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

Author(s):Show less -

Seo, Ji A. ^{[1, 2, 3]} ; Kang, Min-Cheol ^{[1, 2, 4]} ; Yang, Won-Mo ^{[1, 2, 5]} ; Hwang, Won Min ^{[1, 2, 6]} ; Kim, Sang Soo ^{[1, 2, 7, 8]} ; Hong, Soo Hyun ^{[1, 9, 2]} ; Heo, Jee-In ^[3] ; Vijyakumar, Achana ^{[1, 2]} ; de Moura, Leandro Pereira ^{[10, 1, 2]} ; Uner, Aykut ^{[1, 2]} ; Huang, Hu ^{[1, 2, 11]} ; Lee, Seung Hwan ^{[1, 2, 12]} ; Lima, Ines S. ^{[1, 2, 13]} ; Park, Kyong Soo ^[5] ; Kim, Min Seon ^[14] ; Dagon, Yossi ^{[1, 2]} ; Willnow, Thomas E. ^[15] ; Aroda, Vanita ^{[16, 1, 17, 18]} ; Ciaraldi, Theodore P. ^{[16, 18]} ; Henry, Robert R. ^{[16, 18]} ; Kim, Young-Bum ^{[1, 2]}

Affiliation:Show less -

^[1] Harvard Med Sch, Boston, MA 02115 - USA

^[2] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 - USA

^[3] Korea Univ, Coll Med, Div Endocrinol, Dept Internal Med, Seoul - South Korea

^[4] Korea Food Res Inst, Res Grp Food Proc, Jeollabuk Do - South Korea

^[5] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul - South Korea

^[6] Konyang Univ, Div Nephrol, Dept Internal Med, Coll Med, Daejeon - South Korea

^[7] Pusan Natl Univ Hosp, Dept Internal Med, Busan - South Korea

^[8] Pusan Natl Univ Hosp, Biomed Res Inst, Busan - South Korea

^[9] Columbia Univ, New York, NY - USA

^[10] Univ Estadual Campinas, Sch Appl Sci, Limeira - Brazil

^[11] East Carolina Univ, East Carolina Diabet & Obes Inst, Greenville, NC 27858 - USA

^[12] Catholic Univ Korea, Coll Med, Seoul - South Korea

^[13] Univ Nova Lisboa, Lisbon - Portugal

^[14] Univ Ulsan, Dept Internal Med, Coll Med, Asan Med Ctr, Seoul - South Korea

^[15] Max Delbrueck Ctr Mol Med, Mol Cardiovasc Res, Berlin - Germany

^[16] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 - USA

^[17] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 - USA

^[18] Vet Affairs San Diego Healthcare Syst 9111 G, San Diego, CA 92161 - USA

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 11, n. 1 APR 24 2020.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 13/14149-6 - Physiological role of ROCK1 in glucose homeostasis
• Grantee: Leandro Pereira de Moura
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate