دورية أكاديمية
Diet-induced loss of adipose hexokinase 2 correlates with hyperglycemia
| العنوان: | Diet-induced loss of adipose hexokinase 2 correlates with hyperglycemia |
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| المؤلفون: | Mitsugu Shimobayashi, Amandine Thomas, Sunil Shetty, Irina C Frei, Bettina K Wölnerhanssen, Diana Weissenberger, Anke Vandekeere, Mélanie Planque, Nikolaus Dietz, Danilo Ritz, Anne Christin Meyer-Gerspach, Timm Maier, Nissim Hay, Ralph Peterli, Sarah-Maria Fendt, Nicolas Rohner, Michael N Hall |
| المصدر: | eLife, Vol 12 (2023) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | obesity, glucose, lipid metabolism, adipose tissue, diabetes, selective insulin resistance, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Chronically high blood glucose (hyperglycemia) leads to diabetes and fatty liver disease. Obesity is a major risk factor for hyperglycemia, but the underlying mechanism is unknown. Here, we show that a high-fat diet (HFD) in mice causes early loss of expression of the glycolytic enzyme Hexokinase 2 (HK2) specifically in adipose tissue. Adipose-specific knockout of Hk2 reduced glucose disposal and lipogenesis and enhanced fatty acid release in adipose tissue. In a non-cell-autonomous manner, Hk2 knockout also promoted glucose production in liver. Furthermore, we observed reduced hexokinase activity in adipose tissue of obese and diabetic patients, and identified a loss-of-function mutation in the hk2 gene of naturally hyperglycemic Mexican cavefish. Mechanistically, HFD in mice led to loss of HK2 by inhibiting translation of Hk2 mRNA. Our findings identify adipose HK2 as a critical mediator of local and systemic glucose homeostasis, and suggest that obesity-induced loss of adipose HK2 is an evolutionarily conserved mechanism for the development of selective insulin resistance and thereby hyperglycemia. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/85103Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.85103 |
| الوصول الحر: | https://doaj.org/article/c1e2768af6504e0cbd38f53c60cca042Test |
| رقم الانضمام: | edsdoj.1e2768af6504e0cbd38f53c60cca042 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.85103 |