Figure 7.

GPR3 is an essential activator of human thermogenic adipocytes

(A) Structural location (snake plot) and disease association (table) of human GPR3 variant, A27G.

(B) Functional consequence of A27G mutation on GPR3 cAMP-inducing activity.

(C) Correlation between BAT GPR3 expression and body mass index (BMI) in glucose tolerant and glucose intolerant individuals.

(D) Schematic of GPR3 loss-of-function and gain-of-function studies in patient-derived, non-immortalized brown adipocytes.

(E) Gene expression of siRNA-mediated GPR3 knockdown and 4-h vehicle or norepinephrine (NE) treatment of patient-derived, non-immortalized brown adipocytes.

(F and G) Pathway analysis of gene networks (F) reduced by GPR3 depletion and (G) induced by GPR3 activation in patient-derived, non-immortalized brown adipocytes.

(H) Gene expression following siRNA-mediated GPR3 knockdown and 4-h vehicle or NE treatment of patient-derived, non-immortalized brown adipocytes.

(I) Change in the gene expression of Gs-coupled GPCRs in human brown adipocytes following siRNA-mediated GPR3 knockdown.

(J) Correlation between GPR3 and ADRB1 expression in human BAT.

(K and L) Correlation between (K) GPR3 and ADRB2 and (L) GPR3 and UCP1 expression in human scWAT.

(M) GPR3 expression in scWAT before and after bariatric surgery (NonOB, non-obese; OB, obese; PostOB, post-obese).

(N–P) (N) Gene expression, (O) leak respiration, and (P) fatty acid (FA) uptake in human subcutaneous white adipocytes in which GPR3 expression has been induced by CRISPR/Cas9-engineering.

(Q) Pathway analysis of gene networks induced by GPR3 in CRISPR/Cas9-engineered human subcutaneous white adipocytes.

For all panels, error bars represent ±SEM, p ≤ 0.05 = ∗, p ≤ 0.01 = ∗∗, p ≤ 0.001 = ∗∗∗, p ≤ 0.0001 = ∗∗∗∗, t test (E, H, I, and M–P), two-way ANOVA (B), simple linear regression (C and J–L), or Fisher’s exact test (F, G, and Q). Box plots are presented as box: 25^th to 75^th percentile, and whiskers: min to max. See also Figures S6 and S7.