小柯机器人

美国加州大学圣迭戈分校Alan R. Saltiel研究小组发现，糖原代谢将脂肪细胞中的葡萄糖稳态与产热联系起来。该项研究成果于2021年10月27日在线发表在《自然》杂志上。

研究人员发现，儿茶酚胺的糖原代谢调节对解偶联蛋白1（UCP1）的表达至关重要。慢性β-肾上腺素激活导致表达UCP1的脂肪细胞中糖原积累增加。脂肪细胞特异性地删除一个支架蛋白——蛋白靶向糖原（PTG），减少了米色脂肪细胞中的糖原水平，并减弱了UCP1的表达和对寒冷或β肾上腺素受体刺激的肥胖小鼠体重下降的反应性。

出乎意料的是，研究人员观察到糖原的合成和降解在对儿茶酚胺的反应中增加，而且糖原周转需要产生活性氧，导致p38 MAPK的激活，从而驱动UCP1的表达。因此，糖原在脂肪细胞中具有关键的调节作用，并将葡萄糖代谢与产热联系起来。

据悉，脂肪细胞通过持续表达UCP1来增加能量消耗以应对长时间的交感神经激活。

附：英文原文

Title: Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes

Author: 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.

Issue&Volume: 2021-10-27

Abstract: 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 β-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 β-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.

DOI: 10.1038/s41586-021-04019-8

Source: https://www.nature.com/articles/s41586-021-04019-8

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