ESPE Abstracts (2014) 82 FC12.1

High-Fat Diet Rapidly Triggers Circadian De-Synchronization of Clock Genes, Neuropeptides and Inflammation Mediators in the Hypothalamus of C57BL Mice

Francisco Hernández-Nuñoa, Mariano Ruiz-Gayoa, Francisca Díazb,c, Jesús Argenteb,c & Julie A Chowenb,c


aFacultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain; bDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain; cDepartment of Pediatrics, CIBERobn Instituto Carlos III, Universidad Autonoma de Madrid, Madrid, Spain


Background: Circadian disorganization of feeding behavior evoked by high fat diet (HFD) intake is suggested to be involved in the resulting weight gain and development of associated metabolic alterations and hypothalamic inflammation.

Hypothesis: We hypothesized that this circadian alteration might be a consequence of rapid de-synchronization of different gene clusters relevant for metabolic control.

Methods: We analyzed the circadian pattern of clock (Clock, Per2), neuropeptide (Npy, Agrp, Pomc) and inflammation-related interleukin (IL1β, IL6) hypothalamic gene expression and serum metabolic factors in male C57BL mice placed on a HFD or control diet at 0600, 1200, 1800 or 2400 and killed 48 h later.

Results: HFD increased weight gain (P<0.01) and energy intake (P<0.01). Insulin levels were increased by HFD at all time-points, with leptin only being increased at 1800 and 2400. Hypothalamic clock expression decreased (P<0.01), being significant at 1800 and 2400. Per2 changed over time, with no effect of HFD. HFD reduced the orexigenic neuropeptides NPY (P<0.05) and AgRP (P<0.05) and abolished their circadian rhythm of expression. POMC expression changed over time and was unaffected by HFD. HFD also mitigated the circadian changes in IL6 (P<0.05) and IL1β (P<0.05) expression.

Conclusion: HFD rapidly modulates metabolic hormones and expression of hypothalamic neuropeptides. The loss of circadian variation in orexigenic neuropeptide expression could be associated with the observed modification in the pattern of food intake. Interestingly, the HFD-induced loss of rhythmicity in IL1β and IL6 expression levels results in these mice having more, less or similar levels of these interleukins compared to controls depending on the time of day. Thus, any eventual synchronicity between zeitgeber-related genes, food intake and inflammation is disrupted by HFD.

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