Figure 3. ADRB3 mediates brown adipocyte-derived IL6 in response to acute stress.

(A) Circulating IL6 levels (n=7 per group) and (B) mRNA expression of Il6 post bleeding in Ucp1 KO or WT mice (n=7 for WT, n=11 for WT + bleed, n=7 for Ucp1 KO, n=10 for Ucp1 KO + bleed). NT, no treatment. BAT, brown adipose tissue. eWAT, epididymal white adipose tissue.

(C) Plasma IL6 levels in mice bled or restrained after anesthesia induced by ketamine/xylazine or isoflurane (n=5 per group, representative of 2 experiments). NT, no treatment. TR, tube restraint.

(D) Circulating IL6 post bleeding from mice with chemical denervation of brown adipose tissue via 6-hydroxydopamine (6-OHDA) administration (n=3 per group).

(E) Circulating IL6 levels and (F) mRNA expression of Il6 two hours post injection of beta-adrenergic receptor agonists (n=5 per group). ADRB1/2: isoproterenol, ADRB1 and ADRB2 agonist. ADRB3: CL316,243, ADRB3 agonist. FB, forebrain. Adrenal, Adrenal gland. BAT, brown adipose tissue.

(G) Plasma level of IL6 post bleeding at indicated time points from mice pre-treated with the ADRB3 antagonist SR59203A (n=5 per group).

(H) Plasma level of IL6 post bleeding in Adrb1/2 KO or Adrb3 KO mice (n=5 per group). NT, no treatment.

(I) Plasma level of IL6 post bleeding from mice with conditional UCP1-mediated Adrb3 deletion (Adrb3f/f^ΔUCP1) or littermate controls (Adrb3f/f) (n=5 per group). NT, no treatment. * p<0.05, **p<0.01, *** p<0.001, **** p<0.0001

See also Figure S1 and S7.