin, and ghrelin may play important roles in the inflammatory pathogenesis of asthma and obesity co-morbidity.     

Adipo/AMPK信号通路的下调参与肥胖型哮喘小鼠的发病

目的探讨Adipo/AMPK信号通路在肥胖型哮喘气道炎性反应及气道高反应中的作用及机制。方法将40只SPF级C57BL/6小鼠随机分为正常体质量组(A)、哮喘组(B)、肥胖组(C)和肥胖哮喘组(D),A组进行普通饲料喂养+0.9%氯化钠溶液致敏激发,B组进行普通饲料喂养+OVA/Al(OH)3致敏激发,C组予以高脂饲料喂养+0.9%氯化钠溶液致敏激发,D组则给予高脂饲料喂养+OVA/Al(OH)_3致敏激发。测定各组小鼠气道阻力,HE染色观察肺组织病理改变,ELISA法检测血清Adipo水平,qRT-PCR法检测肺组织Adipo、AdipoR1及AMPKαmRNA的表达,Western blot法检测肺组织Adipo、AMPKα和p AMPKα蛋白的表达水平。结果 C组和D组小鼠体质量增长明显(P0.01);与A组相比,B组、C组和D组总气道阻力(RL)增高、肺部炎性反应加重,D组增高最显著(P0.05);同时,B组、C组和D组小鼠肺组织Adipo mRNA、AdipoR1 mRNA、Adipo蛋白和p AMPKα蛋白的表达较A组显著降低(P0.05)。结论肥胖型哮喘小鼠气道反应增高、气道炎性反应加重可能与Adipo/AMPK信号通路的下调有关。     

Juvenile Obesity Aggravates Disease Severity in a Rat Model of Atopic Dermatitis

Purpose

There is increasing epidemiological evidence of an association between childhood obesity and atopic dermatitis, but little is known about the underlying mechanism(s). In the present study, we used a rat model of atopic dermatitis to assess whether juvenile obesity, induced by reduction of litter size, aggravated the signs of atopic dermatitis and, if so, whether this aggravation was associated with changes in plasma concentration of adipokines, such as leptin and adiponectin.

Methods

Dermatitis was induced by neonatal capsaicin treatment. Body weight, dermatitis score, serum IgE, skin nerve growth factor (NGF), serum leptin and adiponectin, and cytokine mRNA expression in the skin lesion were compared between small (SL, 5 pups) and large litters (LL, 15 pups).

Results

The body weight of juvenile rats up to 6 weeks of age was significantly heavier in the SL group, compared with those in the LL group. The SL group showed more robust development of dermatitis, and higher levels of serum IgE and skin NGF than the LL group. Additionally, the SL group demonstrated higher levels of leptin and pro-inflammatory cytokine mRNA but lower levels of adiponectin than the LL group.

Conclusions

These results suggest a causal link between a decrease in immunological tolerance, induced by juvenile obesity, and aggravation of atopic dermatitis.     

女性小儿单纯肥胖症患者血清leptin及其相关因子含量的相关性

目的：探讨了女性小儿单纯性肥胖症患儿血清瘦素（leptin）、神经肽Y（NPY）和脂联素（ADP）的含量变化及相关性。方法：应用放射免疫分析对32例女性小儿单纯肥胖症患者进行了血清leptin、NPY和ADP水平检测,并与35名正常女性小儿作比较。结果：女性小儿单纯性肥胖症患者血清leptin、NPY水平非常显著地高于正常女童组（P〈0．01）,而ADP水平则非常显著地低于正常女童组（P〈0．01）,且血清leptin水平与NPY水平呈明显的正相关（r=0．6014,P〈0．01）,与ADP水平呈明显的负相关（r=-0．4786,P〈0．01）。结论：检测女性小儿单纯性肥胖症患儿血清leptin、NPY和ADP水平的变化对了解病情、指导临床实践均具有一定的临床实用价值。     

Obesity affects peripheral lymphoid organs immune response in murine asthma model

