PMID- 34276557
OWN - NLM
STAT- MEDLINE
DCOM- 20211223
LR  - 20211223
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 12
DP  - 2021
TI  - LC-MS-Based Untargeted Metabolomics Reveals Early Biomarkers in STZ-Induced 
      Diabetic Rats With Cognitive Impairment.
PG  - 665309
LID - 10.3389/fendo.2021.665309 [doi]
LID - 665309
AB  - Diabetes in the elderly increases cognitive impairment, but the underlying 
      mechanisms are still far from fully understood. A non-targeted metabolomics 
      approach based on liquid chromatography-mass spectrometry (LC-MS) was performed 
      to screen out the serum biomarkers of diabetic mild cognitive impairment (DMMCI) 
      in rats. Total 48 SD rats were divided into three groups, Normal control (NC) 
      group, high-fat diet (HFD) fed group and type 2 diabetes mellitus (T2DM) group. 
      The T2DM rat model was induced by intraperitoneal administration of 
      streptozotocin (STZ, 35 mg/kg) after 6 weeks of high-fat diet (HFD) feeding. Then 
      each group was further divided into 4-week and 8-week subgroups, which were 
      calculated from the time point of T2DM rat model establishment. The novel object 
      recognition test (NORT) and the Morris water maze (MWM) method were used to 
      evaluate the cognitive deficits in all groups. Compared to the NC-8w and HFD-8w 
      groups, both NOR and MWM tests indicated significant cognitive dysfunction in the 
      T2DM-8w group, which could be used as an animal model of DMMCI. Serum was 
      ultimately collected from the inferior vena cava after laparotomy. Metabolic 
      profiling analysis was conducted using ultra high performance liquid 
      chromatography coupled with quadrupole time-of-flight mass spectrometry 
      (UPLC-Q-TOF-MS) technology. Principal component analysis (PCA) and orthogonal 
      partial least squares discriminant analysis (OPLS-DA) were used to verify the 
      stability of the model. According to variable importance in the project (VIP > 1) 
      and the p-value of t-test (P < 0.05) obtained by the OPLS-DA model, the 
      metabolites with significant differences were screened out as potential 
      biomarkers. In total, we identified 94 differentially expressed (44 up-regulated 
      and 50 down-regulated) endogenous metabolites. The 10 top up-regulated and 10 top 
      down-regulated potential biomarkers were screened according to the FDR 
      significance. These biomarkers by pathway topology analysis were primarily 
      involved in the metabolism of sphingolipid (SP) metabolism, tryptophan (Trp) 
      metabolism, Glycerophospholipid (GP) metabolism, etc. Besides, SP metabolism, Trp 
      metabolism and GP metabolism mainly belonging to the lipid metabolism showed 
      marked perturbations over DMMCI and may contribute to the development of disease. 
      Taken collectively, our results revealed that T2DM could cause cognitive 
      impairment by affecting a variety of metabolic pathways especially lipid 
      metabolism. Besides, serum PE, PC, L-Trp, and S1P may be used as the most 
      critical biomarkers for the early diagnosis of DMMCI.
CI  - Copyright (c) 2021 Chen, Zeng, Xiao, Zhang and Shu.
FAU - Chen, Ruijuan
AU  - Chen R
AD  - Department of Geriatrics, Second Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Zeng, Yi
AU  - Zeng Y
AD  - Department of Geriatrics, Second Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Xiao, Wenbiao
AU  - Xiao W
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha, 
      China.
FAU - Zhang, Le
AU  - Zhang L
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha, 
      China.
FAU - Shu, Yi
AU  - Shu Y
AD  - Department of Neurology, Second Xiangya Hospital, Central South University, 
      Changsha, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210630
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Biomarkers)
SB  - IM
MH  - Animals
MH  - Biomarkers/*blood
MH  - Chromatography, Liquid/*methods
MH  - Cognitive Dysfunction/*diagnosis/etiology/metabolism/pathology
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Male
MH  - *Metabolome
MH  - Principal Component Analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tandem Mass Spectrometry/*methods
PMC - PMC8278747
OTO - NOTNLM
OT  - biomarkers
OT  - diabetes mellitus (DM)
OT  - mild cognitive impairment (MCI)
OT  - serum metabolomics
OT  - streptozotocin (STZ)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/20 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/01/01
CRDT- 2021/07/19 05:52
PHST- 2021/02/16 00:00 [received]
PHST- 2021/05/31 00:00 [accepted]
PHST- 2021/07/19 05:52 [entrez]
PHST- 2021/07/20 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2021.665309 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2021 Jun 30;12:665309. doi: 
      10.3389/fendo.2021.665309. eCollection 2021.