PMID- 31278836
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20211204
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Linking)
VI  - 228
IP  - 2
DP  - 2020 Feb
TI  - Adipocyte-derived extracellular vesicles modulate appetite and weight through 
      mTOR signalling in the hypothalamus.
PG  - e13339
LID - 10.1111/apha.13339 [doi]
AB  - AIM: Type 2 diabetes and obesity are diseases related to surplus energy in the 
      body. Abnormal interaction between the hypothalamus and adipose tissues is a key 
      trigger of energy metabolism dysfunction. Extracellular vesicles (EVs) regulate 
      intercellular communication by transporting intracellular cargo to recipient 
      cells thereby altering the function of recipient cells. This study aimed to 
      evaluate whether adipocyte-derived EVs can act on hypothalamic neurons to 
      modulate energy intake and to identify the EV-associated non-coding RNAs. 
      METHODS: Confocal imaging was used to trace the uptake of labelled 
      adipocyte-derived exosomes by hypothalamic anorexigenic POMC neurons. The effects 
      of adipocyte-derived EVs on the mammalian target of rapamycin (mTOR) signalling 
      pathway in POMC neurons were evaluated based on mRNA and protein expression in 
      vitro using quantitative real-time PCR and western blotting. In addition, 
      adipocyte-derived EVs were injected into recipient mice, and changes in mice body 
      weight and daily food intake were monitored. The biological effects of the 
      EV-associated MALAT1 on POMC neurons were explored. RESULTS: Adipocyte-derived 
      EVs were successfully transferred into POMC neurons in vitro. Results showed that 
      adipocytes of obese mice secreted MALAT1-containing EVs, which increased appetite 
      and weight when administered to lean mice. Conversely, adipocyte-derived EVs from 
      lean mice decreased food intake and weight when administered to obese mice. 
      CONCLUSION: Adipocyte-derived EVs play important roles in mediating the 
      interaction between adipocytes and hypothalamic neurons. Adipocyte-derived EVs 
      can regulate POMC expression through the hypothalamic mTOR signalling in vivo and 
      in vitro, thereby affecting body energy intake.
CI  - (c) 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
FAU - Gao, Jie
AU  - Gao J
AD  - Department of Endocrinology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Li, Xinyu
AU  - Li X
AD  - Department of Endocrinology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Wang, You
AU  - Wang Y
AD  - National Laboratory of Biomacromolecules, CAS Center for Excellence in 
      Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 
      China.
FAU - Cao, Yan
AU  - Cao Y
AD  - Department of Endocrinology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Yao, Dengju
AU  - Yao D
AD  - Software and Microelectronics School, Harbin University of Science and 
      Technology, Harbin, China.
FAU - Sun, Lijie
AU  - Sun L
AD  - Department of Endocrinology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Qin, Lv
AU  - Qin L
AD  - Department of Endocrinology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Qiu, Hui
AU  - Qiu H
AD  - Department of Endocrinology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Zhan, Xiaorong
AU  - Zhan X
AUID- ORCID: 0000-0003-4453-0727
AD  - Department of Endocrinology, First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190727
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Acta Physiol (Oxf). 2020 Feb;228(2):e13411. PMID: 31721452
MH  - Adipocytes/*metabolism/pathology
MH  - Animals
MH  - Appetite/*physiology
MH  - Body Weight/*physiology
MH  - Brain/metabolism/pathology
MH  - Cells, Cultured
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Extracellular Vesicles/*metabolism/pathology
MH  - Hypothalamus/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/metabolism/pathology
MH  - Obesity/*metabolism/pathology
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - MALAT1
OT  - adipose tissue
OT  - extracellular vesicles (EVs)
OT  - hypothalamus
OT  - obesity
EDAT- 2019/07/07 06:00
MHDA- 2021/06/29 06:00
CRDT- 2019/07/07 06:00
PHST- 2018/11/23 00:00 [received]
PHST- 2019/06/29 00:00 [revised]
PHST- 2019/07/01 00:00 [accepted]
PHST- 2019/07/07 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2019/07/07 06:00 [entrez]
AID - 10.1111/apha.13339 [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2020 Feb;228(2):e13339. doi: 10.1111/apha.13339. Epub 2019 
      Jul 27.