Triiodothyronine and amiodarone effects on β3‐adrenoceptor density and lipolytic response to the β3‐adrenergic agonist BRL 37344 in rat white adipocytes

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Abstract
Summary—The β‐adrenergic effects of catecholamines are potentiated by thyroid hormones in adipose tissue. Amiodarone (AM) is structurally similar to thyroid hormones and was used to explore the mechanism of the triiodothyronine (T3) effect on β‐adrenergic receptors (β‐ARs) in adipose tissue. AM decreases the expression of some T3sensitive genes in various tissues and antagonizes the effect of T3on its nuclear receptors. In this study, the T3, AM and AM + T3effects on the β1‐ and β3‐AR density were assessed on rat white adipocytes by radioligand binding using [3H]CGP 12177 after characterization of these subtypes by displacement of [3H]CGP 12177 binding by isoproterenol, BRL 37344 and noradrenaline. BRL 37344 was used to study β3‐AR lipolysis. White adipocytes from hyperthyroid rats had increased responsiveness (Emax× 2) and sensitivity (+ 38%) to BRL 37344, while those given AM alone had decreased values. Moreover, AM antagonized the T3effect on lipolysis. The β1‐binding characteristics (receptor density [Bmax]: 45 ± 4 fmol/mg of proteins; dissociation factor [Kd]: 0.96 ± 0.10 nM) were not modified by either compound. Finally, T3significantly increased β3‐AR density (587 ± 69 versus 363 ± 25 fmol/mg of proteins) and Kd(38 ± 2 versus 23 ± 3 nM), while AM alone had no effect and did not antagonize the T3effect on β3‐AR number. In conclusion, the hyperthyroid state in the rat potentiated the lipolytic response of white adipocytes to a specific β3‐agonist and increased the β3‐AR density without changing in β1‐AR number and affinity. Furthermore, the lack of antagonism between AM and T3on β3‐AR expression suggests that T3does not work directly on the β3‐AR gene. Moreover, AM induced a functional tissular hypothyroid‐like effect and its antilipolytic effect probably occurred at a postreceptor level.