Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With Metformin.
amino acid, T2DM
body mass index-BMI
mass spectrometry-LC-MS/MS
metabolomics
metformin
obesity
type 2 diabete mellitus
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
10
2020
accepted:
30
12
2020
entrez:
5
3
2021
pubmed:
6
3
2021
medline:
6
3
2021
Statut:
epublish
Résumé
Metformin is widely used in the treatment of Type 2 Diabetes Mellitus (T2DM). However, it is known to have beneficial effects in many other conditions, including obesity and cancer. In this study, we aimed to investigate the metabolic effect of metformin in T2DM and its impact on obesity. A mass spectrometry (MS)-based metabolomics approach was used to analyze samples from two cohorts, including healthy lean and obese control, and lean as well as obese T2DM patients on metformin regimen in the last 6 months. The results show a clear group separation and sample clustering between the study groups due to both T2DM and metformin administration. Seventy-one metabolites were dysregulated in diabetic obese patients (30 up-regulated and 41 down-regulated), and their levels were unchanged with metformin administration. However, 30 metabolites were dysregulated (21 were up-regulated and 9 were down-regulated) and then restored to obese control levels by metformin administration in obese diabetic patients. Furthermore, in obese diabetic patients, the level of 10 metabolites was dysregulated only after metformin administration. Most of these dysregulated metabolites were dipeptides, aliphatic amino acids, nucleic acid derivatives, and urea cycle components. The metabolic pattern of 62 metabolites was persistent, and their levels were affected by neither T2DM nor metformin in obesity. Interestingly, 9 metabolites were significantly dysregulated between lean and obese cohorts due to T2DM and metformin regardless of the obesity status. These include arginine, citrulline, guanidoacetic acid, proline, alanine, taurine, 5-hydroxyindoleacetic acid, and 5-hydroxymethyluracil. Understanding the metabolic alterations taking place upon metformin treatment would shed light on possible molecular targets of metformin, especially in conditions like T2DM and obesity.
Identifiants
pubmed: 33664666
doi: 10.3389/fphar.2020.616157
pii: 616157
pmc: PMC7921791
doi:
Types de publication
Journal Article
Langues
eng
Pagination
616157Informations de copyright
Copyright © 2021 Aleidi, Dahabiyeh, Gu, Al Dubayee, Alshahrani, Benabdelkamel, Mujammami, Li, Aljada and Abdel Rahman.
Déclaration de conflit d'intérêts
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.
Références
Cell Metab. 2012 May 2;15(5):606-14
pubmed: 22560213
Regul Pept. 2010 Feb 25;160(1-3):75-80
pubmed: 19695292
Nat Rev Endocrinol. 2018 Feb;14(2):88-98
pubmed: 29219149
Front Mol Biosci. 2020 Dec 14;7:609806
pubmed: 33381523
Diabetologia. 2017 Sep;60(9):1577-1585
pubmed: 28776086
Metabolites. 2019 Nov 12;9(11):
pubmed: 31718082
Nature. 2014 Jun 26;510(7506):542-6
pubmed: 24847880
Anal Chem. 2013 Mar 19;85(6):3401-8
pubmed: 23373753
