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BMP8B 通过中枢和外周作用增加棕色脂肪组织产热。

BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions.

机构信息

Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, UK.

出版信息

Cell. 2012 May 11;149(4):871-85. doi: 10.1016/j.cell.2012.02.066.

DOI:10.1016/j.cell.2012.02.066
PMID:22579288
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3383997/
Abstract

Thermogenesis in brown adipose tissue (BAT) is fundamental to energy balance and is also relevant for humans. Bone morphogenetic proteins (BMPs) regulate adipogenesis, and, here, we describe a role for BMP8B in the direct regulation of thermogenesis. BMP8B is induced by nutritional and thermogenic factors in mature BAT, increasing the response to noradrenaline through enhanced p38MAPK/CREB signaling and increased lipase activity. Bmp8b(-/-) mice exhibit impaired thermogenesis and reduced metabolic rate, causing weight gain despite hypophagia. BMP8B is also expressed in the hypothalamus, and Bmp8b(-/-) mice display altered neuropeptide levels and reduced phosphorylation of AMP-activated protein kinase (AMPK), indicating an anorexigenic state. Central BMP8B treatment increased sympathetic activation of BAT, dependent on the status of AMPK in key hypothalamic nuclei. Our results indicate that BMP8B is a thermogenic protein that regulates energy balance in partnership with hypothalamic AMPK. BMP8B may offer a mechanism to specifically increase energy dissipation by BAT.

摘要

棕色脂肪组织（BAT）中的产热对于能量平衡至关重要，这对人类也同样相关。骨形态发生蛋白（BMPs）调节脂肪生成，在这里，我们描述了 BMP8B 在直接调节产热中的作用。BMP8B 受成熟 BAT 中的营养和产热因素诱导，通过增强 p38MAPK/CREB 信号和增加脂肪酶活性来增加对去甲肾上腺素的反应。Bmp8b(-/-) 小鼠表现出产热受损和代谢率降低，尽管摄食量减少，但体重仍会增加。BMP8B 也在下丘脑表达，Bmp8b(-/-) 小鼠显示神经肽水平改变和 AMP 激活蛋白激酶（AMPK）磷酸化减少，表明存在厌食状态。中枢 BMP8B 处理增加了 BAT 的交感神经激活，这依赖于关键下丘脑核中 AMPK 的状态。我们的结果表明，BMP8B 是一种产热蛋白，与下丘脑 AMPK 一起调节能量平衡。BMP8B 可能为通过 BAT 特异性增加能量消耗提供了一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/9d339f9923cd/figs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/848419d2d24b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/978d3c9999fb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/9726a8764584/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/32faa9e673a5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/c7cbe154fc57/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/1cfa947444cb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/74c359e5abef/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/2bdd8318e993/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/b2e679bbc391/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/f852afc3ba15/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/89cd0d0a8d0b/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/f309f10e0ff6/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/e233b4e749ec/figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/9d339f9923cd/figs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/848419d2d24b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/978d3c9999fb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/9726a8764584/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/32faa9e673a5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/c7cbe154fc57/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/1cfa947444cb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/74c359e5abef/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/2bdd8318e993/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/b2e679bbc391/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/f852afc3ba15/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/89cd0d0a8d0b/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/f309f10e0ff6/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/e233b4e749ec/figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ce/3383997/9d339f9923cd/figs6.jpg

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