Figure 5.

AdipoRon treatment for 20 days exacerbated whole-body insulin resistance.A, diagram of the AdipoRon treatment regimen in vivo. Briefly, mice fed the HFD for 18 days were subcutaneously injected with AdipoRon at 5 mg kg⁻¹ BW daily with or without the anti-FGF21 antibody (10.7 μg/mouse). DMSO-treated mice were used as vehicle controls. B, concentrations of circulating FGF21 in feeding mice. C, BW. D, time course of food intake after intervention. E, concentrations of circulating leptin in feeding mice. F and G, representative images of Oil Red O staining of the liver and hepatic lipid contents. H and I, serum concentrations of ALT, AST, TC, TG, HDL, and LDL. J, lipid contents in the skeletal muscle (gastrocnemius and soleus). K, fasting serum glucose concentrations. L, hepatic acetyl-CoA contents. M, time course of blood glucose concentrations during the GTT. N, AUC of the GTT. O, time course of blood glucose and the GIR during clamping. P, the GIR in the steady clamping state. Q, EGP during basal infusion and clamping. R, EGP suppression. S, whole-body glucose disposal rates. T, circulating FFA concentrations in the fasting and clamping states. U, representative IF images of PLIN1 and MGL in WAT. V, metabolic flux analysis in skeletal muscle (gastrocnemius and soleus). Data are presented as the mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001. ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve; BW, body weight; DMSO, dimethyl sulfoxide; EGP, endogenous glucose production; FFA, free fatty acid; FGF21, fibroblast growth factor 21; GIR, glucose infusion rate; GTT, glucose tolerance test; HDL, high-density lipoprotein; HFD, high-fat diet; IF, immunofluorescence; LDL, low-density lipoprotein; MGL, monoacylglycerol lipase; PLIN1, perilipin 1; TC, total cholesterol; TG, triglyceride; WAT, white adipose tissue.