Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms

Apr 12, 2012American journal of physiology. Regulatory, integrative and comparative physiology

Leptin-sensitive neurons in the appetite control area help regulate natural feeding rhythms

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Abstract

Rats with leptin receptor-B-expressing neuron disruptions in the arcuate nucleus exhibited a 59% daytime feeding rate compared to 36% in controls.

Disruption of leptin receptor-B neurons in the arcuate nucleus led to initial hyperphagia and rapid obesity in rats.
Lep-SAP rats were arrhythmic in both light-dark and continuous dark conditions, in contrast to controls that displayed significant circadian feeding rhythms.
After approximately 8 weeks, Lep-SAP rats transitioned to a static phase of weight gain with reduced hyperphagia but maintained arrhythmic feeding in continuous light and dark.
Electrolytic lesions of the suprachiasmatic nucleus resulted in feeding arrhythmia but did not induce hyperphagia or obesity.
Findings indicate that both arcuate nucleus leptin receptor-B neurons and the suprachiasmatic nucleus are necessary for feeding rhythms aligned with light cues.

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Neural sites that interact with the suprachiasmatic nuclei (SCN) to generate rhythms of unrestricted feeding remain unknown. We used the targeted toxin, leptin conjugated to saporin (Lep-SAP), to examine the importance of leptin receptor-B (LepR-B)-expressing neurons in the arcuate nucleus (Arc) for generation of circadian feeding rhythms. Rats given Arc Lep-SAP injections were initially hyperphagic and rapidly became obese (the "dynamic phase" of weight gain). During this phase, Lep-SAP rats were arrhythmic under 12:12-h light-dark (LD) conditions, consuming 59% of their total daily intake during the daytime, compared with 36% in blank-SAP (B-SAP) controls. Lep-SAP rats were also arrhythmic in continuous dark (DD), while significant circadian feeding rhythms were detected in all B-SAP controls. Approximately 8 wk after injection, Lep-SAP rats remained obese but transitioned into a "static phase" of weight gain marked by attenuation of their hyperphagia and rate of weight gain. In this phase, Arc Lep-SAP rats exhibited circadian feeding rhythms under LD conditions, but were arrhythmic in continuous light (LL) and DD. Lep-SAP injections into the ventromedial hypothalamic nucleus did not cause hyperphagia, obesity, or arrhythmic feeding in either LD or DD. Electrolytic lesion of the SCN produced feeding arrhythmia in DD but not hyperphagia or obesity. Results suggest that both Arc Lep-SAP neurons and SCN are required for generation of feeding rhythms entrained to photic cues, while also revealing an essential role for the Arc in maintaining circadian rhythms of ad libitum feeding independent of light entrainment.

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Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms

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