Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects.
Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects.
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DOI：
10.1371/journal.pone.0032437
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Laudes M
中科院分区：
文献类型：
--
作者：
Schulte DM;Müller N;Neumann K;Oberhäuser F;Faust M;Güdelhöfer H;Brandt B;Krone W;Laudes M
肥胖与脂肪组织中的巨噬细胞渗透有关。这些炎症细胞不仅通过经典的细胞因子影响脂肪细胞，而且还通过分泌的糖肽Wnt5A影响脂肪细胞。健康的脂肪细胞能够释放Wnt5A抑制物sFRP5。然而，这种保护作用在肥胖症中被发现减弱。本研究的目的是研究(1)肥胖受试者是否表现出血清Wnt5A浓度的升高；(2)限制热量摄入是否会影响肥胖受试者的Wnt5A和/或sFRP5血清浓度。23例肥胖者(BMI 44.1±1.1 kg/m2)和12例年龄和性别匹配的瘦对照组(BMI 22.3±0.4 kg/m2)被纳入研究。肥胖者接受为期12周的低卡路里饮食(约800千卡/天)治疗。用阻抗法评价体成分，用HOMA-IR法评价胰岛素敏感性，用ELISA法测定瘦素/脂联素比值和血清Wnt5A、sFRP5浓度。免疫组织化学方法进一步从蛋白水平检测sFRP5在人脂肪组织中的表达。在任何瘦身对照受试者的血清样本中均未检测到促炎性Wnt5A。然而，在肥胖症患者中，Wnt5A与这些受试者的低级别炎症显著一致。限制热量摄入使肥胖患者体重从131.9±4.0 kg下降到112.3±3.2 kg。伴随而来的是HOMA-IR和瘦素/脂联素比率的显著下降，表明胰岛素敏感性有所改善。有趣的是，这些代谢的改善与血清抗炎因子和Wnt5A抑制物sFRP5浓度的显著增加有关。肥胖与人类血清促炎因子Wnt5A水平升高有关。此外，限制热量摄入有益于影响这些受试者血清中抗炎sFRP5的浓度。这些发现提示了一种新的肥胖低度炎症调节系统，营养疗法可以影响这种调节系统。
Obesity is associated with macrophage infiltration of adipose tissue. These inflammatory cells affect adipocytes not only by classical cytokines but also by the secreted glycopeptide wnt5a. Healthy adipocytes are able to release the wnt5a inhibitor sFRP5. This protective effect, however, was found to be diminished in obesity. The aim of the present study was to examine (1) whether obese human subjects exhibit increased serum concentrations of wnt5a and (2) whether wnt5a and/or sFRP5 serum concentrations in obese subjects can be influenced by caloric restriction. 23 obese human subjects (BMI 44.1±1.1 kg/m2) and 12 age- and sex-matched lean controls (BMI 22.3±0.4 kg/m2) were included in the study. Obese subjects were treated with a very low-calorie diet (approximately 800 kcal/d) for 12 weeks. Body composition was assessed by impedance analysis, insulin sensitivity was estimated by HOMA-IR and the leptin-to-adiponectin ratio and wnt5a and sFRP5 serum concentrations were measured by ELISA. sFRP5 expression in human adipose tissue biopsies was further determined on protein level by immunohistology. Pro-inflammatory wnt5a was not measurable in any serum sample of lean control subjects. In patients with obesity, however, wnt5a became significantly detectable consistent with low grade inflammation in such subjects. Caloric restriction resulted in a weight loss from 131.9±4.0 to 112.3±3.2 kg in the obese patients group. This was accompanied by a significant decrease of HOMA-IR and leptin-to-adiponectin ratio, indicating improved insulin sensitivity. Interestingly, these metabolic improvements were associated with a significant increase in serum concentrations of the anti-inflammatory factor and wnt5a-inhibitor sFRP5. Obesity is associated with elevated serum levels of pro-inflammatory wnt5a in humans. Furthermore, caloric restriction beneficially affects serum concentrations of anti-inflammatory sFRP5 in such subjects. These findings suggest a novel regulatory system in low grade inflammation in obesity, which can be influenced by nutritional therapy.
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影响因子：
4.8
作者：
Bilkovski, Roman;Schulte, Dominik M.;Laudes, Matthias
通讯作者：
Laudes, Matthias
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影响因子：
3.7
作者：
Schultz O;Oberhauser F;Saech J;Rubbert-Roth A;Hahn M;Krone W;Laudes M
通讯作者：
Laudes M
影响因子：
64.8
作者：
Takemaru, KI;Yamaguchi, S;Moon, RT
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Moon, RT
影响因子：
7.7
作者：
Schertzer JD;Tamrakar AK;Magalhães JG;Pereira S;Bilan PJ;Fullerton MD;Liu Z;Steinberg GR;Giacca A;Philpott DJ;Klip A
通讯作者：
Klip A
影响因子：
7.7
作者：
Lagathu, Claire;Christodoulides, Constantinos;Virtue, Sam;Cawthorn, William P.;Franzin, Chiara;Kimber, Wendy A.;Nora, Edoardo Dalla;Campbell, Mark;Medina-Gomez, Gema;Cheyette, Benjamin N. R.;Vidal-Puig, Antonio J.;Sethi, Jaswinder K.
通讯作者：
Sethi, Jaswinder K.