High-fat diet rapidly triggers circadian de-synchronization of clock genes, neuropeptides and inflammation mediators in the hypothalamus of C57BL mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 708-722-Obesity: Response to Interventions
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-715
Francisco Hernández-Nuño*1, Paula Stucchi1, Nuria Del Olmo1, Esther de la Fuente-Martín2, Francisca Diaz2, Jesús Argente3, Julie Ann Chowen2 and Mariano Ruiz-Gayo4
1Universidad CEU-San Pablo, Madrid, Spain, 2Hospital Niño Jesús. CIBERobn Instituto Carlos III, Madrid, Spain, 3Hospital Niño Jesus-UAM, CIBERobn Instituto Carlos III, Madrid, Spain, 4Universidad CEU - San Pablo, Madrid, Spain
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. We hypothesized that this circadian alteration might be a consequence of rapid de-synchronization of different gene clusters relevant for metabolic control. We have analyzed the circadian pattern of expression of clock (clock, per2), neuropeptide (NPY, AGRP, POMC) and inflammation-related interleukin (IL-1β, IL-6) genes in the hypothalamus of C57BL mice placed on a HFD or control diet at 6 am, 12 am, 6 pm or 12 pm and killed 48 h later. The effect on clock gene expression in the prefrontal cortex and white adipose tissue (visceral and subcutaneous) was also measured.

In the hypothalamus 48h HFD triggered the following changes: i) amplified the decrease in clock expression between 6am and 6pm with no effect on per2 expression, ii) abolished the circadian rhythm of the orexigenic neuropeptides NPY (p<0.05) and AGRP (p<0.05), but had no effect on POMC expression, and iii) mitigated the circadian changes in IL-6 (p<0.05) and IL-1β (p<0.05) expression. In the prefrontal cortex, HFD abolished clock expression rhythmicity (p<0.05). In contrast, per2rhythmicity was affected in both prefrontal cortex (p<0.05) and visceral adipose tissue (p<0.05).  

Our data show that HFD rapidly affects clock and/or per2 gene expression in diverse tissues. In the hypothalamus these changes concur with loss of circadian variation in orexigenic neuropeptide expression, which could be associated with the observed modification in the pattern of food intake. Interestingly, the HFD-induced loss of rhythmicity in IL-1β and IL-6 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. The eventual consequences of this de-synchronization in terms of energy metabolism regulation remain to be elucidated.

Nothing to Disclose: FH, PS, ND, ED, FD, JA, JAC, MR

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Funding: BFU2012-35353, BFU2011-27492, FIS PI10-00747.