Mass Spectrom Rev. 2019 May;38(3):221-238
pubmed: 29073341
J Proteome Res. 2020 Jun 5;19(6):2346-2357
pubmed: 32312052
Ann N Y Acad Sci. 2013 May;1287:1-16
pubmed: 23659636
Metabolism. 2019 Feb;91:18-29
pubmed: 30468782
Anal Chim Acta. 2018 Sep 26;1025:141-153
pubmed: 29801603
Diabetes Care. 2012 Apr;35(4):731-7
pubmed: 22442396
Diabetes. 2016 Dec;65(12):3776-3785
pubmed: 27621107
Metabolism. 2013 Dec;62(12):1772-8
pubmed: 23953891
Nutrients. 2018 Jan 13;10(1):
pubmed: 29342866
Diabetes. 2013 Feb;62(2):639-48
pubmed: 23043162
Mol Syst Biol. 2012;8:615
pubmed: 23010998
Obes Facts. 2013;6(5):449-68
pubmed: 24135948
Sci Rep. 2016 Feb 05;6:20594
pubmed: 26846565
Front Endocrinol (Lausanne). 2017 Jan 24;8:6
pubmed: 28167928
Diabetes. 2013 May;62(5):1730-7
pubmed: 23160532
Anal Chem. 2015 Oct 6;87(19):9838-45
pubmed: 26327437
Diabetes Metab. 2019 Apr;45(2):167-174
pubmed: 29555466
Mol Cells. 2015 Jul;38(7):587-96
pubmed: 26072981
Front Endocrinol (Lausanne). 2019 May 07;10:294
pubmed: 31133988
Nutrients. 2019 May 10;11(5):
pubmed: 31083291
PLoS One. 2016 Feb 10;11(2):e0148361
pubmed: 26863521
Metabolism. 2015 Jun;64(6):720-8
pubmed: 25733201
Molecules. 2018 Jul 23;23(7):
pubmed: 30041493
Pharmaceuticals (Basel). 2019 Apr 30;12(2):
pubmed: 31052291
Metabolites. 2020 Jan 21;10(2):
pubmed: 31973046
Lancet. 2017 Jun 3;389(10085):2239-2251
pubmed: 28190580
Circulation. 2012 May 8;125(18):2222-31
pubmed: 22496159
Lancet. 1998 Sep 12;352(9131):854-65
pubmed: 9742977
Int J Mol Sci. 2019 May 18;20(10):
pubmed: 31109071
Cell Metab. 2009 Apr;9(4):311-26
pubmed: 19356713
Anal Chem. 2012 Dec 18;84(24):10723-31
pubmed: 23190334
Front Pharmacol. 2016 Jun 14;7:135
pubmed: 27378919
Nat Med. 2011 Apr;17(4):448-53
pubmed: 21423183
Diabetol Int. 2016 Aug 9;8(1):69-75
pubmed: 30603309
J Proteome Res. 2018 Apr 6;17(4):1452-1462
pubmed: 29493238
Nature. 2006 Dec 14;444(7121):840-6
pubmed: 17167471
Anal Chem. 2015 Jan 20;87(2):1306-13
pubmed: 25496403
Appl Biochem Biotechnol. 2019 May;188(1):165-184
pubmed: 30393821
Nutrition. 2001 Nov-Dec;17(11-12):934-8
pubmed: 11744344
Diabetes Care. 2016 May;39(5):833-46
pubmed: 27208380
Front Endocrinol (Lausanne). 2018 Aug 21;9:372
pubmed: 30186229
Endocrinology. 2017 May 1;158(5):1049-1063
pubmed: 28323941
Clin Sci (Lond). 2012 Mar;122(6):253-70
pubmed: 22117616
Sci Rep. 2019 May 7;9(1):7010
pubmed: 31065046
Anal Chem. 2014 May 20;86(10):4675-9
pubmed: 24766305
Obes Facts. 2017;10(5):483-492
pubmed: 29020674
Cells. 2019 Jan 14;8(1):
pubmed: 30646605
PLoS One. 2012;7(11):e49279
pubmed: 23166628
J Pharmacokinet Pharmacodyn. 2015 Oct;42(5):463-75
pubmed: 26335661
Trends Biochem Sci. 2017 Apr;42(4):274-284
pubmed: 28196646
PeerJ. 2018 Aug 31;6:e5410
pubmed: 30186675
Nat Rev Endocrinol. 2019 Oct;15(10):569-589
pubmed: 31439934
Diabetes Care. 2015 Dec;38(12):e216-7
pubmed: 26604292
Metabolomics. 2019 Jun 13;15(6):93
pubmed: 31197497
Lancet Diabetes Endocrinol. 2014 Jan;2(1):65-75
pubmed: 24622670
Diabetes Metab Syndr. 2017 Jan - Mar;11(1):73-79
pubmed: 27353549
Clin Endocrinol (Oxf). 2012 May;76(5):674-82
pubmed: 21958081