Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:417

Article

Genzer, Yoni¹  Dadon, Maayan¹  Burg, Chen¹  Chapnik, Nava¹  Froy, Oren¹ 

[1] Hebrew Univ Jerusalem, Inst Biochem Food Sci & Nutr, Robert H Smith Fac Agr Food & Environm, IL-76100 Rehovot, Israel

关键词: Ketogenic diet;    Metabolism;    Clock;    Circadian;    Delay;   

DOI  :  10.1016/j.mce.2015.09.012

来源: Elsevier

【 摘 要 】

Ketogenic diet (KD) is used for weight loss or to treat epilepsy. KD leads to liver AMP-activated protein kinase (AMPK) activation, which would be expected to inhibit gluconeogenesis. However, KD leads to increased hepatic glucose output. As AMPK and its active phosphorylated form (pAMPK) show circadian oscillation, this discrepancy could stem from wrong-time-of-day sampling. The effect of KD was tested on mouse clock gene expression, AMPK, mTOR, SIRT1 and locomotor activity for 2 months and compared to low-fat diet (LED). KD led to 1.5-fold increased levels of blood glucose and insulin. Brain pAMPK/AMPK ratio was 40% higher under KD, whereas that in liver was not affected. KD led to 40% and 20% downregulation of the ratio of pP70S6K/P70S6K, the downstream target of mTOR, in the brain and liver, respectively. SIRT1 levels were 40% higher in the brain, but 40% lower in the liver of KD-fed mice. Clock genes showed delayed rhythms under KD. In the brain of KD-fed mice, amplitudes of clock genes were down-regulated, whereas 6-fold up-regulation was found in the liver. The metabolic state under KD indicates reduced satiety in the brain and reduced anabolism alongside increased gluconeogenesis in the liver. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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