A feed-forward regulatory loop in adipose tissue promotes signaling by the hepatokine FGF21

Autor(es)

Han, Myoung Sook ^[1] ; Perry, Rachel J. ^{[2, 3]} ; Camporez, Joao-Paulo ^{[2, 4]} ; Scherer, Philipp E. ^{[5, 6, 7]} ; Shulman, Gerald I. ^{[2, 3]} ; Gao, Guangping ^[8] ; Davis, Roger J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 - USA

^[2] Yale Sch Med, Dept Internal Med, New Haven, CT 06520 - USA

^[3] Yale Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 - USA

^[4] Univ Sao Paulo, Dept Physiol, Ribeirao Preto Sch Med, BR-05508000 Sao Paulo - Brazil

^[5] Univ Texas Southwestern Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 - USA

^[6] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 - USA

^[7] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 - USA

^[8] Univ Massachusetts, Sch Med, Horae Gene Therapy Ctr, Worcester, MA 01605 - USA

• Tipo de documento: Artigo Científico
• Fonte: GENES & DEVELOPMENT; v. 35, n. 1-2, p. 133-146, JAN 1 2021.
• Citações Web of Science: 0

Resumo

The cJun NH2-terminal kinase (JNK) signaling pathway is activated by metabolic stress and promotes the development of metabolic syndrome, including hyperglycemia, hyperlipidemia, and insulin resistance. This integrated physiological response involves cross-talk between different organs. Here we demonstrate that JNK signaling in adipocytes causes an increased circulating concentration of the hepatokine fibroblast growth factor 21 (FGF21) that regulates systemic metabolism. The mechanism of organ crosstalk is mediated by a feed-forward regulatory loop caused by JNK-regulated FGF21 autocrine signaling in adipocytes that promotes increased expression of the adipokine adiponectin and subsequent hepatic expression of the hormone FGF21. The mechanism of organ cross-talk places circulating adiponectin downstream of autocrine FGF21 expressed by adipocytes and upstream of endocrine FGF21 expressed by hepatocytes. This regulatory loop represents a novel signaling paradigm that connects autocrine and endocrine signaling modes of the same hormone in different tissues. (AU)

• Processo FAPESP: 18/04956-5 - Impacto do receptor de estrogênio alpha na Doença Hepática Gordurosa não Alcoólica e metabolismo energético do fígado
• Beneficiário: João Paulo Gabriel Camporez
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores