Differential regulation of β₃-adrenoceptors in gut and adipose tissue of genetically obese (ob/ob) C57BL/6J-mice

Abstract

1. 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.

2. 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.

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. pK_B 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.

5. 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).

6. 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.

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