Intra-ventromedial hypothalamic injection of insulin suppresses brown fat thermogenesis in the anaesthetized rat

Insulin can affect metabolic functions such as glucose production and fat mobilization through action in the ventromedial nucleus of the hypothalamus (VMH), and the VMH has been implicated in the regulation of heat generation in brown adipose tissue (BAT) in the rat. To study the role of insulin in modulating VMH mechanisms concerned with BAT thermogenic activity we evaluated the effect of intra-VMH microinjection of insulin on BAT (T_bat) and core (T_core) temperatures and BAT thermogenic activity (T_bat−T_core) in anaesthetized rats. Intra-VMH insulin (10 ng, 100 ng and 1 μg) enhanced the decreases in T_bat and T_core resulting from exposure of the anaesthetized rats to mild cold, as well as diminished BAT thermogenic activity in a dose-dependent manner. This effect could be partially reversed by systemic treatment with norepinephrine (400 μg/kg). Intra-VMH injection of insulin analogs having reduced binding affinity to insulin receptors and diminished biological activity - i.e. acetyl₃ insulin, succinyl₃ insulin and TNB₃ insulin was much less effective at enhancing the decrease in T_bat and T_core or at inhibiting BAT thermogenic activity. These results demonstrate that insulin can modulate BAT thermogenesis in a specific manner through action in the VMH.