title: Lipid droplet remodeling and interaction with mitochondria in mouse brown adipose tissue during cold treatment.
abstract: Brown adipose tissue (BAT) maintains animal body temperature by non-shivering thermogenesis, which is through uncoupling protein 1 (UCP1) that uncouples oxidative phosphorylation and utilizes β-oxidation of fatty acids released from triacylglycerol (TAG) in lipid droplets (LDs). Increasing BAT activity and "browning" other tissues such as white adipose tissue (WAT) can enhance the expenditure of excess stored energy, and in turn reduce prevalence of metabolic diseases. Although many studies have characterized the biology of BAT and brown adipocytes, BAT LDs especially their activation induced by cold exposure remain to be explored. We have isolated LDs from mouse interscapular BAT and characterized the full proteome using mass spectrometry. Both morphological and biochemical experiments showed that the LDs could tightly associate with mitochondria. Under cold treatment mouse BAT started expressing LD structure protein PLIN-2/ADRP and increased expression of PLIN1. Both hormone sensitive lipase (HSL) and adipose TAG lipase (ATGL) were increased in LDs. In addition, isolated BAT LDs showed increased levels of the mitochondrial protein UCP1, and prolonged cold exposure could stimulate BAT mitochondrial cristae biogenesis. These changes were in agreement with the data from transcriptional analysis. Our results provide the BAT LD proteome for the first time and show that BAT LDs facilitate heat production by coupling increasing TAG hydrolysis through recruitment of ATGL and HSL to the organelle and expression of another LD resident protein PLIN2/ADRP, as well as by tightly associating with activated mitochondria. These findings will benefit the study of BAT activation and the interaction between LDs and mitochondria.
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Jinhai
authors: J
authors: Yu
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Shuyan
authors: S
authors: Zhang
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors: Liujuan
authors: L
authors: Cui
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.
authors: Weiyi
authors: W
authors: Wang
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Huimin
authors: H
authors: Na
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Xiaotong
authors: X
authors: Zhu
authors: Department of Anesthesiology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
authors: Linghai
authors: L
authors: Li
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.
authors: Guoheng
authors: G
authors: Xu
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Fuquan
authors: F
authors: Yang
authors: Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors: Mark
authors: M
authors: Christian
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: pliu@ibp.ac.cn.
authors: Pingsheng
authors: P
authors: Liu
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D003080:Cold Temperature; D004734:Energy Metabolism; D066292:Lipid Droplets / Q000378:metabolism* / Q000648:ultrastructure; D050356:Lipid Metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics
chemical_list: D024101:Mitochondrial Proteins
keywords: BAT; Cold exposure; LDs; Mitochondria; Proteomics