Abstract

Daily restricted access to food leads to the development of food anticipatory activity and metabolism, which depends upon an as yet unidentified food-entrainable oscillator(s). A premeal anticipatory peak in circulating hormones, including corticosterone is also elicited by daily restricted feeding. High-fat feeding is associated with elevated levels of corticosterone with disrupted circadian rhythms and a failure to develop robust meal anticipation. It is not clear whether the disrupted corticosterone rhythm, resulting from high-fat feeding contributes to attenuated meal anticipation in high-fat fed rats. Our aim was to better characterize meal anticipation in rats fed a low- or high-fat diet, and to better understand the role of corticosterone in this process. To this end, we utilized behavioral observations, hypothalamic c-Fos expression, and indirect calorimetry to assess meal entrainment. We also used the glucocorticoid receptor antagonist, RU486, to dissect out the role of corticosterone in meal anticipation in rats given daily access to a meal with different fat content. Restricted access to a low-fat diet led to robust meal anticipation, as well as entrainment of hypothalamic c-Fos expression, metabolism, and circulating corticosterone. These measures were significantly attenuated in response to a high-fat diet, and animals on this diet exhibited a postanticipatory rise in corticosterone. Interestingly, antagonism of glucocorticoid activity using RU486 attenuated meal anticipation in low-fat fed rats, but promoted meal anticipation in high-fat-fed rats. These findings suggest an important role for corticosterone in the regulation of meal anticipation in a manner dependent upon dietary fat content.

Highlights

  • CIRCADIAN RHYTHMS IN BEHAVIOR and physiology are generated by the master circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, as well as extraSCN circadian oscillators present in other neural and peripheral tissues [7, 17, 22, 27, 39]

  • The current study shows that attenuated food-anticipatory activity (FAA) seen in rats fed a high-fat diet is associated with altered expression of c-Fos in the DMH compacta (DMHc), paraventricular hypothalamus (PVH), and SCN

  • The daily profile of corticosterone was changed in HFF-Restricted feeding (RF) rats, with a large rise occurring during the postanticipatory period

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Summary

Introduction

CIRCADIAN RHYTHMS IN BEHAVIOR and physiology are generated by the master circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, as well as extraSCN circadian oscillators present in other neural and peripheral tissues [7, 17, 22, 27, 39]. In nocturnal rodents housed under light-dark conditions, corticosterone levels peak near the onset of night, suggesting corticosterone has a role in night phase activity when nocturnal animals become most active and consume the majority of their food [12, 66, 69]. This late-day rise in corticosterone provides negative feedback to the paraventricular hypothalamus (PVH), where it acts to decrease corticotrophin-releasing factor production, and corticosterone itself [13, 66]. While corticosterone is likely to be important for FAA [19], high basal levels of this hormone may impair the development and/or expression of FAA in high-fat fed rats

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