Aging and Chronic Disease
Mammalian circadian rhythms are dictated by solar signals transmitted to the hypothalamic suprachaismatic nucleus (SCN). Although the SCN is the central clock for circadian rhythms, molecular clocks are found in every cell and are composed of the core clock proteins BMAL1, CLOCK/NPAS2, Period (Per) and Cryptochrome (Cry). Disruptions in the core clock occur in peripheral tissues after Western diet (WD) feeding and contribute to WD-induced metabolic disease. The mammalian center of memory, the hippocampus, is also sensitive to WD-induced dysfunction, but whether the WD disrupts the hippocampal core clock is not known. The present research explores this gap in our knowledge by examining hippocampal core clock rhythmicity in a mouse model of WD-induced obesity.
Mice were maintained on either standard rodent chow with tap water or a 45%/kcal fat WD with a 4% sugar solution (WD+S). Diurnal metabolic rhythms were collected for 24 h in metabolic cages during the 16th week of diet exposure. Livers, hypothalami and hippocampi were then collected at 4-h increments over 24 h. mRNA expression was measured using RT-qPCR and assessed by cosinor-based rhythmometry.
Results : WD+S feeding significantly increased body weight and normalized liver weight (p< 0.001) and significantly dampened diurnal rhythms of whole-body metabolism (p< 0.05). As expected, the WD+S also induced significant alterations in the hepatic rhythmicity of bmal1 and cry1 expression (p< 0.05). In line with previous findings, the rhythm of the hypothalamic core clock did not significantly differ between the dietary groups. The hippocampal core clock, however, was significantly disrupted by the WD+S. Bmal1 and npas2 expression were phase shifted by 16 and 4 h, respectively, while per2 expression was significantly amplified across all measured time points in the WD+S group (p< 0.01).
WD+S feeding significantly alters the rhythmicity of core clock mRNA expression in the hippocampus. These results indicate that diet-induced disruptions of the core clock may have implications in memory diseases with significant circadian etiologies, such as Alzheimer’s disease.
Funding Sources :
Funding was provided by the Alabama Agricultural Experiment Station and the Auburn University Center for Neuroscience Initiative.