論文 - 詳細
| RRC ID | 55030 |
|---|---|
| 著者 | Sasako T, Ohsugi M, Kubota N, Itoh S, Okazaki Y, Terai A, Kubota T, Yamashita S, Nakatsukasa K, Kamura T, Iwayama K, Tokuyama K, Kiyonari H, Furuta Y, Shibahara J, Fukayama M, Enooku K, Okushin K, Tsutsumi T, Tateishi R, Tobe K, Asahara H, Koike K, Kadowaki T, Ueki K. |
| タイトル | Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism. |
| ジャーナル | Nat Commun |
| Abstract |
Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker. |
| 巻・号 | 10(1) |
| ページ | 947 |
| 公開日 | 2019-2-27 |
| DOI | 10.1038/s41467-019-08591-6 |
| PII | 10.1038/s41467-019-08591-6 |
| PMID | 30814508 |
| PMC | PMC6393527 |
| MeSH | Animals Diabetes Mellitus / genetics Diabetes Mellitus / metabolism Diabetes Mellitus, Experimental / genetics Diabetes Mellitus, Experimental / metabolism Eating Endoplasmic Reticulum Stress* Gene Knockdown Techniques Glucose Intolerance Humans Insulin Resistance Lipid Metabolism Liver / metabolism* Male Membrane Proteins / antagonists & inhibitors Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Inbred C57BL Mice, Obese Middle Aged Non-alcoholic Fatty Liver Disease / genetics Non-alcoholic Fatty Liver Disease / metabolism Obesity / genetics Obesity / metabolism |
| IF | 11.878 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | MSM Mouse BAC clone (RDB04214) MSMg01-540H18 |