Elsevier

Neuroscience

Volume 134, Issue 3, 2005, Pages 933-946
Neuroscience

Neuroanatomy
Influence of feeding status on neuronal activity in the hypothalamus during lipopolysaccharide-induced anorexia in rats

https://doi.org/10.1016/j.neuroscience.2005.03.063Get rights and content

Abstract

Fasting attenuates disease-associated anorexia, but the mechanisms underlying this effect are not well understood. In the present study, we investigated the extent to which a 48 h fast alters hypothalamic neuronal activity in response to the anorectic effects of lipopolysaccharide in rats. Male rats were fed ad libitum or fasted, and were injected with i.p. saline or lipopolysaccharide (250μg/kg). Immunohistochemistry for Fos protein was used to visualize neuronal activity in response to lipopolysaccharide within selected hypothalamic feeding regulatory nuclei. Additionally, food intake, body weight, plasma interleukin-1 and leptin levels, and the expression of mRNA for appetite-related neuropeptides (neuropeptide Y, proopiomelanocortin and cocaine-amphetamine-regulated transcript) were measured in a time-related manner. Our data show that the pattern of lipopolysaccharide-induced Fos expression was similar in most hypothalamic nuclei whatever the feeding status. However, we observed that fasting significantly reduced lipopolysaccharide-induced Fos expression in the paraventricular nucleus, in association with an attenuated lipopolysaccharide-induced anorexia and body weight loss. Moreover, lipopolysaccharide reduced fasting-induced Fos expression in the perifornical area of the lateral hypothalamus. Lipopolysaccharide-induced circulating levels of interleukin-1 were similar across feeding status. Finally, fasting, but not lipopolysaccharide, affected circulating level of leptin and appetite-related neuropeptides expression in the arcuate nucleus. Together, our data show that fasting modulates lipopolysaccharide-induced anorexia and body weight loss in association with neural changes in specific hypothalamic nuclei.

Section snippets

Animals

Experiments were performed on 92 adult male Wistar rats (Depré, France), weighing 280–350g, that were housed individually under controlled temperature (21±2°C) and lighting conditions (12-h light/dark on from 8:00 p.m.). Animals were acclimatized to the facility and handled daily for 1 week with unrestricted access to water and food. The Animal Care and Use Committee of the University of Bordeaux I approved all protocols.

General experimental design

Rats were randomly assigned to two feeding conditions: a) ad libitum: free

Effect of feeding status on LPS-induced anorexia, body weight loss and cytokine plasma levels

In ad libitum rats, the cumulative food intake was significantly reduced by the LPS treatment (250μg/kg, ip) [P<0.01] in a time specific manner [P<0.01] with an interaction with the two factors [P<0.01] (Fig. 1A). Interestingly, food intake was dependent on feeding status [P<0.01] (Fig. 1B). A 4 h LPS treatment significantly reduced food intake in both ad libitum and fasted-refed rats [P<0.01], with a trend for interaction [P<0.086] (Fig. 1B). Four hours after LPS injection, ad libitum rats ate

Discussion

The aim of our study was to investigate the effect of a 48 h fast on the inflammatory response and the hypothalamic neuronal activity in response to the anorectic effects of LPS in rats. We demonstrated for the first time that LPS-induced anorexia and body weight loss were attenuated in 48 h-fasted rats. These effects were accompanied by lower Fos expression in the PVN. Moreover, fasting-induced Fos expression in the LH was inhibited by LPS treatment. Concomitantly, fasting decreased plasma

Conclusion

We demonstrated for the first time that fasting attenuates LPS-induced anorexia and prevents weight loss. This effect is due neither to the NPY/POMC balance and the leptin level modification nor to the variation of LPS-induced proinflammatory cytokines production. However, the activation of downstream hypothalamic nuclei such as PVN and LH that are positioned to modulate the catabolic response to LPS is altered in LPS-treated fasted rat. Our findings support the hypothesis that fasting

Acknowledgments

We gratefully thank Dr. Michèle Guerre-Millo for helping us to perform plasma leptin assay, Pr. Gérard Tramu for having provided us with β-end antiserum, Jozina Broussillon and Pierrette Lafon for technical assistance, and Drs. Robert Dantzer and Jan-Pieter Konsman for their helpful comments on the manuscript.

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