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Autophagic Clearance of Lipid Droplets Alters Metabolic Phenotypes in a Genetic Obesity–Diabetes Mouse Model

Phenomics 2023年第2期3卷 119-129页

作者： Ningxie Chen Boxun Lu Yuhua Fu State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science School of Life SciencesFudan UniversityShanghai 200438China

Lipid droplets(LDs)are intracellular organelles that store neutral lipids,and their aberrant accumulation is associated with many diseases including metabolic disorders such as obesity and ***,the potential pathological contribu-tions of LDs in these diseases are unclear,likely due to a lack of chemical biology tools to clear *** recently developed LD-clearance small molecule compounds,Lipid Droplets·AuTophagy TEthering Compounds(LD·attecs),that are able to induce autophagic clearance of LDs in cells and in the liver of db/db(C57BL/6J Leprdb/Leprdb)mouse model,which is a widely used genetic model for obesity–***,the potential effects on the metabolic phenotype remain to be ***,using the metabolic cage assay and the blood glucose assay,we performed phenotypic characteriza-tion of the effects of the autophagic degradation of LDs by LD·attecs in the db/db mouse *** study reveals that LD·attecs increased the oxygen uptake of mice and the release of carbon dioxide,enhanced the heat production of animals,partially enhanced the exercise during the dark phase,decreased the blood glucose level and improved insulin ***,the study characterized the metabolic phenotypes induced by LD·attecs in an obesity–diabetes mouse model,revealing novel functional impacts of autophagic clearance of LDs and providing insights into LD biology and obesity–dia-betes pathogenesis from the phenotypic perspective.

关键词： Lipid droplets Autophagy Obesity–diabetes LD attecs Targeted degradation Metabolic cages

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