Differential regulation of beta3-adrenoceptors in gut and adipose tissue of genetically obese (ob/ob) C57BL/6J-mice.

1. Levels of beta3-adrenoceptor (AR) mRNA were compared using reverse transcription-polymerase chain reaction (RT PCR) in white adipose tissue (WAT), brown adipose tissue (BAT), ileum and colon from genetically obese (ob/ob) and lean (+/+) C57BL/6J mice. Functional responses to the beta3-AR agonist CL 316243 were also characterized in ileal longitudinal smooth muscle from obese and lean mice. 2. Beta3-AR mRNA levels were significantly higher in WAT (100+/-16%) and BAT (100+/-13%) from lean compared to WAT (21.0+/-0.9%; n=4; P<0.005) and BAT (14.1+/-2.2%; n=5; P<0.01) from obese mice. In contrast, beta3-mRNA levels were not significantly different in ileum (100+/-15%) and colon (100+/-22%) from lean mice, compared to ileum (78+/-13%; n=4; P= 0.31) or colon (82+/-15%; n =4; P=0.52) from obese mice. 3. Concentration-response curves to CL 316243 did not differ significantly in slope or position in ileal longitudinal smooth muscle from obese or lean mice. pEC50 (+/-s.e.mean) values were not significantly different (P= 0.59) between obese (7.90+/-0.13, n = 7) and lean (7.77+/-0.20, n = 7) mice. 4. pKB values for the beta1-AR and beta2-AR selective antagonist propranolol or the beta3-AR selective antagonist SR 58894 against relaxations to CL 316243 were similar in ileum of genetically obese (propranolol 6.31+/-0.22 and 6.13+/-0.12; SR 58894 8.22+/-0.06) and lean mice (propranolol 6.40+/-0.08 and 6.60+/-0.13; SR 58894 8.27+/-0.12) and were consistent with values previously found at beta3-AR. 5. Treatment of lean C57BL/6J mice with dexamethasone (1 mg kg(-1), i.p.) significantly reduced beta3-AR mRNA levels after 4 h in WAT (100+/-6.1 to 41.4+/-4.3; n= 16 18; P<0.0001) and BAT (100+/-8.0 to 35.1+/-5.8; n= 17; P<0.0001), but caused no change in ileum (100+/-6.1 to 101+/-17; n= 10-11; P=0.95) or colon (100+/-11 to 101+/-11; n= 11; P= 0.94). Beta3-mRNA levels in ileum and colon also did not change significantly when examined over 24 h or after the administration of a higher dose of dexamethasone (5 mg kg(-1)). 6. In summary, beta3-AR mRNA levels were considerably lower in WAT and BAT of obese compared to lean mice whereas the levels in ileum and colon were not significantly different. The similar beta3-mRNA levels in ileum of obese and lean mice were associated with indistinguishable responses of carbachol-contracted ileum to a beta3-agonist and similar affinity for beta-antagonists. Administration of glucocorticoids to lean mice reduced beta3-AR mRNA levels in WAT and BAT but not in ileum or colon. These studies show that in mice, beta3-ARs are differentially regulated in ileum and colon compared to adipose tissues.