Fig. 8: Activation of adipocyte G_q signaling restores normal glucose and lipid homeostasis in adipocyte-specific insulin receptor (IR) mutant mice.

a Body weight gain of adipo-GqD-IR^+/- mice (adipocyte-specific heterozygous insulin receptor knockout mice expressing GqD in adipocytes) and control littermates (LSL-GqD-IR^+/flox mice that do not carry the adipoq-Cre transgene) maintained on a high fat diet (HFD). b–e Body composition (fat and. lean body mass) (b), plasma insulin levels after a 16 hr overnight fast (c), and fed and fasting (16 hr overnight) blood glucose (d) and plasma FFA levels (e) of adipo-GqD-IR^+/- mice and control littermates maintained on HFD for ~10 weeks. f–i, Blood glucose (f), plasma insulin (g), plasma FFA (h), and plasma glycerol (i) levels of HFD adipo-GqD-IR^+/- and control mice after acute treatment with CNO (10 mg/kg i.p.) following a 4 hr fast. j–l, GTT (j), ITT (k), and GSIS (l) performed with HFD adipo-Gq-IR^+/- mice and control littermates with or without CNO (10 mg/kg i.p.) treatment. In (j), mice were injected with 1 g/kg glucose (i.p.) after a 4 h fast. In (k) and (l), mice that had been fasted for 4 hr received 1 U/kg insulin (i.p) or a bolus of glucose (1 g/kg i.p.), respectively. m–o, NMLTC₄ treatment of HFD adipo-GqD-IR^+/- mice. m, n, Blood glucose (m) and plasma FFA (n) levels of HFD adipo-GqD-IR^+/- mice after treatment with NMLTC₄ (10 μg/kg) or saline following a 4 h fast. o, GTT. After a 4 h fast, HFD adipo-GqD-IR^+/- mice were injected with glucose (1 g/kg i.p.), either in the presence or absence of NMLTC₄ (10 μg/kg). All experiments were carried out with male mice maintained on HFD for 8–14 weeks Data are presented means ± s.e.m. (a, b: n = 10-14 per group; c–o: n = 5-8 per group). b–e, m, n: two-tailed Student’s t-test; f–l, o: two-way ANOVA followed by Bonferroni’s post hoc test) (f–l: adipo-GqD-IR^+/- plus CNO vs. adipo-GqD-IR^+/- without CNO). Source data are provided as a Source data file.