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Leptin-saporin lesion of hypothalamic arcuate neurons impairs circadian feeding rhythms

Li A-J, Dinh TT, Wang Q, Wiater MF, Ritter S (2010) Leptin-saporin lesion of hypothalamic arcuate neurons impairs circadian feeding rhythms. Neuroscience 2010 Abstracts 498.6/III29. Society for Neuroscience, San Diego, CA.

Summary: To examine the role of leptin receptor-expressing neurons in the arcuate nucleus (Arc) in circadian control of spontaneous feeding and energy expenditure, we injected a novel targeted toxin, leptin conjugated to saporin (Lep-SAP) into the Arc in rats. Lep-SAP effectively lesioned Arc neurons in a leptin-receptor dependent manner, indicated by an 80% reduction of agouti gene-related protein- or melanocyte-stimulating hormone-immunoreactive neurons in Sprague Dawley rats, but not in leptin receptor deficient Zucker fa/fa rats. Food intake and metabolism were monitored 3-5 weeks after Arc Lep-SAP and control blank-saporin (B-SAP) injections using an Oxymax system. Lep-SAP rats consumed 49% of their total daily intake during the day, compared to 34% in B-SAP rats. Eatograms (feeding actograms), cosinar analysis and Chi-square periodograms of continuous feeding records failed to detect a circadian oscillation in the feeding patterns of Lep-SAP rats, but did detect significant circadian rhythms in B-SAP controls. Unlike feeding, metabolic rate, respiratory exchange ratio and locomotor activity continued to exhibit significant circadian periodicity in both groups, though dampened in amplitude in Lep-SAPs, suggesting that rhythms of feeding and metabolism may be controlled by separate mechanisms. Expression of clock-related genes (Per1 and Bmal1) in hypothalamus, liver and white fat tissue was asynchronous in Lep-SAP rats. These results suggest that leptin-receptive neurons in the Arc exert a critical influence on the circadian patterning of food intake.

Related Products: Leptin-SAP (Cat. #IT-47)

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