MFSD2A in Type 2 Diabetes and Its Complications
4 affiliations
- 1Future Food and Agriculture Department, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China
- 2Auckland Bioengineering Institute, University of Auckland, Auckland 1142, New Zealand
- 3Department of Endocrinology, Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), 1882 Zhonghuan South Road, Jiaxing 314001, China
- 4School of Chemical Sciences, Faculty of Science, University of Auckland, Auckland 1142, New Zealand
Abstract
Type 2 diabetes mellitus (T2DM) and its vascular complications remain a leading cause of morbidity and mortality worldwide. Endothelial dysfunction is a common pathological denominator underlying diabetic microvascular and macrovascular disease. Major facilitator superfamily domain-containing protein 2A (MFSD2A) is a lysophosphatidylcholine transporter essential for blood–brain barrier integrity that also functions in the retina, liver, placenta, and kidney, participating in lipid homeostasis, inflammation resolution, and barrier maintenance. Emerging evidence links MFSD2A to diabetic complications. Its expression is reduced in the retina and kidney yet upregulated in the fatty liver, while its role in the vascular endothelium under diabetic conditions remains unexplored. In parallel, ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is implicated in diabetic vascular disease. This hypothesis-oriented narrative review examines MFSD2A structure, transport mechanisms, and tissue-specific functions, synthesises current evidence linking MFSD2A to diabetic complications, critically evaluates whether MFSD2A-mediated lipid transport modulates endothelial ferroptosis sensitivity, and identifies key knowledge gaps and therapeutic opportunities. This review identifies that MFSD2A is dysregulated in a tissue-specific pattern in diabetes and finds that the interplay between MFSD2A-mediated DHA transport and endothelial ferroptosis sensitivity represents a critical knowledge gap that is tractable through the tissue-specific, conditionally testable framework developed in this review.
Related
- Sphingolipid Dysregulation in Type 2 Diabetes and Its Microvascular Complications
- Mitochondrial Dynamics in Diabetes Mellitus and Its Complications: Mechanisms, Pathological Roles, and Therapeutic Implications.
- Exercise-Mediated Regulation of Pyroptosis in Diabetes and Its Complications: Molecular Mechanisms and Translational Perspectives
- Increased Plasma Endogenous Ethanol Correlates with and Discriminates Against Microvascular Complications in Type-2 Diabetic Traditionally Alcohol-Abstinent Saudi Patients: A Biomarker Cross-Sectional Analysis
- Association Between Glycemic Variability and Bone Turnover and the Sema3A Signaling Pathway in Postmenopausal Women with Type 2 Diabetes Mellitus
BibTeX
@article{jin2026mfsd2a,
title = {{MFSD2A in Type 2 Diabetes and Its Complications}},
author = {Shanshan Jin and Zhiyu Zhao and Yu Feng and Qiang Cai and Wilson Wai Cheung and Ying Xu and Ji He and Mingcong Fan and Arthur Yuanze Sun and Qiang Zhou and Jun Lu},
journal = {Biomolecules},
year = {2026},
month = nov,
doi = {10.3390/biom16111592},
url = {https://www.mdpi.com/2218-273X/16/11/1592},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MFSD2A in Type 2 Diabetes and Its Complications
AU - Shanshan Jin
AU - Zhiyu Zhao
AU - Yu Feng
AU - Qiang Cai
AU - Wilson Wai Cheung
AU - Ying Xu
AU - Ji He
AU - Mingcong Fan
AU - Arthur Yuanze Sun
AU - Qiang Zhou
AU - Jun Lu
PY - 2026
DA - 2026/11/02
JO - Biomolecules
DO - 10.3390/biom16111592
UR - https://www.mdpi.com/2218-273X/16/11/1592
AB - Type 2 diabetes mellitus (T2DM) and its vascular complications remain a leading cause of morbidity and mortality worldwide. Endothelial dysfunction is a common pathological denominator underlying diabetic microvascular and macrovascular disease. Major facilitator superfamily domain-containing protein 2A (MFSD2A) is a lysophosphatidylcholine transporter essential for blood–brain barrier integrity that also functions in the retina, liver, placenta, and kidney, participating in lipid homeostasis, inflammation resolution, and barrier maintenance. Emerging evidence links MFSD2A to diabetic complications. Its expression is reduced in the retina and kidney yet upregulated in the fatty liver, while its role in the vascular endothelium under diabetic conditions remains unexplored. In parallel, ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is implicated in diabetic vascular disease. This hypothesis-oriented narrative review examines MFSD2A structure, transport mechanisms, and tissue-specific functions, synthesises current evidence linking MFSD2A to diabetic complications, critically evaluates whether MFSD2A-mediated lipid transport modulates endothelial ferroptosis sensitivity, and identifies key knowledge gaps and therapeutic opportunities. This review identifies that MFSD2A is dysregulated in a tissue-specific pattern in diabetes and finds that the interplay between MFSD2A-mediated DHA transport and endothelial ferroptosis sensitivity represents a critical knowledge gap that is tractable through the tissue-specific, conditionally testable framework developed in this review.
SN - 2218-273X
ER -