Sexual dimorphism in the adrenergic control of rat brown adipose tissue response to overfeeding

Abstract.

Gender-related differences in the brown adipose tissue (BAT) response to overfeeding rats on a cafeteria diet were studied by assessing the balance between the expression of β-adrenoceptors (β₁-, β₂-, β₃-AR) and α_2A-AR and their relation to the expression of uncoupling proteins (UCP1, UCP2, UCP3). Cafeteria diet feeding for 15 days, which involved a similar degree of hyperphagia in both sexes, led to a greater body weight excess in females than in males and a lower activation of thermogenesis. Gender-related differences were found for different adrenoceptor expression and protein levels, which might explain, in part, sex differences in the thermogenic parameters. The lower expression of α_2A-AR in females than in males could be responsible for the higher expression of UCP1 and thermogenic capacity under non-hyperphagic conditions. However, in a situation of high adrenergic stimulation – as occurs with overfeeding – as there is a preferential recruitment of the β₃-AR by noradrenaline compared with other adrenergic receptors, the higher levels of β₃-AR in males rats than in females could be responsible for the greater thermogenic capacity and the lesser weight gain in males. Thus, the α₂/β₃ balance in BAT could be a key in the thermogenic control.