Takashi Shimazu

Accelerated norepinephrine turnover in peripheral tissues after ventromedial hypothalamic stimulation in rats

To obtain evidence for a functional connection between the ventromedial hypothalamic nucleus (VMH) and the sympathetic nervous system, effects of electrical stimulation of the VMH, the lateral hypothalamic area (LH) and the paraventricular hypothalamic nucleus (PVN) on norepinephrine (NE) turnover in the heart, liver, pancreas, spleen, submandibular gland and the interscapular brown adipose tissue were examined in anesthetized rats. Stimulation of the VMH elicited a 3-8-fold increase in the rate of NE turnover in all organs examined, whereas stimulation of the LH or the PVN had no appreciable effects. The effect of VMH stimulation was abolished after sympathetic ganglionic blockade with hexamethonium. Epinephrine turnover in the adrenal gland was accelerated by stimulation of not only the VMH but also the LH. It was concluded that the VMH is intimately associated with sympathetic facilitation in peripheral tissues.

Role of the hypothalamus in insulin-independent glucose uptake in peripheral tissues

To clarify the role of the ventromedial hypothalamus (VMH)-sympathetic nervous system in insulin-independent glucose uptake in peripheral tissues, tissue glucose uptake was assessed in vivo by the 2-[3H]deoxyglucose method during electrical stimulation of the VMH in anesthetized rats. VMH stimulation significantly increased the rate constant of glucose uptake in brown adipose tissue (BAT), heart and skeletal muscles, but not in white adipose tissue and brain. The effect of VMH stimulation on glucose uptake in BAT was abolished by local sympathetic denervation, indicating that the increase in glucose uptake is mediated by the sympathetic nerves. Electrical stimulation of the lateral hypothalamus, on the other hand, had no appreciable effects on 2-[3H]deoxyglucose uptake in any tissues. Changes in glucose transporters after VMH stimulation were also examined by the [3H]cytochalasin B binding method using sarcolemmal membranes isolated from heart muscle. Scatchard analysis of cytochalasin B binding indicated that VMH stimulation did not alter both the number and affinity (dissociation constant) of glucose transporters in the heart sarcolemmal membranes, whereas insulin administration increased the number of transporters in the membranes. These results suggest that the mechanism by which VMH stimulation increases glucose uptake in muscle is different from that of insulin.

Neuropeptide Y in the specific hypothalamic nuclei of rats treated neonatally with monosodium glutamate.

Neuropeptide Y (NPY) concentration was determined by radioimmunoassay in selected hypothalamic regions microdissected from fresh brain slices of rats treated neonatally with monosodium glutamate (MSG). Fourteen weeks after MSG treatment, significant decreases in NPY concentration were found in the paraventricular nucleus (PVN) and arcuate nucleus (ARH), while there was no appreciable change in the ventromedial nucleus (VMH) and lateral area (LH). The decrease in NPY in the ARH-PVN system may contribute to the endocrine and metabolic disturbances seen in MSG-treated animals.

Sympathetic activation of lipid synthesis in brown adipose tissue in the rat.

1. The roles of the sympathetic nerves in regulating lipid synthesis in brown adipose tissue (BAT) were studied by measuring incorporation of 3H from 3H2O into glyceride glycerol and glyceride fatty acids in the interscapular BAT in anaesthetized rats. 2. When noradrenaline was infused intravenously at a total dose of 1‐8 micrograms/100 g body weight over 30 min, 3H incorporation into glyceride glycerol increased whereas 3H incorporation into fatty acids did not change. Similar responses were found when the sympathetic nerves entering the interscapular BAT were stimulated continuously at 10 Hz. However, when electrical stimuli consisting of a much shorter train (2 s) were applied to the nerves at 3 min intervals at 10 Hz (stimulation in bursts). 3H incorporation into both glyceride glycerol and fatty acids was enhanced. Stimulation in bursts elicited more pronounced lipogenic responses than other patterns that were employed, and involved the delivery of precisely the same number of impulses over the whole period of stimulation. The lipogenic responses to nerve stimulation in bursts were increased by increasing the stimulus frequency over the range 4‐40 Hz. 3. Simultaneous administration of propranolol and phenoxybenzamine had little effect on either the fatty acid or the glyceride glycerol response to nerve stimulation. In contrast, these blocking agents almost completely eliminated the responses to noradrenaline infusion. 4. Pre‐treatment with guanethidine effectively abolished the lipogenic response to nerve stimulation but potentiated the response to noradrenaline infusion. 5. It is concluded that lipid synthesis in BAT is enhanced by direct electrical stimulation of the sympathetic nerves only when they are stimulated in bursts. Sympathetic activation of lipogenesis in BAT is not solely attributable to the action of noradrenaline but involves some non‐adrenergic mechanism.

Adrenergic blockade paradoxically increases lipogenic response of brown adipose tissue to sympathetic nerve stimulation

Intermittent electrical stimulation of sympathetic nerves entering the interscapular brown adipose tissue (BAT) in rats increased the rate of glyceride glycerol synthesis in BAT but the fatty acid synthesis did not change. Simultaneous administration of phenoxybenzamine and propranolol paradoxically increased the fatty acid synthesis in response to the nerve stimulation whereas the glyceride glycerol synthesis was inhibited. Propranolol alone was also effective in mimicking the effects of adrenergic blockade, but guanethidine selectively eliminated the lipogenic response to the nerve stimulation. These results indicate that synthesis of glyceride glycerol induced by sympathetic nerve stimulation is largely due to beta-adrenergic action of noradrenaline, whereas synthesis of fatty acids may be mediated by non-adrenergic transmission of the sympathetic nerves.