Differential Input from the Amygdaloid Body to the Ventromedial Hypothalamic Nucleus in the Rat

Differential amygdaloid afferents to anterior dorsal, anterior ventral, posterior dorsal and posterior ventral subdivisions of the ventromedial hypothalamic nucleus (VMH) were studied by means of retrograde transport of horseradish peroxidase (HRP). Injections of tracer confined to the VMH subdivisions mentioned, and enhancement of tracer uptake and transport were achieved by iontophoretic delivery of an HRP solution containing poly-L-α-ornithine. It was shown that the medial, central, basolateral, basomedial, lateroposterior and intercalated nuclei of the amygdala constitute afferent input sources to the ventromedial nucleus in a topographic pattern related to the various subdivisions of the VMH. This topographically organized amygdala-VMH projection is discussed against the background of the functional role that both amygdala and VMH play in the control of feeding, apart from various other autonomous functions that both brain centers are known to be concerned with.

Circulating free fatty acids, insulin, and glucose during chemical stimulation of hypothalamus in rats

The aim of this study was to investigate plasma free fatty acids (FFA), insulin, and blood glucose during chemical stimulation of the lateral and ventromedial hypothalamic areas (LHA and VMH) in rats. Therefore male Wistar rats were implanted with bilateral cannulas in the LHA or the VMH and into the left and right jugular veins. Freely moving rats were then infused into the LHA and VMH with norepinephrine (NE), epinephrine (E), or acetylcholine or intravenously with NE or E. Before, during, and after the infusions, simultaneous blood samples were taken without disturbing the animals. Infusion of NE into the LHA resulted in a decrease of plasma FFA and a simultaneous increase of insulin. NE infusion in the VMH elicited an increase of plasma FFA, plasma insulin, and blood glucose. E infusion into the LHA did not lead to a change of plasma FFA, whereas insulin and glucose showed an increase. E infusion into the VMH evoked increases of plasma FFA and insulin. Peripheral administration of NE led to a sharp increase of FFA, whereas plasma insulin and blood glucose did not change. E in the periphery elicited an augmentation of plasma FFA and blood glucose and a suppression of insulin during infusion. After termination of E infusion, plasma FFA and glucose levels decreased, whereas plasma insulin showed a sharp increase. It is concluded 1) that the effects produced by administration of NE and E are dependent on hypothalamic localization and local receptor population characteristics; 2) that there are striking differences regarding the effects on the investigated blood parameters between hypothalamically infused NE and E and peripherally infused NE and E; and 3) that the LHA and VMH are able to alter plasma FFA levels independently of blood glucose and insulin levels.

Human Pancreas GH-Releasing Factor Analog Restores High-Amplitude GH Pulses in CNS Lesion-Induced GH Deficiency

Lesions of the ventromedial-arcuate (VMH-ARC) region of the hypothalamus result in impaired growth accompanied by a marked suppression in spontaneous GH secretory bursts. We studied the effects of an analog of the recently characterized human pancreas GH-releasing factor hpGRF (1-40) on GH secretory dynamics in freely moving chronically cannulated rats bearing electrolytic lesions of the VMH-ARC. Intravenous administration of the hpGRF analog (hpGRFa) caused a dramatic surge of GH within 5 min; plasma GH levels rose to values as high as 2900 ng/ml and remained significantly elevated for 15-30 min post treatment. The simultaneous iv administration of somatostatin-14 and hpGRFa resulted in a significant inhibition of the hpGRFa-induced GH release at 5 min but not at 15 min. These results clearly demonstrate that impaired GH secretion resulting from VMH-ARC lesions can be restored by hpGRF. The findings are promising in that hpGRF and its analogs may provide valuable agents for the diagnosis and treatment of disorders of growth secondary to CNS dysfunction

Effects of Obesity-Inducing Ventromedial Hypothalamic Lesions on Pulsatile Growth Hormone and Insulin Secretion: Evidence for the Existence of a Growth Hormone-Releasing Factor

