Neuropeptide Y (NPY) is a potent central appetite stimulant whose concentrations rise markedly in hypothalamic appetite-regulating regions in food-deprived rats. To determine whether increased energy expenditure also affects hypothalamic NPY, we studied the effects of intense physical exercise in rats (n = 10) running voluntarily on a large-diameter exercise wheel. Running was initiated by restricting food intake but stabilized at an average of 8 km/day when food intake was matched to that in 11 nonexercised, freely fed controls [23.9 +/- 1.9 (SE) g/day vs. 24.7 +/- 1.3 g/day; P > 0.5]. Running expended approximately 40% of daily energy intake, and weight gain was significantly inhibited. A separate group (n = 10) of nonexercised rats was food restricted (approximately 15 g/day) to match the weights of the exercised rats. The rats were killed after 40 days, when both experimental groups weighed 30% less than controls (P < 0.01). Hypothalamic NPY concentrations showed significant (P < 0.01) increases of 30-70% in specific regions (arcuate and dorsomedial nuclei and medial preoptic and lateral hypothalamic areas) in both the running and food-restricted groups, compared with controls. There were no significant differences between the two experimental groups in NPY concentrations in any hypothalamic region. These findings suggest that negative energy balance, whether caused by reduced energy intake or increased expenditure, increases hypothalamic NPYergic activity. As NPY acts on the hypothalamus to increase body weight, these data support the postulated homeostatic role of NPY in maintaining nutritional state.
The JCR: LA-corpulent rat Is an obese, hyperlipidemic, hyperinsullnemlc strain that Is atherosclerosis-prone and develops myocardlal lesions. The hyperllpldemla Is due to elevated plasma levels of a large relatively triglycerlde-rich very low density lipoprotein (VLDL). Both corpulent and lean male and female rats were studied. Postheparln llpid clearance and apparent hepatic secretion rate after Triton WR1339 Inhibition of lipoproteln llpase were determined. The concentrations of cholesterol and cholesteryl esters were not significantly altered by either treatment TrlglycerIdes showed rapid postheparln clearance In corpulent rats. The apparent hepatic secretion rate was markedly higher In corpulent male rats than In lean male rats, and the rate in corpulent females was again higher, reflecting the higher serum trlglyceride concentrations In corpulent female rats. The relative secretion rate of C 4 8 trlglycerlde molecular species was lower than that of the C: 50 to C: 56 species, while the postheparln clearance of C 4 8 trlglycerlde molecular species was impaired compared to the C: 50 species and those with higher carbon numbers. This effect was more marked In the male than In the female corpulent rats. The results Indicate that VLDL hyperllpldemia In the corpulent rat Is due to hepatic hypersecretlon of VLDL and not to a defect in lipoproteln llpase. Further, the atherogenesls that Is characteristic of the corpulent male rat may be related to the differential metabolism of fatty acids. (Arteriosclerosis 9:869-876, November/December 1989) T he JCR: L A-corpulent rat incorporates the corpulent (cp) gene isolated by Koletsky. 1^ The original strain was derived from a cross of the spontaneously hypertensive (SHR) and Sprague-Dawley rat strains and was hypertensive, hyperlipidemic, and prone to a fulminant atherosclerosis. Hansen 3 incorporated the cp gene into two inbred strains, the SHR/N and the LA/N. Repeated backcrosses (more than 12 times) were made to the parent strains to give two congenic strains. Rats that are homozygous for the cp gene (cp/cp) are obese, while rats that are heterozygous (cp/+) or homozygous normal (+/+) are lean and indistinguishable from the parent strain. The LA/N-cp strain has been described by Elwood et al. 4 and studied as a model for obesity and the effects of high sugar intake. The SHR/N-cp rat is highly sensitive to dietary sucrose and is regarded as a model for the study of obesity and insulin resistance.
5In the course of the development of the LA/N-cp congenic strain, breeding stock from the fifth backcross was used to establish a colony in our laboratories. This colony differs from the fully congenic LA/N-cp and has recently been designated JCR: LA-cp. We have described this strain in previous publications.6 ' 7 The cp/cp male rats spontaneously develop both atherosclerotic and myocarFrom the Departments of Surgery and Pathology, University of Alberta, Edmonton, Alberta, and the Department of Biochemistry, Dalhousie University, Halifax, Nova Scotia, Canada.This work was supp...
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