Serum soluble receptor for advanced glycation end products correlates inversely with measures of adiposity in young adults

Advanced glycation end products (AGEs) may promote inflammation by interacting with the receptor for advanced glycation end products. Serum soluble receptor for advanced glycation end products (sRAGE), a form of receptor for advanced glycation end products thought to mediate AGE’s inflammatory properties, is decreased in diabetes mellitus and coronary artery disease. Evidence in older adults suggests that sRAGE is depressed in individuals without current disease who are obese; however, 2 studies have failed to find this correlation. We hypothesized that sRAGE would be inversely correlated with adiposity and positively correlated with inflammation, even in apparently healthy, young adults. By considering adults of body mass index (BMI) varying from normal weight to overweight and obese, we aimed to define how closely AGEs and sRAGE correlate with adiposity and other indicators of metabolic stress. Anthropometric measurements and fasting blood samples were obtained from participants (n = 69). Sera were analyzed for sRAGE, n-epsilon carboxy-methyl-lysine, a measure of AGEs, and high sensitivity C-reactive protein. High molecular weight adiponectin, glucose, insulin, total cholesterol, high-density lipoprotein, and triacylglycerol were also assessed (n = 32). Spearman rank correlations were used to evaluate the relationship among indicators of adiposity and biochemical indicators of metabolic health and inflammation. Factors inversely correlated with sRAGE include weight (R_s = −0.397; P = .001), waist circumference (−0.291; P = .015), and BMI (−0.3338; P = .004). High molecular weight adiponectin was positively correlated with sRAGE, and predictors of sRAGE included BMI and total cholesterol. This is the first time these associations have been found in a diverse population of young adults.     

Circulating adiponectin levels are associated with peak oxygen uptake in Japanese

Objective

The aim of this study was to investigate the link between circulating adiponectin levels and peak oxygen uptake and/or physical activity in Japanese.

Methods

A total of 528 subjects (188 men and 340 women) were enrolled in this cross-sectional study. Circulating adiponectin levels, physical activity measured by tri-axial accelerometers, peak oxygen uptake and metabolic risk parameters were evaluated. We also assessed anthropometric factors, blood pressure, blood examinations and energy intake.

Results

Circulating adiponectin levels were 6.7 ± 3.0 μg/mL in men and 11.0 ± 4.9 μg/mL in women. Circulating adiponectin levels were positively correlated with physical fitness after adjusting for age, physical activity evaluated by Σ [metabolic equivalents × h per week (METs h/w)], cigarette smoking habit and energy intake in both sexes. However, these associations were attenuated further after adjusting for body mass index including other confounding factors, especially in men. However, circulating adiponectin levels were not associated with physical activity in either sex.

Conclusion

Circulating adiponectin levels were associated with peak oxygen uptake rather than physical activity.     

妊娠期糖尿病患者和正常孕妇的内脏脂肪素、脂联素在不同孕周的血清及新生儿脐血清中的表达

目的：研究妊娠期糖尿病患者和正常孕妇的内脏脂肪素、脂联素在不同孕周的血清及新生儿脐血清中的表达。方法：2013年1月-7月在青岛市立医院产科产检的孕妇中,选取妊娠期糖尿病孕妇62例为试验组,正常孕妇68例为对照组。用ELISA方法检测31~33周孕妇血清,37~41周孕妇血清,足月新生儿脐血血清脂联素（adiponectin）、内脂素（visfatin）的含量。结果：随着妊娠的进展,血清脂联素水平呈逐渐下降,内脂素水平逐渐上升,三个采血时间段比较差异均有统计学意义（P＆lt;0.001）。妊娠期糖尿病患者血清脂联素水平在中孕及晚孕均低于正常妊娠组,而血清内脂素水平在中孕及晚孕均高于正常妊娠组,两组比较差异均有统计学意义（P＆lt;0.001）。新生儿脐血脂联素、内脂素水平显著高于母血,比较差异均有统计学意义（P＆lt;0.001）。结论：可考虑应用血清脂联素水平与内脂素水平对妊娠期糖尿病进行预测及评估,并作为指导GDM的治疗的新的理论。     

Serum adiponectin levels predict the effect of short-term dietary interventions on insulin sensitivity in humans

