PMID- 33459523
OWN - NLM
STAT- MEDLINE
DCOM- 20220112
LR  - 20220112
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 27
IP  - 4
DP  - 2021 Apr
TI  - A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role 
      by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy.
PG  - 484-496
LID - 10.1111/cns.13573 [doi]
AB  - AIMS: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series 
      of neurological complications. Previous research demonstrated that a novel 
      palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic 
      inflammation. Autophagy was important in diabetic-related neurodegeneration. The 
      aim of the present study was to investigate whether 5-PAHSA has specific 
      therapeutic effects on neurological dysfunction in diabetics, particularly with 
      regard to autophagy. METHODS: 5-PAHSA was successfully synthesized according to a 
      previously described protocol. We then carried out a series of in vitro and in 
      vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, 
      respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were 
      administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed 
      glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a 
      range of inflammatory factors. RESULTS: Although there was no significant 
      improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL 
      decreased significantly following the administration of 5-PAHSA in serum of DB/DB 
      mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was 
      suppressed in both PC12 cells and DB/DB mice following the administration of 
      5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only 
      observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the 
      concentration of ROS decreased in PC12 cells and the levels of CRP increased in 
      high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms 
      of apoptosis, other inflammatory factors, or cognition in DB/DB mice following 
      the administration of 5-PAHSA. CONCLUSION: We found that 5-PAHSA can enhance 
      autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 
      5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed 
      oxidative stress in PC12 cells, and exerted influence on lipid metabolism in 
      DB/DB mice.
CI  - (c) 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & 
      Sons Ltd.
FAU - Wang, Jian-Tao
AU  - Wang JT
AD  - Department of Geriatric Neurology of Huashan Hospital, National Clinical Research 
      Center for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Yu, Zhong-Yu
AU  - Yu ZY
AD  - Department of Geriatric Neurology of Huashan Hospital, National Clinical Research 
      Center for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Tao, Ying-Hong
AU  - Tao YH
AD  - Department of Medical Examination Center, Huashan Hospital, Fudan University, 
      Shanghai, China.
FAU - Liu, Ying-Chao
AU  - Liu YC
AD  - Department of Neurosurgery, Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
FAU - Wang, Yan-Mei
AU  - Wang YM
AD  - Department of Geriatric Neurology of Huashan Hospital, National Clinical Research 
      Center for Aging and Medicine, Fudan University, Shanghai, China.
FAU - Guo, Qi-Lin
AU  - Guo QL
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Department of Translational Neuroscience, 
      Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
FAU - Xue, Jian-Zhong
AU  - Xue JZ
AD  - Department of Neurology, Fifth Clinical Medical College of Yangzhou University, 
      Changshu Second People's Hospital of Jiangsu Province, Changshu, China.
FAU - Wen, Xiao-Hong
AU  - Wen XH
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Department of Translational Neuroscience, 
      Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
FAU - Zhang, Qian
AU  - Zhang Q
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Department of Translational Neuroscience, 
      Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
FAU - Xu, Xiao-Die
AU  - Xu XD
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Department of Translational Neuroscience, 
      Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
FAU - He, Cheng-Feng
AU  - He CF
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Department of Translational Neuroscience, 
      Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
FAU - Xue, Wen-Jiao
AU  - Xue WJ
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Department of Translational Neuroscience, 
      Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
FAU - Guo, Jing-Chun
AU  - Guo JC
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Department of Translational Neuroscience, 
      Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.
FAU - Zhou, Hou-Guang
AU  - Zhou HG
AUID- ORCID: 0000-0002-5550-1166
AD  - Department of Geriatric Neurology of Huashan Hospital, National Clinical Research 
      Center for Aging and Medicine, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210118
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (5-PAHSA)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Stearic Acids)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ulk1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects/physiology
MH  - Autophagy-Related Protein-1 Homolog/*antagonists & inhibitors/metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - PC12 Cells
MH  - Palmitic Acid/*pharmacology/therapeutic use
MH  - Phosphorylation/drug effects/physiology
MH  - Rats
MH  - Signal Transduction/drug effects/physiology
MH  - Stearic Acids/*pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
PMC - PMC7941174
OTO - NOTNLM
OT  - 5-PAHSA
OT  - autophagy
OT  - m-TOR
OT  - oxidative stress
OT  - type-2 diabetes mellitus
COIS- The authors state no potential conflicts of interest for the research, 
      authorship, and publication of this article.
EDAT- 2021/01/19 06:00
MHDA- 2022/01/13 06:00
PMCR- 2021/01/18
CRDT- 2021/01/18 08:46
PHST- 2020/03/24 00:00 [received]
PHST- 2020/12/07 00:00 [revised]
PHST- 2020/12/11 00:00 [accepted]
PHST- 2021/01/19 06:00 [pubmed]
PHST- 2022/01/13 06:00 [medline]
PHST- 2021/01/18 08:46 [entrez]
PHST- 2021/01/18 00:00 [pmc-release]
AID - CNS13573 [pii]
AID - 10.1111/cns.13573 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2021 Apr;27(4):484-496. doi: 10.1111/cns.13573. Epub 2021 Jan 
      18.