한빛사 논문
Jiyoon Kim1,2, Hyeyon Kim3, Shin Hye Noh1, Dong Geon Jang1, Shi-Young Park4, Dongkook Min5, Hyunki Kim6, Hee-Seok Kweon7, Hoguen Kim8, Sowon Aum1, Sookyung Seo1, Cheol Soo Choi4, Hail Kim6, Jae Woo Kim5, Seok Jun Moon3, Heon Yung Gee1 & Min Goo Lee1,*
1Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.
2Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
3Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Yonsei-ro 50-1, Seodaemun-gu, Seoul 03722, Korea.
4Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, and Department of Internal Medicine, Gachon University College of Medicine, Incheon 21999, Korea.
5Department of Biochemistry and Molecular Biology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.
6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
7Center for Research Equipment, Korea Basic Science Institute, Cheongju 28119, Korea.
8Department of Pathology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea.
*Corresponding author
Abstract
The Golgi apparatus plays a central role in the intracellular transport of macromolecules. However, molecular mechanisms of Golgi-mediated lipid transport remain poorly understood. Here, we show that genetic inactivation of the Golgi-resident protein GRASP55 in mice reduces whole-body fat mass via impaired intestinal fat absorption and evokes resistance to high-fat diet induced body weight gain. Mechanistic analyses reveal that GRASP55 participates in the Golgi-mediated lipid droplet (LD) targeting of some LD-associated lipases, such as ATGL and MGL, which is required for sustained lipid supply for chylomicron assembly and secretion. Consequently, GRASP55 deficiency leads to reduced chylomicron secretion and abnormally large LD formation in intestinal epithelial cells upon exogenous lipid challenge. Notably, deletion of dGrasp in Drosophila causes similar defects of lipid accumulation in the midgut. These results highlight the importance of the Golgi complex in cellular lipid regulation, which is evolutionary conserved, and uncover potential therapeutic targets for obesity-associated diseases.
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