Activation of brown adipose tissue thermogenesis by chemical stimulation of the posterior hypothalamus

Abstract

The posterior hypothalamus (PH) is involved in the generation of behavioral thermoregulatory responses, but the importance of the PH in the control of autonomic thermoregulatory responses such as heat production in brown adipose tissue (BAT) is not well defined. In the present study, selective stimulation of PH neurons by local application of the excitatory amino acid glutamate (250 nl of 1 M solution, unilaterally) caused a sharp, transient increase in interscapular BAT (IBAT) and core temperature in urethane-anesthetized rats. This effect was blocked by pretreatment with the sympathetic ganglionic blocker, chlorisondamine chloride (2 mg/kg) or the beta-adrenergic receptor blocker, propranolol (2 mg/kg), implicating the involvement of the sympathetic system. The effect of intra-PH injection of glutamate on IBAT and core temperatures could be mimicked by injection of the gamma-aminobutyric acid (GABA) receptor antagonist, bicucullin methiodide (BMI, 50 ng), into the same PH site. This effect of BMI could be blocked by co-injection of the GABA(A) receptor agonist, muscimol (25 ng). Further, BMI co-injection potentiated the effect of intra-PH injection of glutamate on IBAT and core temperatures. Conversely, muscimol co-injection prevented the stimulatory effect of intra-PH injection of glutamate. Taken together, the results indicate that direct chemical stimulation of neurons in the PH can activate an autonomic mechanism controlling heat production in BAT. Further, they suggest the neural mechanism in the PH mediating this effect is tonically inhibited by GABA, as blockade of GABAergic function in the PH produces an effect similar to that observed after direct stimulation of PH neurons with glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)