脂联素在衰老和损伤中成骨作用的研究进展及主要困惑探讨

脂肪因子脂联素与骨代谢关系密切,并进行了大量的细胞、模型动物及人群的调查研究。虽然许多研究证实了脂联素对成骨的正向调节作用,但是研究结果不完全一致。目前仍未能完全了解脂联素信号通路在年龄、疾病及骨修复中的重要性。该述评探讨了脂联素对成骨作用的初步研究结论,脂联素不同异构体、不同受体的可能作用通路,以及老年人群的脂联素生物学改变。探究脂联素对骨骼生物学的调控作用有助于药物开发和非药物（生活方式）干预方式的研究。针对脂联素信号进行干预,可能有助于维护衰老过程中的骨健康和损伤后的骨骼修复。     

HDL2-cholesterol/HDL3-cholesterol ratio was associated with insulin resistance,high-molecular-weight adiponectin,and components for metabolic syndrome in Japanese

AimsRecent data have suggested a relationship between the high-density lipoprotein (HDL) subclass ratio and metabolic syndrome (MetS). However, limited information is available regarding the relationships between the HDL subclass ratio and insulin resistance, associated adipocytokine levels, and MetS components. The associations of the high-density lipoprotein 2 cholesterol (HDL₂-C) to high-density lipoprotein 3 cholesterol (HDL₃-C) ratio with the homeostasis model assessment of insulin resistance (HOMA-IR) index, high-molecular-weight adiponectin (HMW-Ad) levels, and MetS components were examined.MethodsThe study included 1155 Japanese subjects who met our inclusion criteria and underwent an annual health examination that included an HDL subclass analysis.ResultsThe HDL₂-C/HDL₃-C ratio and the HMW-Ad level gradually decreased as the number of MetS components increased. In contrast, HOMA-IR gradually increased as the number of MetS components increased. The HDL₂-C/HDL₃-C ratio correlated inversely with HOMA-IR and positively with the HMW-Ad level. A strong positive correlation was observed between the HDL₂-C/HDL₃-C ratio and the HDL-C level. The HDL₂-C/HDL₃-C ratio exhibited moderate negative correlations with the body mass index, waist circumference, and triglyceride level. Weak negative correlations were observed for the HDL₂-C/HDL₃-C ratio with the systolic and diastolic blood pressure and fasting plasma glucose levels.ConclusionsOur data indicated that the HDL₂-C/HDL₃-C ratio was associated with insulin resistance, the HMW-Ad level, and MetS components, and it was useful for evaluating MetS in Japanese individuals.     

老年高血压患者颈动脉粥样硬化与血清脂联素、抵抗素水平的相关性

 目的 研究老年高血压患者颈动脉粥样硬化程度、血清中的脂联素、抵抗素水平的相关性。方法 选择2016-01至2017-12解放军总医院第三医学中心收治的老年高血压患者112例,所有患者均行颈部血管超声检查,根据颈动脉内中膜厚度将所有患者分为正常组32例,内中膜增厚组42例和斑块组38例,测定各组患者血清脂联素、抵抗素水平,之后进行对比分析及相关分析。结果 血清脂联素水平和颈动脉内中膜厚度呈负相关(r=-0.562),抵抗素水平和颈动脉内中膜厚度呈正相关(r=0.621),胰岛素抵抗、血清抵抗素水平是颈动脉粥样硬化的独立危险因素,血清脂联素水平是动脉粥样硬化的保护因素。结论 对于老年高血压患者早期监测脂联素和抵抗素水平的变化有助于监测颈动脉粥样硬化的发生发展。     

脂肪细胞因子在2型糖尿病并发大血管病变中的意义

目的:探讨血清脂联素(APN)及视黄醇结合蛋白4(RBP4)水平在2型糖尿病(T2DM)大血管病变中的变化及意义。方法:选取T2DM并发大血管病变者36例(Ⅰ组)、单纯T2DM者38例(Ⅱ组)和健康体检者32例(Ⅲ组),采用ELISA法检测其血清标本的APN和RBP4浓度,同时检测血糖血脂及糖化血红蛋白(HbA1c)浓度。结果:Ⅰ组血清APN的浓度为(3.5±0.8)mg/L,显著低于Ⅱ组(7.8±0.9)mg/L和Ⅲ组(11.6±1.6)mg/L;Ⅰ组血清RBP4浓度为(23.1±2.8)mg/L,显著高于Ⅱ组(13.6±1.5)mg/L和Ⅲ组(10.2±1.7)mg/L。APN浓度与空腹血糖、甘油三酯、低密度脂蛋白胆固醇和HbA1c水平呈负相关(r=-0.402、-0.322、-0.316、-0.518和-0.469,均P0.05);而RBP4与上述指标呈正相关(r=0.486、0.347、0.396、0.401和0.355,均P0.05),与高密度脂蛋白胆固醇呈负相关(r=-0.426,P0.05)。结论:血清ANP和RBP4检测对T2DM大血管病变具有重要的预测价值。     