The nature of and neural mechanisms involved in GH and insulin responses to obesity-inducing ventromedial hypothalamic (VMH) lesions, which infringed on the arcuate nucleus, were examined in freely moving chronically cannulated male rats. Sequential 6-h GH and 3-h insulin and glucose secretory profiles were obtained in VMH-lesioned and sham-operated control rats. Obese VMH rats exhibited hyperinsulinemia with marked fluctuations in plasma insulin levels in the presence of normoglycemia. A striking suppression in both amplitude and duration of GH secretory episodes was observed, with GH peak amplitudes rarely exceeding 90 ng/ml compared to 500 ng/ml in sham-operated controls (mean 6-h plasma GH level, 17.6 ± 6.0 vs. 154.1 ± 17.8 ng/ml; P \u3c 0.001). The periodicity of the GH rhythm was maintained, but light-dark entrainment of the GH pulses was lost. Passive immunization with a specific antiserum to somatostatin (SRIF) failed to restore the amplitude of the GH peaks or to alter significantly the 6-h GH secretory profile of VMH-lesioned animals. In contrast, the administration of SRIF antiserum to sham-operated controls caused a significant elevation of GH trough levels. In a second study, obese VMHl-esioned rats exhibited reduced pituitary GH concentrations compared to sham-operated controls. The finding of a lack of effect of SRIF antiserum in VMHl-esioned rats provides good evidence that the suppression of GH pulses observed in response to lesions of the VMH is due to interruption of stimulatory pathways involved in GH regulation, namely GH-releasing factor neurons. The results suggest that the ultradian surges of GH release are dependent on the release of GH-releasing factor from the VMH-arcuate nucleus region of the brain. The data are consistent with the view that the obesity and GH suppression of the VMH syndrome reflect the disruption of two different neuronal systems

Disruption of type 3 adenylyl cyclase expression in the hypothalamus leads to obesity

Evidence from human studies and transgenic mice lacking the type 3 adenylyl cyclase (AC3) indicates that AC3 plays a role in the regulation of body weight. It is unknown in which brain region AC3 exerts such an effect. We examined the role of AC3 in the hypothalamus for body weight control using a floxed AC3 mouse strain. Here, we report that AC3 flox/flox mice became obese after the administration of AAV-CRE-GFP into the hypothalamus. Both male and female AC3 floxed mice showed heavier body weight than AAV-GFP injected control mice. Furthermore, mice with selective ablation of AC3 expression in the ventromedial hypothalamus also showed increased body weight and food consumption. Our results indicated that AC3 in the hypothalamus regulates energy balance

Phaseolus vulgaris leuco-agglutinin immunohistochemistry. A comparison between autoradiographic and lectin tracing of neuronal efferents

The autoradiographic pattern of anterograde labeling as a result from injections with tritiated amino acids is compared to the labeling of efferents with Phaseolus vulgaris leuco-agglutinin after lectin injections in the same nucleus visualized by immunohistochemical methods. This comparison is made for efferents from the ventromedial hypothalamic nucleus to the amygdaloid body.

A Third Variable in Obesity: The Effects of Brown Adipose Tissue on Thermogenesis

Approaches to weight management which consider only energy intake and/or expenditure do not consistently lead to favorable outcomes. A third variable, thermogenesis, must also be considered in a comprehensive understanding of obesity· Three types of thermogenesis have been outlined-shivering thermogenesis, nonshivering thermogenesis (NST), and diet-induced thermogenesis (DIT). The latter two types of thermogenesis, NST and DIT, may share a common biochemical mechanism which leads to heat production in brown adipose tissue (BAT) which is unchecked by energy needs. Four categories of studies are reviewed which implicate BAT as an important factor in DIT and point to commonalities in NST and DIT. More research is necessary to fully understand the role of BAT in human obesity