Lipids Alterations Associated with Metformin in Healthy Subjects: An Investigation Using Mass Spectrometry Shotgun Approach

Metformin is an orally effective insulin-sensitizing drug widely prescribed for treating type 2 diabetes mellitus (T2DM). Metformin has been reported to alter lipid metabolism. However, the molecular mechanisms behind its impact on lipid metabolism remain partially explored and understood. In the cu...

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Published in:International journal of molecular sciences Vol. 23; no. 19; p. 11478
Main Authors: Dahabiyeh, Lina A., Mujammami, Muhammad, AlMalki, Reem H., Arafat, Tawfiq, Benabdelkamel, Hicham, Alfadda, Assim A., Abdel Rahman, Anas M.
Format: Journal Article
Language:English
Published: Basel MDPI AG 01.10.2022
MDPI
Subjects:
Antidiabetics
Diabetes
Glucose
Insulin
Kinases
Lipids
Mass spectrometry
Metabolism
Metabolites
Multivariate analysis
Polycystic ovary syndrome
Scientific imaging
ISSN:1422-0067, 1661-6596, 1422-0067
Online Access:Get full text
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Summary:Metformin is an orally effective insulin-sensitizing drug widely prescribed for treating type 2 diabetes mellitus (T2DM). Metformin has been reported to alter lipid metabolism. However, the molecular mechanisms behind its impact on lipid metabolism remain partially explored and understood. In the current study, mass spectrometry-based lipid profiling was used to investigate the lipidomic changes in the serum of 26 healthy individuals after a single-dose intake of metformin. Samples were analyzed at five-time points: preadministration, before the maximum concentration of metformin (Cmax), Cmax, after Cmax, and 36 h post-administration. A total of 762 molecules were significantly altered between the five-time points. Based on a comparison between baseline level and Cmax, metformin significantly increased and decreased the level of 33 and 192 lipids, respectively (FDR ≤ 0.05 and fold change cutoff of 1.5). The altered lipids are mainly involved in arachidonic acid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism. Furthermore, several lipids acted in an opposed or similar manner to metformin levels and included fatty acyls, sterol lipids, glycerolipids, and glycerophospholipids. The significantly altered lipid species pointed to fundamental lipid signaling pathways that could be linked to the pleiotropic effects of metformin in T2DM, insulin resistance, polycystic ovary syndrome, cancer, and cardiovascular diseases.
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These authors contributed equally to this work.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231911478