| Texto completo | |
| Autor(es): |
Moraes-Vieira, Pedro M.
[1, 2, 3, 4]
;
Yore, Mark M.
[1, 2, 5]
;
Sontheimer-Phelps, Alexandra
[1, 2, 6]
;
Castoldi, Angela
[1, 2]
;
Norseen, Julie
[1, 2]
;
Aryal, Pratik
[1, 2]
;
Sjoedin, Kotryna Simonyte
[1, 2, 7]
;
Kahn, Barbara B.
[1, 2]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [1] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, Boston, MA 02215 - USA
[2] Harvard Med Sch, Boston, MA 02215 - USA
[3] Univ Estadual Campinas, Dept Genet Evolut Microbiol & Immunol, Obes & Comorbid Res Ctr, Lab Immunometab, Inst Biol, BR-13083862 Campinas, SP - Brazil
[4] Univ Estadual Campinas, Div Metab, Expt Med Res Cluster, BR-13083862 Campinas, SP - Brazil
[5] Jounce Therapeut Inc, Cambridge, MA 02139 - USA
[6] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02215 - USA
[7] Umea Univ, Dept Clin Sci, Pediat, S-90187 Umea - Sweden
Número total de Afiliações: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 117, n. 49, p. 31309-31318, DEC 8 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
Adipose tissue (AT) inflammation contributes to systemic insulin resistance. In obesity and type 2 diabetes (T2D), retinol binding protein 4 (RBP4), the major retinol carrier in serum, is elevated in AT and has proinflammatory effects which are mediated partially through Toll-like receptor 4 (TLR4). We now show that RBP4 primes the NLRP3 inflammasome for interleukin-1 beta (IL1 beta) release, in a glucose-dependent manner, through the TLR4/MD2 receptor complex and TLR2. This impairs insulin signaling in adipocytes. IL1 beta is elevated in perigonadal white AT (PGWAT) of chow-fed RBP4-overexpressing mice and in serum and PGWAT of high-fat diet-fed RBP4-overexpressing mice vs. wild-type mice. Holo- or apo-RBP4 injection in wild-type mice causes insulin resistance and elevates PGWAT inflammatory markers, including IL1 beta. TLR4 inhibition in RBP4-overexpressing mice reduces PGWAT inflammation, including IL1 beta levels and improves insulin sensitivity. Thus, the proinflammatory effects of RBP4 require NLRP3-inflammasome priming. These studies may provide approaches to reduce AT inflammation and insulin resistance in obesity and diabetes. (AU) | |
| Processo FAPESP: | 15/15626-8 - Imunometabolismo em macrófagos e em linfócitos T nas doenças inflamatórias e metabólicas |
| Beneficiário: | Pedro Manoel Mendes de Moraes Vieira |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 14/02218-6 - Estudo das vias de sinalização induzidas por RBP4 em macrófagos e células dendríticas na resistência à insulina induzida pela obesidade |
| Beneficiário: | Angela Castoldi |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |