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Gutierrez 2022 Cell Rep Med

From Bioblast
Publications in the MiPMap
Gutierrez AD, Gao Z, Hamidi V, Zhu L, Saint Andre KB, Riggs K, Ruscheinsky M, Wang H, Yu Y, Miller C 3rd, Vasquez H, Taegtmeyer H, Kolonin MG (2022) Anti-diabetic effects of GLP1 analogs are mediated by thermogenic interleukin-6 signaling in adipocytes. https://doi.org/10.1016/j.xcrm.2022.100813

Β» Cell Rep Med 3:100813. PMID: 36384099 Open Access

Gutierrez Absalon D, Gao Zhanguo, Hamidi Vala, Zhu Liang, Bermudez Saint Andre Karla, Riggs Kayla, Ruscheinsky Monika, Wang Hongyu, Yu Yongmei, Miller Charles 3rd, Vasquez Hernan, Taegtmeyer Heinrich, Kolonin Mikhail G (2022) Cell Rep Med

Abstract: Mechanisms underlying anti-diabetic effects of GLP1 analogs remain incompletely understood. We observed that in prediabetic humans exenatide treatment acutely induces interleukin-6 (IL-6) secretion by monocytes and IL-6 in systemic circulation. We hypothesized that GLP1 analogs signal through IL-6 in adipose tissue (AT) and used the mouse model to test if IL-6 receptor (IL-6R) signaling underlies the effects of the GLP1-IL-6 axis. We show that liraglutide transiently increases IL-6 in mouse circulation and IL-6R signaling in AT. Metronomic liraglutide treatment resulted in AT browning and thermogenesis linked with STAT3 activation. IL-6-blocking antibody treatment inhibited STAT3 activation in AT and suppressed liraglutide-induced increase in thermogenesis and glucose utilization. We show that adipose IL-6R knockout mice still display liraglutide-induced weight loss but lack thermogenic adipocyte browning and metabolism activation. We conclude that the anti-diabetic effects of GLP1 analogs are mediated by transient upregulation of IL-6, which activates canonical IL-6R signaling and thermogenesis. β€’ Keywords: GLP1, Brown adipocyte, Diabetes, Exenatide, Incretin, Interleukin-6, Liraglutide β€’ Bioblast editor: Plangger M


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Diabetes 

Organism: Mouse  Tissue;cell: Fat 


Coupling state: LEAK  Pathway: S, ROX  HRR: Oxygraph-2k 

2022-11