Article date: June 1998
By: Bronwyn A Evans, Maria Papaioannou, Frank Anastasopoulos, Roger J Summers, in Volume 124, Issue 4, pages 763-771
Levels of β3‐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 β3‐AR agonist CL 316243 were also characterized in ileal longitudinal smooth muscle from obese and lean mice.
β3‐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, β3‐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.
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.
pKB values for the β1‐AR and β2‐AR selective antagonist propranolol or the β3‐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 β3‐AR.
Treatment of lean C57BL/6J mice with dexamethasone (1 mg kg−1, i.p.) significantly reduced β3‐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). β3‐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).
In summary, β3‐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 β3‐mRNA levels in ileum of obese and lean mice were associated with indistinguishable responses of carbachol‐contracted ileum to a β3‐agonist and similar affinity for β‐antagonists. Administration of glucocorticoids to lean mice reduced β3‐AR mRNA levels in WAT and BAT but not in ileum or colon. These studies show that in mice, β3‐ARs are differentially regulated in ileum and colon compared to adipose tissues.
Levels of β3‐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 β3‐AR agonist CL 316243 were also characterized in ileal longitudinal smooth muscle from obese and lean mice.
β3‐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, β3‐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.
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.
pKB values for the β1‐AR and β2‐AR selective antagonist propranolol or the β3‐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 β3‐AR.
Treatment of lean C57BL/6J mice with dexamethasone (1 mg kg−1, i.p.) significantly reduced β3‐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). β3‐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).
In summary, β3‐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 β3‐mRNA levels in ileum of obese and lean mice were associated with indistinguishable responses of carbachol‐contracted ileum to a β3‐agonist and similar affinity for β‐antagonists. Administration of glucocorticoids to lean mice reduced β3‐AR mRNA levels in WAT and BAT but not in ileum or colon. These studies show that in mice, β3‐ARs are differentially regulated in ileum and colon compared to adipose tissues.
DOI: 10.1038/sj.bjp.0701867
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