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首页> 外文期刊>American Journal of Physiology >Adipocyte hypertrophy is associated with lysosomal permeability both in vivo and in vitro: Role in adipose tissue inflammation
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Adipocyte hypertrophy is associated with lysosomal permeability both in vivo and in vitro: Role in adipose tissue inflammation

机译：脂肪细胞肥大与体内和体外的溶酶体通透性有关：在脂肪组织炎症中的作用

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Obesity in both humans and rodents is characterized by adipocyte hypertrophy and the presence of death adipocytes surrounded by macrophages forming "crown-like structures." However, the biochemical pathways involved in triggering adipocyte death as well as the role of death adipocytes in adipose tissue remodeling and macrophage infiltration remain poorly understood. We now show that induction of adipocyte hypertrophy by incubation of mature adipocytes with saturated fatty acids results in lysosomal destabilization and cathepsin B (ctsb), a key lysosomal cysteine protease, activation and redistribution into the cytosol. ctsb activation was required for the lysosomal permeabilization, and its inhibition protected cells against mitochondrial dysfunction. With the use of a dietary murine model of obesity, ctsb activation was detected in adipose tissue of these mice. This is an early event during weight gain that correlates with the presence of death adipocytes, and precedes macrophage infiltration of adipose tissue. Moreover, ctsb-deficient mice showed decreased lysosomal permeabilization in adipocytes and were protected against adipocyte cell death and macrophage infiltration to adipose tissue independent of body weight. These data strongly suggest that ctsb activation and lysosomal permeabilization in adipocytes are key initial events that contribute to the adipocyte cell death and macrophage infiltration into adipose tissue associated with obesity. Inhibition of ctsb activation may be a new therapeutic strategy for the treatment of obesityassociated metabolic complications.
机译：人和啮齿动物中的肥胖症的特征在于脂肪细胞肥大和存在被形成“冠状结构”的巨噬细胞包围的死亡脂肪细胞。然而，涉及触发脂肪细胞死亡的生化途径以及死亡脂肪细胞在脂肪组织重塑和巨噬细胞浸润中的作用仍知之甚少。我们现在显示，通过用饱和脂肪酸与成熟脂肪细胞一起培养来诱导脂肪细胞肥大，导致溶酶体去稳定化和组织蛋白酶B（ctsb），一种关键的溶酶体半胱氨酸蛋白酶，活化和重新分布到细胞质中。溶酶体通透性需要ctsb激活，其抑制作用可保护细胞免受线粒体功能障碍的影响。使用肥胖的饮食鼠模型，在这些小鼠的脂肪组织中检测到ctsb激活。这是体重增加期间的早期事件，其与死亡脂肪细胞的存在相关，并且先于脂肪组织的巨噬细胞浸润。此外，ctsb缺陷小鼠在脂肪细胞中显示出溶酶体通透性降低，并受到保护，可防止脂肪细胞死亡和巨噬细胞浸润到脂肪组织，而与体重无关。这些数据强烈表明，脂肪细胞中的ctsb激活和溶酶体通透性是关键的初始事件，这些事件导致脂肪细胞死亡以及巨噬细胞浸润与肥胖相关的脂肪组织。抑制ctsb激活可能是治疗肥胖相关代谢并发症的新治疗策略。

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