Selective activation of brown adipocyte hormone-sensitive lipase and cAMP production in the mouse by β3-adrenoceptor agonists

• Published in: Biochemical pharmacology 1995-08, Vol.50 (5), p.601-608
• Main Authors: Shih, Mei-Fen, Taberner, Peter V.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; cAMP; Fundamental and applied biological sciences. Psychology; hormone-sensitive lipase; Vertebrates: skin, associated glands, phaneres, light organs, various exocrine glands (salt gland, uropygial gland...), adipose tissue, connective tissue; β3-adrenoceptor
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(95)00185-3

Acute injection of either noradrenaline or isoprenaline in mice activated both brown (BAT) and white (WAT) adipose tissue hormone-sensitive lipase activity (HSL). Dose-response studies indicated that isoprenaline (0.05–0.15 mg/kg) produced a dose-dependent activation of HSL in both BAT and WAT, whereas SR 58611A produced no change in HSL in WAT over a dose range (1–5 mg/ kg) which, at the same time, dose-dependently increased HSL activity in BAT. The other β 3-adrenoceptor agonists, ZD 7114 (10 mg/kg) and BRL 35135 A (5 mg/kg) also selectively increased HSL activity in BAT, these doses having previously been shown to stimulate lipogenesis in vivo. Higher doses of ZD 7114 and BRL 35135 produced no further increase in HSL activity and, in the case of BRL 35135, provoked symptoms of non-selective β-adrenoceptor activation. The increase in HSL activity could be prevented by pretreating the mice with propranolol, 10 mg/kg, i.p., 30 min prior to the agonist. The activation of HSL activity by the β 3-adrenoceptor agonists was associated with an increase in tissue cAMP production which was also prevented by pretreatment with propranolol. The degree of cAMP accumulation was least with BRL 35135 and greatest with ZD 7114. We conclude that, in the mouse adipocyte, the atypical β-adrenoceptor ( β 3) is present in BAT, but is not present or functional in WAT.