Subcutaneous adipose tissue dopamine D2 receptor is increased in prediabetes and T2D

Fig. 1. Dopamine receptors expression in human adipose tissue. A DRD1 and DRD2 mRNA expression in human SAT. n = 87, subjects without T2D, cohort 1. B DRD1 and DRD2 mRNA expression in human OAT. n = 52, cohort 2. C, E DRD1 and DRD2 mRNA expression in paired SAT and OAT. n = 52, cohort 2. D, F DRD1 and DRD2 protein expression in paired SAT and OAT. n = 7, cohort 2. G, H DRD1 and DRD2 total protein expression in mature adipocytes and SVF in SAT. n = 3, subjects without T2D, cohort 1. Western blot data are shown as relative to total protein and a representative immunoblot of total protein levels is provided in online resource 1. Data are shown as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. SAT subcutaneous adipose tissue, OAT omental adipose tissue, SVF stromal vascular fraction

Fig. 2. Dopamine receptors expression in SAT from subjects with and without T2D and obesity. A, C DRD1 and DRD2 mRNA expression in SAT of subjects with NGT, IFG, and T2D, n = 64/23/29, NGT/IFG/T2D from cohort 1. B, D DRD1 and DRD2 protein expression in SAT of subjects with NGT, IFG, and T2D from cohort 1, n = 4/4/7. E, G DRD1 and DRD2 gene expression in lean, overweight, and subjects with obesity. n = 25/44/18 from cohort 1. F, H DRD1 and DRD2 protein expression in SAT of lean subjects and subjects with obesity. n = 5/6 from cohort 1. Western blot data are shown as relative to total protein and a representative immunoblot of total protein is provided in online resource 1. Data are shown as mean ± SEM. *p < 0.05, **p < 0.01. SAT subcutaneous adipose tissue, NGT normal glucose tolerance, IFG impaired fasting glucose, T2D type 2 diabetes

Fig. 3. Impact of weight loss with bariatric surgery on DRD1 and DRD2 expression in SAT from subjects with obesity and T2D. A, B DRD1 and DRD2 mRNA expression in subjects with obesity and T2D at baseline and 4, 24, and 104 weeks post-RYGB, and in controls without obesity and T2D. n = 8–12 from cohort 1. C, D DRD1 and DRD2 protein expression in subjects with obesity and T2D at baseline and 4 weeks post-RYGB. n = 7–9 from cohort 1. Western blot data are shown as relative to total protein and a representative immunoblot of total protein levels is provided in online resource 1. Data are shown as mean ± SEM. *p < 0.05, **p < 0.01. SAT subcutaneous adipose tissue

Fig. 4. DRD1 and DRD2 protein expression correlation with markers of obesity and hyperglycemia. A–C DRD1 and D–F DRD2 protein expression association with BMI, HbA1c, and AUC glucose during an OGTT. Dopamine receptors expression in SAT from subjects with and without T2D and obesity. n = 4/4/7 for NGT/IFG/T2D from cohort 1. Significant Spearman correlation values are bolded, p < 0.05. NGT normal glucose tolerance, IFG impaired fasting glucose, T2D type 2 diabetes, BMI body mass index, HbA1c glycated hemoglobin

Fig. 5. Effects of dopamine and dopamine receptor agonists on subcutaneous adipocyte metabolism. Dopamine effects on (A) basal and insulin-stimulated adipocyte glucose uptake and on (B) basal and isoproterenol-stimulated adipocyte lipolysis. (n = 7 and 3 without T2D from cohort 1, respectively). SKF81297 (D1 receptor agonist) and bromocriptine (D2 receptor agonist) effects on (C) basal and insulin-stimulated adipocyte glucose uptake, and (D) basal and isoproterenol-stimulated adipocyte lipolysis (n = 3 and 4 without T2D from cohort 1, respectively). Data are shown as mean ± SEM. *p < 0.05, **p < 0.01. ISO isoproterenol