Publicação

Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity

Detalhes bibliográficos
Resumo:	Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.
Autores principais:	Seo, Ji A.
Outros Autores:	Kang, Min Cheol; Yang, Won Mo; Hwang, Won Min; Kim, Sang Soo; Hong, Soo Hyun; Heo, Jee In; Vijyakumar, Achana; Pereira de Moura, Leandro; Uner, Aykut; Huang, Hu; Lee, Seung Hwan; Lima, Inês S.; Park, Kyong Soo; Kim, Min Seon; Dagon, Yossi; Willnow, Thomas E.; Aroda, Vanita; Ciaraldi, Theodore P.; Henry, Robert R.; Kim, Young Bum
Assunto:	General Chemistry General Biochemistry,Genetics and Molecular Biology General Physics and Astronomy
Ano:	2020
País:	Portugal
Tipo de documento:	artigo
Tipo de acesso:	acesso aberto
Instituição associada:	Universidade Nova de Lisboa
Idioma:	inglês
Origem:	Repositório Institucional da UNL

Descrição
Resumo:	Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.