The Effect of Ventromedial Hypothalamic Lesions on Metabolism and Insulin Secretion in Rats on a Controlled Feeding Regimen

Abstract

The metabolic effect of ventromedial hypothalamic (VMH) lesions, which are known to cause hyperphagia and obesity, has been studied in rats kept on a controlled light and food regimen. The animals were sacrificed at 4 different times during the second postoperative day. A feeding-induced hypersecretion of insulin was found in the VMH-lesioned animals. It was accompanied by a marked hypoglycemia as compared to the control groups during the feeding period. The glycogen content of liver and diaphragm in the lesioned groups is increased as compared to the controls during the same period. The VMH-lesioned animals showed hypertriglyceridemia both in the fed and fasted state, whereas the postabsorptive plasma levels of free fatty acids and glycerol were decreased. An increased level of urea was observed in all lesioned groups. This is in accordance with the demonstrated protein catabolism which follows VMH lesions.

Continuous carbachol infusion promotes peripheral cell proliferation and mimics vagus hyperactivity in a rat model of hypothalamic obesity

“…2). In fact, VMHlesioned rats often showed extremely enlarged pancreatic islets (not shown), which may result in hyperinsulinemia in the VMH-lesioned rats (2,18,22,24,38). During pancreatic regeneration or aging, newly produced B-cells are derived from the pre-existing B-cells within the islets (12).…”

“…The ventromedial hypothalamus (VMH) mediates important neural pathways for feeding behavior in various animals, including cats, mice, rats, and humans (1,3,13,22,40). Lesions of the VMH result in a metabolic obesity syndrome of endogenous hyperinsulinemia, insulin resistance, low sympathetic activity, and high parasympathetic tone (18,25,53) that is mediated by various factors, including neuropeptide Y (14,43), orexins (19), ghrelin (9,51), melanin-concentrating hormone (5,11,15,36,39), neuromedin U (21), leptin (4,17,42,48), melanocortin (20), corticotropin-releasing hormone (44,46,47), and brain-derived neurotrophic factor (27,45,52).…”

Consequences of Ventromedial Hypothalamic Lesions upon Insulin and Glucagon Secretion by Subsequently Isolated Perfused Pancreases in the Rat

“…At the end of this period, and as shown byv Table I, the body veights of VMH-lesioned animals were identical to those of conitrols, although total carcass lipicl contenit was significantly inereased in VMIH-lesioned rats when compared with controls. Because diagnosis of successful lesionis of the VMH area could no Hi pothalamus ancd Inisulini or Glucagoni Secretion Table I, adequate lesions of the VMH could be determined, in such animals that were never hyperphagic, by the observations of consistent increases in both plasma insulin and urea levels (the latter observation has been previously reported [26,29,30]), and decrease in glycemia. The first two criteria were most reliable and were used to decide which VMHlesioned rats could be used for pancreas perfusion.…”

Nutritional Adequacy, Nutrient Availability and Needs

“…Indeed, it increases the amount of incoming nutrients, further stimulating insulin secretion; it can, therefore, be viewed as an aggravation factor (Martin et al, 1974). Much data are available, however, to show that obesity can occur in the absence of hyperphagia and that, under those conditions, increased plasma insulin levels are major determinants of obesity (Bernardis et al, 1975;Hustvedt et al, 1976). One should mention that in several species, in the genetically obese (fa/fa) rats in particular, plasma growth hormone levels are decreased as welle As this hormone is long-acting and lipolytic, its absence would, of course, further favour obesity (Martin & Jeanrenaud, 1983) •…”