Chronic infusion of norepinephrine into the ventromedial hypothalamus induces obesity in rats.

To examine whether chronic increase in the local concentration of certain neurotransmitters in the hypothalamus might lead to some metabolic disorders in peripheral organs, several neurotransmitters and neuropeptides were infused continuously at a rate of 0.48 microliter/h for up to 20 weeks into the unilateral ventromedial (VMH), lateral or paraventricular hypothalamic nucleus of rats. A massive obesity with marked increase in body weight was observed after about 10 weeks when norepinephrine (NE) was infused chronically into the VMH, but not into other hypothalamic loci. Plasma insulin level went up markedly at the early stage of NE infusion and remained high during the infusion period, but plasma glucose did not change appreciably. Similar, but less pronounced effects were observed with epinephrine infusion into the VMH. However, other neurotransmitters and neuropeptides tested had no such effects. The NE-induced obese rats showed hyperphagia and an arrhythmic feeding pattern with increased daytime feeding. Chemical composition and the rate of fatty acid synthesis in the interscapular brown adipose tissue (BAT) were also altered after NE infusion into the VMH: although the triglyceride content was increased, the rate of fatty acid synthesis was decreased, indicating that triglyceride turnover in BAT was greatly reduced. The latter observation suggests that energy dissipation in BAT is impaired and this functional abnormality in BAT may also contribute to the development or maintenance of a new type of hypothalamic obesity induced by NE infusion.