Activation of non-canonical WNT signaling in human visceral adipose tissue contributes to local and systemic inflammation.
Activation of non-canonical WNT signaling in human visceral adipose tissue contributes to local and systemic inflammation.
复制标题
DOI：
10.1038/s41598-017-17509-5
复制
发表时间：
2017-12-11
影响因子：
4.6
通讯作者：
Walsh K
中科院分区：
文献类型：
--
作者：
Zuriaga MA;Fuster JJ;Farb MG;MacLauchlan S;Bretón-Romero R;Karki S;Hess DT;Apovian CM;Hamburg NM;Gokce N;Walsh K
内脏脂肪的积累与全身炎症和增加的心脏代谢风险密切相关。WNT5A是一种非规范的WNT配体，在动物研究中已被证明可促进脂肪组织炎症和胰岛素抵抗。在其他非规范通路中，WNT5A激活平面细胞极性（PCP）信号。目前的研究调查了非规范WNT5A/PCP信号对肥胖个体内脏脂肪组织（VAT）炎症和相关代谢功能障碍的潜在贡献。采用qRT-PCR方法分析接受减肥手术受试者的VAT和皮下脂肪组织（SAT）样本中WNT/PCP基因的表达。体外实验采用VAT和SAT活检分离的前脂肪细胞进行。与SAT相比，33个PCP基因中有23个在VAT中表达丰富。在VAT中观察到个体PCP基因的强正表达相关性。WNT5A在VAT中的表达与JNK信号活性、il - 6、腰臀比、hsCRP等指标相关，而在SAT中不存在。体外实验中，WNT5A可促进人前脂肪细胞中il - 6的表达。综上所述，VAT中非规范WNT5A信号的升高导致了该储库中IL-6产生的加剧，以及通常与内脏肥胖相关的低级别全身性炎症。
The accumulation of visceral adiposity is strongly associated with systemic inflammation and increased cardiometabolic risk. WNT5A, a non-canonical WNT ligand, has been shown to promote adipose tissue inflammation and insulin resistance in animal studies. Among other non-canonical pathways, WNT5A activates planar cell polarity (PCP) signaling. The current study investigated the potential contribution of non-canonical WNT5A/PCP signaling to visceral adipose tissue (VAT) inflammation and associated metabolic dysfunction in individuals with obesity. VAT and subcutaneous adipose tissue (SAT) samples obtained from subjects undergoing bariatric surgery were analyzed by qRT-PCR for expression of WNT/PCP genes. In vitro experiments were conducted with preadipocytes isolated from VAT and SAT biopsies. The expression of 23 out of 33 PCP genes was enriched in VAT compared to SAT. Strong positive expression correlations of individual PCP genes were observed in VAT. WNT5A expression in VAT, but not in SAT, correlated with indexes of JNK signaling activity, IL6, waist-to-hip ratio and hsCRP. In vitro, WNT5A promoted the expression of IL6 in human preadipocytes. In conclusion, elevated non-canonical WNT5A signaling in VAT contributes to the exacerbated IL-6 production in this depot and the low-grade systemic inflammation typically associated with visceral adiposity.
登录
查看更多内容
影响因子：
10.9
作者：
Christodoulides, Constantinos;Lagathu, Claire;Sethi, Jaswinder K.;Vidal-Puig, Antonio
通讯作者：
Vidal-Puig, Antonio
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0601752103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Gesta, S;Blüher, M;Kahn, CR
通讯作者：
Kahn, CR
影响因子：
5.8
作者：
Bastard, JP;Jardel, C;Hainque, B
通讯作者：
Hainque, B
影响因子：
4.8
作者：
Fain, JN;Madan, AK;Bahouth, SW
通讯作者：
Bahouth, SW