细胞生物学
肥胖
膜蛋白
化学
膜
医学
生物
内科学
生物化学
作者
Ryohei Sakai,Shu Aizawa,Hyeon‐Cheol Lee,Katsunori Hase,Hiromi Fujita,Hisae Kikuchi,Yukiko Inoue,Takayoshi Inoue,Chihana Kabuta,Takehiko Yokomizo,Tadafumi Hashimoto,Keiji Wada,Tatsuo Mano,Ikuko Koyama‐Honda,Tomohiro Kabuta
出处
期刊:Cell Reports
[Cell Press]
日期:2025-06-01
卷期号:44 (6): 115829-115829
标识
DOI:10.1016/j.celrep.2025.115829
摘要
Lifestyle diseases, such as obesity, diabetes, and metabolic syndrome, are leading health problems, most of which are related to abnormal lipid metabolism. Lysosomes can degrade lipid droplets (LDs) via microautophagy, but the regulatory factors and physiological significance of this process are not fully understood. Here, we report the molecular mechanism and pathophysiological roles of microlipophagy, regulated by the lysosomal membrane protein LAMP2B. Our study reveals that LAMP2B interacts with phosphatidic acid, facilitating lysosomal-LD interactions and enhancing lipid hydrolysis via microlipophagy depending on endosomal sorting complexes required for transport. Correlative light and electron microscopy demonstrates direct LD uptake into lysosomes at contact sites. Moreover, LAMP2B overexpression in mice prevents high-fat diet-induced obesity, insulin resistance, and adipose tissue inflammation; liver lipidomics analysis suggests enhanced triacylglycerol hydrolysis. Overall, the findings of this study elucidate the mechanism of microlipophagy, which could be promising for the treatment of obesity and related disorders.
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