Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders  

作　　者：Jiaming Liu Liangkui Li Dijin Xu Yuqi Li Tao Chen Yeyang Liu Yuqian Bao Yan Wang Longyan Yang Peng Li Li Xu 

机构地区：[1]State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences,Beijing Advanced Innovation Center for Structural Biology,School of Life Sciences,Tsinghua University,Beijing 100084,China [2]Shanghai Qi Zhi Institute,Shanghai 200232,China [3]Shanghai Key Laboratory of Metabolic Remodeling and Health,Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200438,China [4]Tianjian Laboratory of Advanced Biomedical Sciences,Zhengzhou University,Zhengzhou 450001,China [5]Department of Physiology,School of Basic Medical Sciences,Gannan Medical University,Ganzhou 341000,China [6]Department of Endocrinology and Metabolism,Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital,Shanghai 200025,China [7]Center for Endocrine Metabolism and Immune Diseases,Beijing Luhe Hospital,Capital Medical University,Beijing 101149,China [8]Beijing Key Laboratory of Diabetes Research and Care,Beijing 101149,China

出　　处：《Science China(Life Sciences)》2024年第6期1170-1182,共13页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Program of China(2018YFA0506901,2019YFA0801701,2022YFA0806502);the National Natural Science Foundation of China(92254308,92157107);the Lingang Laboratory(LG-QS-202204-06)。

摘　　要：Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders.These people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain elusive.Rab18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and maturation.In the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice.Rab18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype mice.When subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in SAT.In contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress stimulation.Rab18 AKO mice developed insulin resistance and systematic inflammation.Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart mice.Furthermore,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid toxicity.Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT.In conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

关 键 词：Rab18 subcutaneous adipose tissue(SAT) metabolically healthy obesity(MHO) LIPOTOXICITY ER stress ectopic lipid storage LD-ER contact 

分 类 号：R589.2[医药卫生—内分泌]