PMID- 37755291
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 2218-1989 (Print)
IS  - 2218-1989 (Electronic)
IS  - 2218-1989 (Linking)
VI  - 13
IP  - 9
DP  - 2023 Sep 14
TI  - Sex Modifies the Impact of Type 2 Diabetes Mellitus on the Murine Whole Brain 
      Metabolome.
LID - 10.3390/metabo13091012 [doi]
LID - 1012
AB  - Type 2 diabetes mellitus (T2DM) leads to the development of cardiovascular 
      diseases, cognitive impairment, and dementia. There are sex differences in the 
      presentation of T2DM and its associated complications. We sought to determine the 
      impact of sex and T2DM on the brain metabolome to gain insights into the 
      underlying mechanisms of T2DM-associated cognitive complications. Untargeted 
      metabolomic analysis was performed, using liquid chromatography-mass 
      spectrometry, on whole brain tissue from adult male and female db/db mice (a T2DM 
      model) compared to wild-type (WT) C57Bl6/J mice. Regardless of sex, T2DM 
      increased free fatty acids and decreased acylcarnitines in the brain. Sex 
      impacted the number (103 versus 65 in males and females, respectively), and types 
      of metabolites shifted by T2DM. Many choline-containing phospholipids were 
      decreased by T2DM in males. Female-specific T2DM effects included changes in 
      neuromodulatory metabolites (gamma-aminobutyric acid, 2-linoleoyl glycerol, 
      N-methylaspartic acid, and taurine). Further, there were more significantly 
      different metabolites between sexes in the T2DM condition as compared to the WT 
      controls (54 vs. 15 in T2DM and WT, respectively). T2DM alters the murine brain 
      metabolome in both sex-independent and sex-dependent manners. This work extends 
      our understanding of brain metabolic sex differences in T2DM, cognitive 
      implications, and potential sex-specific metabolic therapeutic targets.
FAU - Norman, Jennifer E
AU  - Norman JE
AUID- ORCID: 0000-0002-6903-6031
AD  - Division of Cardiovascular Medicine, Department of Internal Medicine, University 
      of California, Davis. 1 Shields Ave, Davis, CA 95616, USA.
FAU - Nuthikattu, Saivageethi
AU  - Nuthikattu S
AUID- ORCID: 0000-0002-3007-6335
AD  - Division of Cardiovascular Medicine, Department of Internal Medicine, University 
      of California, Davis. 1 Shields Ave, Davis, CA 95616, USA.
FAU - Milenkovic, Dragan
AU  - Milenkovic D
AUID- ORCID: 0000-0001-6353-0912
AD  - Department of Nutrition, University of California, Davis. 1 Shields Ave, Davis, 
      CA 95616, USA.
FAU - Villablanca, Amparo C
AU  - Villablanca AC
AD  - Division of Cardiovascular Medicine, Department of Internal Medicine, University 
      of California, Davis. 1 Shields Ave, Davis, CA 95616, USA.
LA  - eng
GR  - U24 DK092993/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20230914
PL  - Switzerland
TA  - Metabolites
JT  - Metabolites
JID - 101578790
PMC - PMC10536706
OTO - NOTNLM
OT  - brain
OT  - dementia
OT  - metabolomics
OT  - sex differences
OT  - type 2 diabetes mellitus
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study, in the collection, analyses, or interpretation of data, in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2023/09/27 12:42
MHDA- 2023/09/27 12:43
PMCR- 2023/09/14
CRDT- 2023/09/27 09:55
PHST- 2023/08/08 00:00 [received]
PHST- 2023/09/08 00:00 [revised]
PHST- 2023/09/12 00:00 [accepted]
PHST- 2023/09/27 12:43 [medline]
PHST- 2023/09/27 12:42 [pubmed]
PHST- 2023/09/27 09:55 [entrez]
PHST- 2023/09/14 00:00 [pmc-release]
AID - metabo13091012 [pii]
AID - metabolites-13-01012 [pii]
AID - 10.3390/metabo13091012 [doi]
PST - epublish
SO  - Metabolites. 2023 Sep 14;13(9):1012. doi: 10.3390/metabo13091012.