Fig. 9: Chronic GIPR agonism desensitizes adipocyte GIPR activity in vivo mimicking GIPR antagonism.

GIP-stimulated FA uptake in DIO mice treated with vehicle, LA-Agonist, or muGIPR-Ab for 6 days. On day 6, mice were injected with saline or DA-GIP and simultaneously oral gavaged with ¹⁴C-oleic acid in olive oil to assess FA uptake. a Cumulative food intake determined; *p = 0.036, **p = 0.0075. b Fasting blood glucose and c plasma insulin were measured on day 6; ****p ≤ 0.0001. Data represent means ± SEM of 16 mice for vehicle group (divided into two groups of 8 for the FA uptake assay) and eight mice/group for the LA-Agonist and muGIPR-Ab groups. d Body weight, e scWAT weight, f eWAT weight, and g liver weight were measured at necropsy on day 6. Radioactivity uptake into metabolically relevant tissues was determined at necropsy in h scWAT, i eWAT, j liver, and k skeletal muscle. h Vehicle/DA-GIP vs. Vehicle/Saline *p = 0.027, Vehicle/DA-GIP vs. muGIPR-Ab/DA-GIP *p = 0.014, Vehicle/DA-GIP vs. LA-Agonist/DA-GIP *p = 0.014; j *p = 0.041. n = 8 mice/group. a–k One-way ANOVA with Sidak’s test for multiple comparisons; *p ≤ 0.05, **p ≤ 0.01, and ****p ≤ 0.0001. Data are presented as mean values ± SEM.