Aims/hypothesis Fat-rich diets can acutely induce insulin resistance. Data from adiponectin knock-out mice suggest that this effect might be increased in the absence of adiponectin. In the present study we tested whether plasma adiponectin concentrations influence changes in insulin sensitivity induced by a short-term dietary intervention in humans.Methods We analysed data from 27 healthy, non-obese men with normal glucose tolerance. These men ate a diet high in fat and a diet high in carbohydrates for three days each.Results The high-fat diet induced a significant drop in insulin sensitivity (determined by euglycaemic–hyperinsulinaemic clamp) compared to baseline (0.100±0.009 vs 0.083±0.007 µmol·kg^–1·min^–1·(pmol·l^–1), p=0.01). The drop in insulin sensitivity was more pronounced in subjects with low serum adiponectin (0.094±0.011 vs 0.077±0.010 µmol·kg^–1·min^–1·(pmol·l^–1), p=0.02) than in subjects with high serum adiponectin (0.103±0.011 vs 0.090±0.040 µmol·kg^–1·min^–1·(pmol·l^–1), p=0.16). In the whole group the high-carbohydrate, low-fat diet did not cause an increase in insulin sensitivity (0.095±0.007 vs 0.102±0.009 µmol·kg^–1·min^–1·(pmol·l^–1), p=0.06). However, insulin sensitivity was significantly increased in the subgroup with low serum adiponectin levels (0.084±0.013 vs 0.099±0.018 µmol·kg^–1·min^–1·(pmol·l^–1), p=0.01). In an additional multivariate analysis post-intervention insulin sensitivity was predicted by pre-intervention insulin sensitivity (p<0.001) and adiponectin concentrations (p=0.001).Conclusions/interpretation These data indicate that the reduction in insulin sensitivity achieved by a short-term high-fat diet is more pronounced in non-obese subjects with low serum adiponectin. Thus it is possible that the restriction of dietary fat and a diet high in carbohydrates might be particularly effective in subjects with low adiponectin such as obese or Type 2 diabetic individuals.     

Regulatory Role of Autophagy in Globular Adiponectin-Induced Apoptosis in Cancer Cells

Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.     

非酒精性脂肪性肝病患者血清脂联素与胰岛素表达水平及其相关性研究

目的 探讨非酒精性脂肪性肝病患者血清脂联素与胰岛素表达水平及其相关性.方法 选择2010年1月至2011年1月自贡市仁济医学中心收治的非酒精性脂肪性肝病患者50例为观察组,同时收集健康志愿者40例为对照组.用酶联免疫吸附测定法检测2组空腹及餐后2h血清脂联素水平,用化学发光法检测空腹及餐后2h胰岛素表达水平,并进行相关性分析.结果 观察组和正常对照组空腹脂联素水平分别为（912 ±29）、（1 033±53）μg/L,组间差异有统计学意义（P＜0.05）;空腹胰岛素水平分别为（13.8±1.0）、（7.3±1.0）mU/L,组间差异有统计学意义（P＜0.01）.观察组和正常对照组餐后2h脂联素水平分别为（854 ±38）、（1 010±48）μg/L,组间差异有统计学意义（P＜0.05）;餐后2h胰岛素水平分别为（112 ±23）、（28 ±3） μg/L,组间差异有统计学意义（P＜0.01）.相关性分析显示,非酒精性脂肪性肝病患者空腹及餐后2h脂联素与胰岛素水平均呈负相关（空腹：r=-0.328,P=0.020;餐后2 h：r=-0.391,P =0.005）.结论 非酒精性脂肪性肝病进展的同时伴随着胰岛素及脂联素水平的变化,二者呈负相关,这种负相关可能以餐后2h更明显.     