Effect of methylphenidate treatment on appetite and levels of leptin,ghrelin, adiponectin,and brain-derived neurotrophic factor in children and adolescents with attention deficit and hyperactivity disorder

Objectives. We aimed to explore whether the use of methylphenidate relates leptin, ghrelin, adiponectin, and brain-derived neurotrophic factor (BDNF). In addition, the relationship between methylphenidate-related weight loss in attention deficit hyperactivity disorder (ADHD) patients and these biomolecules were evaluated. Methods. Thirty ADHD patients receiving methylphenidate and 20 healthy controls were included. Leptin, ghrelin, adiponectin, and BDNF levels were measured at baseline and after two-month treatment in both groups. Results. At baseline, leptin, ghrelin, adiponectin, and BDNF levels were similar in the ADHD and control groups. The most common adverse events occurring in the ADHD group after a 2-month treatment period included loss of appetite (70%) and weight loss (66.7%). A significant difference was found in body weight, BMI, and CGI scores of the ADHD patients after the treatment. While post-treatment ghrelin and adiponectin levels were significantly higher in the ADHD group, BDNF level was significantly lower. Post-treatment decrease in leptin levels was not significant. Conclusions. Leptin and BDNF were not associated with poor appetite and/or weight loss due to methylphenidate treatment. However, ghrelin and adiponectin might be biomolecules that play a role in underlying neurobiological mechanisms of methylphenidate-related appetite or weight loss.     

Changes of adiponectin and its receptors in rats following chronic renal failure

Objective: To investigate changes of adiponectin and its receptors (Adipo R) in rats following chronic renal failure. Methods: Male SD rats were randomly divided into two groups: control group and chronic renal failure (CRF) group. The CRF group were gavaged with adenine (300?mg/kg/d) for 4 weeks and the control group with drinking water. All rats were anesthetized at 2nd or 4th week and blood and urine samples were collected for detection of renal function, 24?h urine protein and adiponectin concentration. Renal tissues were also collected for HE staining, immunohistochemistry and RT-PCR screening. Results: Compared with control group, the serum concentrations of urea and creatinine, 24?h urine protein excretion in the CRF group were significantly higher at 2nd week and further increased at 4th week (p?0.05). The adiponectin levels in serum and urine in the CRF group were significantly higher than those of control group (p?0.01). The renal expressions of Adipo R1 and Adipo R2 in CRF group were also significantly increased compared to control group (p?0.01). The increased expressions of Adipo R1 and Adipo R2 were positively related to the adiponectin levels in serum, urine, and 24?h urine protein. Conclusion: The significant changes in expression of adiponectin and its receptors in rat CRF model could be an adaptive response that may provide the basis to understand pathological changes in chronic kidney disease.     

Soy β-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats

Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate–activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.     

缺氧缺血性脑病新生儿脂联素、胰岛素样生长因子-1的变化

目的探讨缺氧缺血性脑病(HIE)新生儿血清胰岛素样生长因子-1(IGF-1)、脂联素(APN)水平的变化。方法选择足月HIE新生儿52例(重度HIE组15例,中度HIE组20例,轻度HIE组17例),测定脐血及生后3~5 d(HIE急性期)、10~14 d(HIE恢复期)的血清IGF-1、APN水平;另选同期出生的20例足月健康新生儿作为对照组。结果轻、中、重度HIE组及对照组四组间脐血及生后3~5 d时APN、IGF-1水平的差异有统计学意义(P均0.01),均随HIE程度加重而下降,两两比较差异有统计学意义(P均0.05);HIE恢复期新生儿APN、IGF-1水平显著增加,但APN水平中度HIE组和重度HIE组仍低于对照组,差异有统计学意义(P均0.05);重度HIE组IGF-1仍低于对照组,差异有统计学意义(P0.05);HIE患儿脐血、急性期血清IGF-1、APN水平呈显著正相关(r=0.53、0.61,P均0.01)。结论 HIE患儿血清IGF-1、APN水平降低与HIE的病理生理过程密切相关,可作为病情程度的判断指标之一,对临床诊断及预后的判断具有指导意义。