Leukemia inhibitory factor stimulates muscle glucose uptake by a PI3-kinase dependent pathway that is maintained in white muscle in obesity

Nina Brandt, Hayley M. O'Neill, Maximilian Kleinert, Peter Schjerling, Gregory R Steinberg, Erik A Richter, Sebastian Beck Jorgensen

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Abstract

OBJECTIVE: To investigates the metabolic effects of leukemia inhibitory factor (LIF) in mouse skeletal muscle. METHODS: Effects of LIF on muscle glucose transport, palmitate oxidation and cellular signaling were investigated in soleus and extensor digitorum longus (EDL) muscles from chow and highfat diet fed wildtype (WT) mice or chow fed muscle-specific AMPKα2 kinase-dead (KD) and suppressors of cytokine signaling (SOCS) 3 muscle-specific knockout mice. RESULTS: LIF increased muscle glucose transport in a dose- and time-dependent manner. LIF increased Akt Ser473-P, whereas AMPK Thr172-P was unaffected. Incubation of muscles from KD or WT mice with Wortmannin, LY294002 and Parthenolide demonstrated that PI3-kinase, but not AMPK, was essential for LIF-stimulated glucose transport. Incubation with Rapamycin and AZD8055 demonstrated that mammalian target of rapamycin complex (mTORC)2 and not mTORC1 is necessary for LIF-stimulated glucose transport. LIF-stimulated glucose transport was maintained in EDL muscle from obese insulin resistant mice. Lack of SOCS3 did not affect LIF-stimulated glucose uptake. CONCLUSIONS: LIF acutely increases muscle glucose transport by a mechanism involving the PI3-kinase/mTORC2/Akt pathway which is maintained in EDL muscle from obese insulin resistant mice.
Original languageEnglish
Article number1162.4
JournalThe FASEB Journal
Volume28
Issue number1_Suppl
Publication statusPublished - 1 Apr 2014
Externally publishedYes
EventThe ASPET Annual Meeting at Experimental Biology - San Diego, United States
Duration: 26 Apr 201430 Apr 2014
https://www.aspet.org/aspet/meetings-awards/meetingsannual-meeting/annual-meeting-archives/experimental-biology-2014

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    Brandt, N., O'Neill, H. M., Kleinert, M., Schjerling, P., Steinberg, G. R., Richter, E. A., & Jorgensen, S. B. (2014). Leukemia inhibitory factor stimulates muscle glucose uptake by a PI3-kinase dependent pathway that is maintained in white muscle in obesity. The FASEB Journal, 28(1_Suppl), [1162.4].