Fig. 5: Knockdown of MAFG-dependent LincIRS2 causes mild insulin resistance in lean mice.
From: A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism
a qPCR of LincIRS2 expression in the liver from C57BL/6N mice treated with Scr LNA (n = 7), Mafg LNA (n = 8), Control ASO (n = 10), or Mafg ASO (n = 7). b–f qPCR for LincIRS2 expression in primary hepatocytes after b 24 h of transduction with adenoviruses (Ad)-expressing caChREBP and caFOXO1, c 16 h of 200 nM GCG and 100 µM cAMP, d 6 h of 27.5 mM glucose, and/or e 100 nM insulin in livers from mice with hepatocyte-specific IR knockout vs. Cre-negative Controls59 (n = 3). f Twenty-four hours after transduction of primary hepatocytes with Ad-caSREBP1c. g qPCR of LincIRS2 expression after transfection of primary hepatocytes with 100 nM LincIRS2 or Scr LNAs and 6 h of stimulation with g FD and GCG or h insulin. g, h n = 6–10 independent experiments, each in triplicate. i–k qPCR of Pck1 expression after transfection with 100 nM LincIRS2 or Scr LNAs and 6 h of stimulation with i insulin, j FD, or k GCG. i–k n = 5–10 experiments, each in triplicates. l qPCR of LincIRS2 expression in indicated tissues from 21-week-old CD-fed mice after 15 weeks of 10 mg kg−1 LincIRS2 or Scr LNA (n = 4) treatment. m, n Body weight in m CD- and n HFD-fed C57BL/6N mice during 15 weeks of LincIRS2 LNA or Scr LNA (n = 8) treatment. o Fasted and random-fed GTT and ITT in CD-fed 12- and 11-week-old C57BL/6N mice after 6 and 5 weeks of LincIRS2 or Scr LNA (n = 8) treatment. p Fasted and random-fed glucose and ITT in HFD-fed 12- and 11-week-old C57BL/6N mice after 6 and 5 weeks of LincIRS2 or Scr LNA (n = 8 each) treatment. q, r Representative immunoblot and densitometry of t-AKT and pAKTS473 in p CD- or r HFD-fed C57BL/6N mice after 15 weeks of LincIRS2 or Scr LNA treatment injected with 2.5 µl g−1 BW NaCl 0.9% or 0.1 U/mouse insulin (n = 3). Bar graphs represent mean ± s.e.m. with all data plotted and statistical differences calculated using (a–i), l unpaired, two-tailed Student’s t test. q One-way ANOVA or m–p two-way ANOVA with Bonferroni post correction for multiple testing. *p < 0.05, **p < 0.01, ***p < 0.001. Source data are provided as a Source Data file.
