2009年10月
Ketogenic Diet Disrupts the Circadian Clock and Increases Hypofibrinolytic Risk by Inducing Expression of Plasminogen Activator Inhibitor-1
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
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- 巻
- 29
- 号
- 10
- 開始ページ
- 1571
- 終了ページ
- U418
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1161/ATVBAHA.109.190140
- 出版者・発行元
- LIPPINCOTT WILLIAMS & WILKINS
Objectives-Metabolic disorders such as diabetes and obesity are considered risk factors for cardiovascular diseases by increasing levels of blood plasminogen activator inhibitor-1 (PAI-1). Ketogenic diets (KDs) have been used as an approach to weight loss in both obese and nonobese individuals. We examined circadian changes in plasma PAI-1 and its mRNA expression levels in tissues from mice fed with a KD (KD mice), to evaluate its effects on fibrinolytic functions.
Methods and Results-Two weeks on the kDa increased plasma levels of free fatty acids and ketones accompanied by hypoglycemia in mice. Plasma PAI-1 concentrations were extremely elevated in accordance with mRNA expression levels in the heart and liver, but not in the kidneys of KD mice. Circadian expression of PAI-1 mRNA was phase-advanced for 4.7, 7.9, and 7.8 hours in the heart, kidney, and adipose tissues, respectively, as well as that of circadian genes mPer2 and DBP in KD mice, suggesting that peripheral clocks were phase-advanced by ketosis despite feeding ad libitum under a periodic light-dark cycle. The circadian clock that regulates behavioral activity rhythms was also phase-advanced, and its free-running period was significantly shortened in KD mice.
Conclusions-Our findings suggest that ketogenic status increases hypofibrinolytic risk by inducing abnormal circadian expression of PAI-1. (Arterioscler Thromb Vasc Biol. 2009; 29: 1571-1577.)
Methods and Results-Two weeks on the kDa increased plasma levels of free fatty acids and ketones accompanied by hypoglycemia in mice. Plasma PAI-1 concentrations were extremely elevated in accordance with mRNA expression levels in the heart and liver, but not in the kidneys of KD mice. Circadian expression of PAI-1 mRNA was phase-advanced for 4.7, 7.9, and 7.8 hours in the heart, kidney, and adipose tissues, respectively, as well as that of circadian genes mPer2 and DBP in KD mice, suggesting that peripheral clocks were phase-advanced by ketosis despite feeding ad libitum under a periodic light-dark cycle. The circadian clock that regulates behavioral activity rhythms was also phase-advanced, and its free-running period was significantly shortened in KD mice.
Conclusions-Our findings suggest that ketogenic status increases hypofibrinolytic risk by inducing abnormal circadian expression of PAI-1. (Arterioscler Thromb Vasc Biol. 2009; 29: 1571-1577.)
- リンク情報
- ID情報
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- DOI : 10.1161/ATVBAHA.109.190140
- ISSN : 1079-5642
- Web of Science ID : WOS:000269848600028