血管外膜脂肪组织源性脂联素通过磷脂酰肌醇-3-激酶/蛋白激酶B信号通路促进血管内膜损伤后内皮细胞增生的研究

目的 研究血管外膜脂肪组织分泌的脂联素对血管内膜损伤后内皮细胞增生的影响及可能的分子机制.方法 将C57BL/6J野生型小鼠72只完全随机分为A组（仅剪开颈部皮肤后再缝合）、B组（给予颈动脉套管结扎）、C组（剪开颈部皮肤后于颈动脉周围移植脂联素基因敲除小鼠脂肪组织）及D组（颈动脉套管结扎同时于颈动脉周围移植脂联素基因敲除小鼠脂肪组织）,每组18只.手术8周后处死小鼠,取各组小鼠左颈总动脉切片,采用苏木精-伊红染色,观察各组小鼠颈动脉内膜增生情况并测定内膜增厚程度,以内膜面积与中膜面积的比值表示.应用酶联免疫吸附试验检测各组小鼠颈动脉组织内脂联素水平.采用蛋白质印迹法检测各组小鼠颈动脉组织内磷脂酰肌醇-3-激酶（PI3K）、蛋白激酶B（AKT）及其磷酸化产物的水平.体外实验将小鼠内皮细胞以5＆#215;104个/ml接种于内皮细胞生长培养基中,将细胞分为对照组、脂联素组（在对照组基础上加入重组脂联素100 mg/L）及PI3K抑制组（在对照组基础上加入重组脂联素100 mg/L和PI3K抑制剂LY29400 250 μg/L）,利用标记5-溴脱氧尿嘧啶核苷（BrdU）的微小RNA（miR-21）模拟物转染小鼠内皮细胞,使其在细胞中呈过表达状态,通过荧光显微镜观察各组内皮细胞的增生情况,比较BrdU阳性细胞百分率.结果 B组小鼠颈动脉内膜增厚程度明显大于A组、C组和D组,差异均有统计学意义[（1.37±0.09）比（0.82±0.18）、（0.71±0.05）、（1.03±0.06）,P值分别为0.023、0.001、0.010].B组小鼠脂联素的表达水平明显高于A组、C组和D组,差异有统计学意义[（95±6） ng/L比（77±5）ng/L、（55±5）ng/L、（70±7）ng/L,P=0.049、0.021、0.027].C组与D组小鼠颈动脉组织内AKT及PI3K磷酸化产物水平较A组与B组降低.体外实验脂联素组内皮细胞的BrdU阳性细胞率较对照组明显增加,差异有统计学意?     

脂联素基因多态性与2型糖尿病的相关性

脂联素是新近发现由脂肪组织特异性分泌的蛋白质,由人类脂联素基因(APM-1/ACDC/ADIPOQ)编码.目前许多研究表明脂联素基因多态性与2型糖尿病和胰岛素抵抗相关,且受遗传背景和环境因素影响,不同群体研究结果之间存在差异.同时,脂联素基因多态性与2型糖尿病的治疗和干预也存在相关性.     

Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells

Aims/hypothesis The aim of this study was to determine whether adiponectin elicits glucose uptake via increased GLUT4 translocation and to investigate the metabolic fate of glucose in skeletal muscle cells treated with globular adiponectin.Materials and methods Basal and insulin-stimulated 2-deoxy-d-[³H]glucose uptake, cell surface myc-tagged GLUT4 content, production of ¹⁴CO₂ by oxidation of d-[U-¹⁴C]glucose and [1-¹⁴C]oleate, and incorporation of d-[U-¹⁴C]glucose into glycogen and lactate were measured in the presence and absence of globular adiponectin.Results RT-PCR and Western blot analysis revealed that L6 cells and rat skeletal muscle cells express AdipoR1 mRNA and protein. Globular adiponectin increased both GLUT4 translocation and glucose uptake by increasing the transport V_max of glucose without altering the K_m. Interestingly, the incorporation of d-[U-¹⁴C]glucose into glycogen under basal and insulin-stimulated conditions was significantly decreased by globular adiponectin, whereas lactate production was increased. Furthermore, globular adiponectin did not affect glucose oxidation, but enhanced phosphorylation of AMP kinase and acetyl-CoA carboxylase, and fatty acid oxidation.Conclusions/interpretation The present study is the first to show that globular adiponectin increases glucose uptake in skeletal muscle cells via GLUT4 translocation and subsequently reduces the rate of glycogen synthesis and shifts glucose metabolism toward lactate production. These effects are consistent with the increased phosphorylation of AMP kinase and acetyl-CoA carboxylase and oxidation of fatty acids induced by globular adiponectin.