Asthma and obesity present rising incidence, and their concomitance is a reason for concern, as obese individuals are usually resistant to conventional asthma treatments and have more exacerbation episodes. Obesity affects several features in the lungs during asthma onset, shifting the T helper type 2 (Th2)/eosinophilic response towards a Th17/neutrophilic profile. Moreover, those individuals can present reduced atopy and delayed cytokine production. However, the impact of obesity on follicular helper T (Tfh) cells and B cells that could potentially result in antibody production disturbances are still unclear. Therefore, we aimed to assess the peripheral response to ovalbumin (OVA) in a concomitant model of obesity and asthma. Pulmonary allergy was induced, in both lean and obese female BALB/c mice, through OVA sensitizations and challenges. Mediastinal lymph nodes (MLNs) and spleen were processed for immunophenotyping. Lung was used for standard allergy analysis. Obese-allergic mice produced less anti-OVA IgE and more IgG2a than lean-allergic mice. Dendritic cells (CD11c⁺ MHCII^high) expressed less CD86 and more PDL1 in obese-allergic mice compared with lean-allergic mice, in the MLNs. Meanwhile, B cells (CD19⁺ CD40⁺) were more frequent and the amount of PDL1/PD1⁺ cells was diminished by obesity, with the opposite effects in the spleen. Tfh cells (CD3⁺ CD4⁺ CXCR5⁺ PD1⁺) expressing FoxP3 were more frequent in obese mice, associated with the predominance of Th (CD3⁺ CD4⁺) cells expressing interleukin-4/GATA3 in the MLNs and interleukin-17A/RORγT in the spleen. Those modifications to the main components of the germinal centers could be resulting in the increased IgG2a production, which – associated with the Th17/neutrophilic profile – contributes to asthma worsening and represents an important target for future treatment strategies.     

Differential expression of adipokines in the synovium and infrapatellar fat pad of osteoarthritis patients with and without metabolic syndrome

ABSTRACT

Objective: To evaluate the expression levels of adipokines in the synovium and infrapatellar fat pad (IPFP) in osteoarthritis (OA) patients with and without metabolic syndrome (MetS).

Methods: 120 female patients with OA were enrolled, and 60 healthy women matched body mass index, age, and sex, served as controls. Adipokines levels were measured using a sandwich enzyme-linked immunosorbent assay of the serum of all participants and synovial fluid (SF) of OA patients. Local expression levels of adipokines in the synovium and IPFP were examined by immunohistochemical analysis. The amount of adipokine proteins was analyzed using Western blot, and adipokine mRNA expressions were determined via quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Serum leptin levels were significantly higher in the non-MetS-OA group than those in controls (7.97 vs. 4.24 ng/ml, p< 0.001), and even higher leptin levels were found in the MetS-OA group (19.05 ng/ml; p< 0.001 for both). Serum adiponectin levels were significantly lower in the MetS-OA group than those in controls (8.09 vs. 10.07 μg/ml, respectively; p= 0.001). The synovium and IPFP in the MetS-OA group secreted more leptin and less adiponectin than those in the non-MetS-OA group (Leptin: 5.32 vs. 1.28 in synovium, respectively; p= 0.028; 6.44 vs. 0.88 in IPFP, respectively; p= 0.017. Adiponectin: 1.12 vs. 0.12 in synovium, respectively; p= 0.042; 1.07 vs. 0.09 in IPFP, respectively; p= 0.027). Resistin expression levels in the serum, SF, and articular tissues were similar among the groups.

Conclusions: Expressions of adipokines were different in the synovium and IPFP of OA patients with and without MetS.     

