The mediobasal hypothalamus regulates functions necessary for survival, including body energy balance and adaptation to stress. The purpose of this experiment was to determine the contribution of the arcuate nucleus (ARC) in controlling these two functions by the paraventricular nucleus (PVN). Circular, horizontal cuts (1.0 mm radius) were placed immediately above the anterior ARC to sever afferents to the PVN. In shams the knife was lowered to the same coordinates but was not rotated. Food intake and body weight were monitored twice daily, at the beginning and end of the light cycle, for 1 week. On the final day the animals were restrained for 30 min. Lesioned animals had increased food intake in light and dark periods, higher weight gain per day, and more body fat as compared with shams. There was no difference in caloric efficiency. Unlike shams, lesioned rats had no predictable relationship between plasma insulin and leptin.Plasma ACTH was increased at 0 min in lesioned rats but was decreased 15 and 30 min after restraint as compared with shams. There was no difference in plasma corticosterone. Immunostaining revealed that ␣-melanocortin (␣MSH) and neuropeptide Y (NPY) accumulated below the cuts, and both were decreased in PVN. Food intake and body weight were correlated negatively to ␣MSH, but not NPY in PVN. There was no difference in proopiomelanocortin (POMC) mRNA, but NPY mRNA was reduced in the ARC of lesioned animals. We conclude that ARC controls body energy balance in unstressed rats, possibly by ␣MSH input to PVN, and that ARC also is necessary for PVN regulation of ACTH.
Key words: ␣-melanocyte-stimulating hormone; neuropeptide Y; CRF; ACTH; restraint; hypothalamusCentral regulation of food intake, energy expenditure, and body weight gain is accomplished by activity in several brain sites; however, both genetic stimulation and lesion experiments suggest that the hypothalamus is critical to central integration of energy balance . The medial hypothalamic nuclei have different effects on energy balance; the effects of loss of normal activity in the ventromedial nuclei (VMN) and paraventricular nuclei (PVN) can be distinguished readily from each other (Tokunaga et al., 1986;Parkinson and Weingarten, 1990;. However, normal activity in both the PVN and arcuate nuclei (ARC) is required for maintenance of normal body weight, and the effects of lesions of these cell groups are difficult to distinguish from each other. Disruption of activity in either the ARC or PVN results in obesity characterized by increased food intake during both light and dark periods of the day and decreased weight loss during the light hours. Moreover, rats with lesions of ARC and PVN still respond to increased foodinduced obesity with increased thermogenesis that is mediated by sympathetic neural stimulation of uncoupling protein in brown adipose tissue (Ghorbani et al., 1997;.Endings from cell bodies in the ARC innervate the PVN quite strongly (Sawchenko and Swanson, 1983;Baker and Herkenham, 1995), and at least two peptides deriv...