Activation of non-canonical WNT signaling in human visceral adipose tissue contributes to local and systemic inflammation.

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 ac...

ver descrição completa

Detalhes bibliográficos
Autores: Zuriaga, María A, Fuster, José J, Farb, Melissa G, MacLauchlan, Susan, Bretón-Romero, Rosa, Karki, Shakun, Hess, Donald T, Apovian, Caroline M, Hamburg, Naomi M, Gokce, Noyan, Walsh, Kenneth
Tipo de documento: artigo
Data de publicação:2017
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17484
Acesso em linha:http://hdl.handle.net/20.500.12105/17484
Access Level:Acceso aberto
Palavra-chave:Gene Expression Regulation
Wnt Signaling Pathway
Adult
Female
Humans
Inflammation
Male
Panniculitis
Subcutaneous Fat
Descrição
Resumo: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.

Registros relacionados