Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes

Keinan Omer; Valentine Joseph M.; Xiao Haopeng; Mahata Sushil K.; Reilly Shannon M.; Abu-Odeh Mohammad; Deluca Julia H.; Dadpey Benyamin; Cho Leslie; Pan Austin; Yu Ruth T.; Dai Yang; Liddle Christopher; Downes Michael; Evans Ronald M.; Lusis Aldons J.; Laakso Markku; Chouchani Edward T.; Ryden Mikael; Saltiel Alan R.

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Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes

机译：糖原代谢将葡萄糖稳态链接到脂肪细胞中的热生成

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Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1)(1,2). Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic beta-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels in beige adipocytes, attenuating UCP1 expression and responsiveness to cold or beta-adrenergic receptor-stimulated weight loss in obese mice. Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines, and that glycogen turnover is required to produce reactive oxygen species leading to the activation of p38 MAPK, which drives UCP1 expression. Thus, glycogen has a key regulatory role in adipocytes, linking glucose metabolism to thermogenesis.

机译：adipocytes通过持续的蛋白质1（UCP1）（1,2）的持续表达，增加能量消耗的延长交感神经。在这里，我们报告说，CateCholamines对糖原代谢的调节对于UCP1表达至关重要。慢性β-肾上腺素能活化导致表达UCP1的脂肪细胞中的糖原积累增加。脂肪细胞特异性缺失支架蛋白质，靶向糖原（PTG）的蛋白质，降低了米色脂肪细胞的糖原水平，衰减UCP1表达和对肥胖或β-肾上腺素能受体刺激的体重减轻在肥胖小鼠中的体重减轻。出乎意料地，我们观察到糖原合成和降解响应于儿茶酚胺而增加，并且需要糖原转换来产生导致P38 MAPK的活化的活性氧物质，其驱动UCP1表达。因此，糖原在脂肪细胞中具有关键的调节作用，将葡萄糖代谢与热生成联系起来。

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《Nature》 |2021年第7884期|296-301|共6页
作者
Keinan Omer; Valentine Joseph M.; Xiao Haopeng; Mahata Sushil K.; Reilly Shannon M.; Abu-Odeh Mohammad; Deluca Julia H.; Dadpey Benyamin; Cho Leslie; Pan Austin; Yu Ruth T.; Dai Yang; Liddle Christopher; Downes Michael; Evans Ronald M.; Lusis Aldons J.; Laakso Markku; Chouchani Edward T.; Ryden Mikael; Saltiel Alan R.;
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作者单位

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Dana Farber Canc Inst Dept Canc Biol Boston MA USA|Harvard Med Sch Dept Cell Biol Boston MA USA;

VA San Diego Healthcare Syst San Diego CA USA|Univ Calif San Diego San Diego CA 92103 USA;

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Univ Calif San Diego Dept Med San Diego CA 92103 USA;

Sark Inst Biol Sci Gene Express Lab La Jolla CA USA;

Sark Inst Biol Sci Gene Express Lab La Jolla CA USA;

Univ Sydney Storr Liver Ctr Westmead Inst Med Res Westmead NSW Australia|Univ Sydney Sydney Med Sch Westmead NSW Australia;

Sark Inst Biol Sci Gene Express Lab La Jolla CA USA;

Sark Inst Biol Sci Gene Express Lab La Jolla CA USA;

Univ Calif Los Angeles Dept Microbiol Immunol & Mol Genet Los Angeles CA USA;

Univ Eastern Finland Inst Clin Med Internal Med Kuopio Finland;

Dana Farber Canc Inst Dept Canc Biol Boston MA USA|Harvard Med Sch Dept Cell Biol Boston MA USA;

Karolinska Inst Karolinska Univ Hosp Dept Med H7 S-86 Stockholm Sweden;

Univ Calif San Diego Dept Med San Diego CA 92103 USA|Univ Calif San Diego Dept Pharmacol San Diego CA 92093 USA;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Adipocyte MTERF4 regulates non-shivering adaptive thermogenesis and sympathetic-dependent glucose homeostasis [J] . Castillo Anna, Vila Maria, Pedriza Ines, Biochimica et biophysica acta. Molecular basis of disease: BBA . 2019,第6期

机译：adipocyte mterf4调节非颤抖的自适应热生成和同情依赖性葡萄糖稳态
2. Glycogen storage disease type Ia: Linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism [J] . SeverS., WeinsteinD.A., WolfsdorfJ.I., Journal of clinical lipidology . 2012,第6期

机译：糖原贮积病Ia型：葡萄糖，糖原，乳酸，甘油三酸酯和尿酸代谢之间的联系
3. Hibiscus rosa sinensis Linn. Petals Modulates Glycogen Metabolism and Glucose Homeostasis Signalling Pathway in Streptozotocin-Induced Experimental Diabetes [J] . Pillai Sneha S., Mini S. Plant Foods for Human Nutrition . 2016,第1期

机译：芙蓉罗莎中华。花瓣调节链脲佐菌素诱导的实验性糖尿病患者糖原代谢和葡萄糖稳态信号通路。
4. Comprehensive phosphoproteome analysis reveals acetylation-engaged enhancement of thermogenesis in white adipocytes [C] . Hsin-Yi Chang, Kosaku Shinoda, Shingo Kajimura, ASMS Conference on Mass Spectrometry and Allied Topics . 2016

机译：综合磷脂蛋白酶体分析揭示了白色脂肪细胞中热生成的乙酰化接合的增强
5. The regulation of adipocyte glycogen metabolism by the glycogen targeting subunit PTG [D] . Jurczak, Michael J. 2008

机译：糖原靶向亚单位PTG对脂肪细胞糖原代谢的调节
6. Glucose metabolism in isolated brown adipocytes under beta-adrenergic stimulation. Quantitative contribution of glucose to total thermogenesis. [O] . D Isler, H P Hill, M K Meier 1987

机译：β-肾上腺素能刺激下孤立的棕色脂肪细胞中的葡萄糖代谢。葡萄糖对总生热的定量贡献。
7. Glycogen storage disease type Ia: Linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism [O] . Sakine, Sever, Sever, Sakine, Weinstein, David A., 2012

机译：糖原贮积病Ia型：葡萄糖，糖原，乳酸，甘油三酸酯和尿酸代谢之间的联系

Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes

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