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

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

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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(Rab1 8 AKO)mice had a decreased volume ratio of SAT to VAT compared with wild-type mice.When subjected to high-fat diet(HFD),Rab1 8 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 Rab18 AKO mice had a moderate increase without ER stress stimulation.Rab18 AKO mice developed insulin resistance and systematic in-flammation.Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart mice.Furthermore,Rab1 8-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,in-dicating the involvement of Rab18 in alleviating lipid toxicity.Rab1 8 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.

Rab18subcutaneous adipose tissue(SAT)metabolically healthy obesity(MHO)lipotoxicityER stressectopic lipid storageLD-ER contact

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

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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

Shanghai Qi Zhi Institute,Shanghai 200232,China

Shanghai Key Laboratory of Metabolic Remodeling and Health,Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200438,China

Tianjian Laboratory of Advanced Biomedical Sciences,Zhengzhou University,Zhengzhou 450001,China

Department of Physiology,School of Basic Medical Sciences,Gannan Medical University,Ganzhou 341000,China

Department of Endocrinology and Metabolism,Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital,Shanghai 200025,China

Center for Endocrine Metabolism and Immune Diseases,Beijing Luhe Hospital,Capital Medical University,Beijing 101149,China

Beijing Key Laboratory of Diabetes Research and Care,Beijing 101149,China

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaLingang Laboratory

2018YFA05069012019YFA08017012022YFA08065029225430892157107LG-QS-202204-06

2024

10.1007/s11427-023-2367-9

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(6)
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