Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine, Udine, Italy.
Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine, Udine, Italy.
Tissue Cell. 2020 Oct;66:101388. doi: 10.1016/j.tice.2020.101388. Epub 2020 May 27.
Obesity is a growing threat. In recent years, the finding of functional brown adipose tissue (BAT) in adult humans implemented the studies of anti-obesity therapies based on triggering energy expenditure. The activation of BAT thermogenesis and the recruitment of brite (brown-in-white) adipocytes are under noradrenergic control. Brain-derived neurotrophic factor (BDNF), if centrally administered, enhances thermogenesis through sympathetic activation, but its direct effect on adipocytes is still unclear. The phenotypic change from fat storing to thermogenic adipocytes is recognized by the presence of multilocular lipid droplets (LDs) and fissed mitochondria that tend to surround LDs, maximizing the efficiency of fatty acid release for thermogenesis. BDNF treatment on differentiated 3T3-L1 adipocytes was compared to negative (CTRL) and positive (norepinephrine, NE) controls. BDNF significantly increased small globular mitochondria percentage (>150% CTRL), while the area surface and elongation index of branched tubules were respectively 55% and 10% lower than NE. Canonical discriminant analysis of mitochondria morphological data clearly separated differentially treated cells with 85% of the total variance. The expression of brown markers and mitochondrial dynamic genes was significantly affected by BDNF. Investigating the pathways involved in adipocyte BDNF stimulation could clarify its role in thermogenesis and its possible local regulation.
肥胖是一个日益严重的威胁。近年来，在成年人中发现功能性棕色脂肪组织（BAT），这为基于触发能量消耗的抗肥胖疗法研究提供了依据。BAT 产热的激活和 brite（白色脂肪中的棕色脂肪）脂肪细胞的募集受去甲肾上腺素能控制。脑源性神经营养因子（BDNF）如果在中枢给药，可通过交感神经激活增强产热，但它对脂肪细胞的直接作用仍不清楚。从储存脂肪到产热脂肪细胞的表型变化通过多泡脂质滴（LDs）的存在和分裂的线粒体来识别，这些线粒体倾向于围绕 LDs，从而最大限度地提高脂肪酸释放用于产热的效率。将 BDNF 处理与阴性（CTRL）和阳性（去甲肾上腺素，NE）对照比较在分化的 3T3-L1 脂肪细胞上进行。BDNF 显著增加了小而圆的线粒体百分比（>CTRL 的 150％），而分支小管的面积和伸长指数分别比 NE 低 55％和 10％。线粒体形态数据的典型判别分析清楚地区分了具有 85％总方差的差异处理细胞。BDNF 显著影响棕色标记物和线粒体动态基因的表达。研究脂肪细胞 BDNF 刺激涉及的途径可以阐明其在产热中的作用及其可能的局部调节。
