2. Academic Validation
  3. Liver governs adipose remodelling via extracellular vesicles in response to lipid overload

Liver governs adipose remodelling via extracellular vesicles in response to lipid overload

  • Nat Commun. 2020 Feb 5;11(1):719. doi: 10.1038/s41467-020-14450-6.
Yue Zhao 1 2,  Meng-Fei Zhao 1,  Shan Jiang 1,  Jing Wu 1 3,  Jia Liu 1,  Xian-Wen Yuan 1 2,  Di Shen 1,  Jing-Zi Zhang 1,  Nan Zhou 2,  Jian He 2,  Lei Fang 4 5,  Xi-Tai Sun 6,  Bin Xue 7 8,  Chao-Jun Li 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University & Model Animal Research Center, Nanjing University, Nanjing, 210093, China.
  • 2 MOE Key Laboratory of Model Animals for Disease Study, Department of Hepatobiliary Surgery & Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210093, China.
  • 3 Core Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University & Model Animal Research Center, Nanjing University, Nanjing, 210093, China. njfanglei@nju.edu.cn.
  • 5 MOE Key Laboratory of Model Animals for Disease Study, Department of Hepatobiliary Surgery & Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210093, China. njfanglei@nju.edu.cn.
  • 6 MOE Key Laboratory of Model Animals for Disease Study, Department of Hepatobiliary Surgery & Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210093, China. sunxitai@vip.qq.com.
  • 7 Core Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China. xuebin@njmu.edu.cn.
  • 8 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. xuebin@njmu.edu.cn.
  • 9 State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University & Model Animal Research Center, Nanjing University, Nanjing, 210093, China. licj@nju.edu.cn.
  • 10 MOE Key Laboratory of Model Animals for Disease Study, Department of Hepatobiliary Surgery & Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210093, China. licj@nju.edu.cn.
PMID: 32024826 DOI: 10.1038/s41467-020-14450-6
Abstract

Lipid overload results in lipid redistribution among metabolic organs such as liver, adipose, and muscle; therefore, the interplay between liver and other organs is important to maintain lipid homeostasis. Here, we show that liver responds to lipid overload first and sends hepatocyte-derived extracellular vesicles (EVs) targeting adipocytes to regulate adipogenesis and lipogenesis. Geranylgeranyl diphosphate synthase (Ggpps) expression in liver is enhanced by lipid overload and regulates EV secretion through Rab27A geranylgeranylation. Consistently, liver-specific Ggpps deficient mice have reduced fat adipose deposition. The levels of several EV-derived miRNAs in the plasma of non-alcoholic fatty liver disease (NAFLD) patients are positively correlated with body mass index (BMI), and these miRNAs enhance adipocyte lipid accumulation. Thus, we highlight an inter-organ mechanism whereby the liver senses different metabolic states and sends corresponding signals to remodel adipose tissue to adapt to metabolic changes in response to lipid overload.

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