Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

Leah Macdonald, Morgan E Radler, Antonio G Paolini, Stephen P Kent

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50 Citations (Scopus)


Calorie restriction (CR) has been demonstrated to alter cytokine levels; however, its potential to modify sickness behavior (fever, anorexia, cachexia) has not. The effect of CR on sickness behavior was examined in male C57BL/6J mice fed ad libitum or restricted 25 (CR25 ) or restricted 50 (CR50 ) in food intake for 28 days and injected with 50 ?g/kg of LPS on day 29. Changes in body temperature, locomotor activity, body weight, and food intake were determined. A separate cohort of mice were fed ad libitum or CR50 for 28 days, and hypothalamic mRNA expression of inhibitory factor ?B-a (I?B-a), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), suppressor of cytokine signaling 3 (SOCS3), IL-10, neuropeptide Y (NPY), leptin, proopiomelanocortin (POMC), and corticotrophin-releasing hormone (CRH) were determined at 0, 2, and 4 h post-LPS. CR50 mice did not develop fevers, whereas the CR25 mice displayed a fever shorter in duration but with the same peak as the controls. Both CR25 and CR50 mice showed no sign of anorexia and reduced cachexia after LPS administration. Hypothalamic mRNA expression of NPY and CRH were both increased by severalfold in CR50 animals preinjection compared with controls. The CR50 mice did not demonstrate the expected rise in hypothalamic mRNA expression of COX-2, microsomal prostaglandin E synthase-1, POMC, or CRH 2 h post-LPS, and leptin expression was decreased at this time point. Increases in SOCS3, IL-10, and I?B-a expression in CR50 animals were enhanced compared with ad libitum-fed controls at 4 h post-LPS. CR results in a suppression of sickness behavior in a dose-dependent manner, which may be due to CR attenuating proinflammatory pathways and enhancing anti-inflammatory pathways.
Original languageEnglish
Pages (from-to)R172 - R184
Number of pages13
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number1
Publication statusPublished - 2011
Externally publishedYes

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