Inflammatory processes in obesity: focus on endothelial dysfunction and the role of adipokines as inflammatory mediators

Obesity predisposes the affected individuals to several metabolic, inflammatory, cardiovascular and malignant pathologies and is a top risk factor for premature mortality. It is now well known that inflammation has a major causative role in obesity-associated disease development and that obesity favors the establishment of a pro-inflammatory milieu at the level of adipose microenvironment. These inflammatory signals result in a disruption of normal cellular-crosstalk between adipose and non-adipose components leading to an altered metabolic and immunological status and a dysfunctional phenotype. Abnormal secretion of adipokines – small adipose-derived signaling molecules – can further assist in the inflammatory processes to offset the adipose tissue towards a dysfunctional state. Although adipokines have been recognized as the link between obesity and pathogenesis, studies are needed to fully understand their mechanism of action and underscore their therapeutic value. Here, we have reviewed obesity-induced metabolic and immunological changes at the level of vasculature and emphasize on the importance of adipokines, particularly leptin, vaspin and visfatin, for their therapeutic relevance.     

Maternal bisphenol a exposure during pregnancy and its association with adipokines in Mexican‐American children

Bisphenol A (BPA) is a high volume production chemical that has been detected in 93% of the United States population. It is thought to have endocrine disrupting activity but human data are limited. In this study, we examined whether prenatal or concurrent urinary BPA concentrations are associated with key metabolism‐related hormones, adiponectin and leptin (adipokines), in 9‐year‐old children. For this analysis, we used 188 mother‐child pairs from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) prospective study. BPA was measured in urinary spot samples during early (12.6 ± 3.9 weeks gestation) and late (26.3 ± 2.5 weeks gestation) pregnancy and in 9‐year‐old children. We found that BPA concentrations during late pregnancy were associated with increased plasma leptin in boys (β = 0.06, P = 0.01), controlling for maternal prepregnancy body mass index (BMI), pregnancy soda consumption, and smoking, years in US prior to pregnancy, maternal education, household poverty status, child BMI and child soda, fast food and sweet snack consumption at 9 years. Additionally, we found that BPA concentrations during early pregnancy are directly associated with plasma adiponectin levels in girls (β = 3.71, P = 0.03). However, we did not find any significant relationships between concurrent BPA concentrations and 9‐year child adiponectin or leptin. Overall, our data suggest that prenatal BPA concentrations may influence adipokine levels in 9‐year‐old children. Environ. Mol. Mutagen. 54:621–628, 2013. © 2013 Wiley Periodicals, Inc.     

The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity

Several adipose-derived cytokines (adipokines) have been suggested to act as a link between accumulated fat mass and altered insulin sensitivity. Resistin and tumour necrosis factor-alpha (TNF-alpha) have been implicated in impairing insulin sensitivity in rodents; conversely, two other adipokines, leptin and adiponectin, increase insulin sensitivity in lean and obese rodents. Currently, there is considerable focus on the concept that lipid accumulation in skeletal muscle leads to the development of insulin resistance. Adiponectin and leptin have each been demonstrated to increase rates of fatty acid (FA) oxidation and decrease muscle lipid content, which may in part be the underlying mechanism to their insulin sensitizing effect. These effects on FA metabolism appear to be mediated in part through the activation of AMP-activated protein kinase. Evidence derived from animal and human studies suggests that the ability of leptin and adiponectin to stimulate FA oxidation in muscle is impaired in the obese condition. Thus, leptin and adiponectin resistance may be an initiating factor in the accumulation of intramuscular lipids, such as diacylglycerol and ceramide, and the ensuing development of insulin resistance. Lifestyle factors such as diet and exercise are able to restore the sensitivity of muscle to leptin. The actual physiological roles of resistin and TNF-alpha in altering muscle lipid metabolism are more controversial, but each has been shown to directly impair insulin signalling and consequently, insulin stimulated glucose uptake in muscle. However, the possibility that resistin and TNF-alpha reduces insulin sensitivity in muscle by directly impairing FA metabolism in this tissue leading to lipid accumulation, has been virtually unexamined. Thus, the contribution of various adipokines to the development of insulin resistance is complex and not fully understood. Finally, the effects of these adipokines on metabolism and insulin sensitivity are generally studied in isolation, making it difficult to predict the interactive effects and the net impact on insulin sensitivity.