Myeloid-Derived Growth Factor Alleviates Diabetic Non-Alcoholic Fatty Liver Disease by Up-Regulating ABCA1 and ABCG1 Expression via the AMPK/PPARγ/LXRα Pathway.
- 1School of Medical Informatics and Engineering, Hunan Medical College, Huaihua, Hunan Province, China.
- 2Department of Endocrinology, General Hospital of Central Theater Command, Wuhan, Hubei Province, China.
Abstract
The regulatory role of bone marrow in systemic metabolic processes remains incompletely characterized. Myeloid-derived growth factor (MYDGF) is a myeloid cell-secreted factor with emerging metabolic functions, but its action in diabetes-associated non-alcoholic fatty liver disease (DM NAFLD) is undefined. To investigate the influence of myeloid cell-derived MYDGF on DM NAFLD, both loss- and gain-of-function approaches were applied in vivo. DM NAFLD models were established in Mydgf-knockout (KO) mice, PpargΔLyz2 mice and PpargΔLyz2/KO (DKO) mice. For in vitro studies, primary Kupffer cells (KCs) were stimulated with high glucose and recombinant MYDGF (rMYDGF) and bone marrow cells (BMCs) were co-cultured with KCs via a transwell system. Protein levels related to DM NAFLD pathology and signalling pathways were quantified. In this study, we found that MYDGF was significantly downregulated in DM NAFLD mouse liver. Myeloid MYDGF deficiency exacerbated hepatic inflammation, lipogenesis, steatosis and macrophage infiltration, while reconstituting myeloid MYDGF reversed these phenotypes. rMYDGF attenuated inflammation, reduced macrophage foaming, decreased cholesterol content and increased efferocytosis. Mechanistically, MYDGF induced AMP-activated protein kinase (AMPK) phosphorylation, which subsequently activated the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) pathway in KCs and upregulated downstream ABCA1 and ABCG1 expression. These results identify the AMPK/PPARγ/LXRα-ABCA1/ABCG1 cascade as the core signalling axis mediating MYDGF's metabolic regulatory effects, which bridges the previously unrecognized functional linkage between myeloid cell function and hepatic lipid homeostasis, and explains the protective phenotype observed in MYDGF-reconstituted DM NAFLD mice. In conclusion, myeloid cell-derived MYDGF ameliorates DM NAFLD, decreases cholesterol content in macrophages and reduces lipid accumulation via the AMPK/PPARγ/LXRα pathway. MYDGF serves as a key mediator for bone marrow-liver metabolic crosstalk, indicating that the bone marrow may act as a potential endocrine target for the prevention and treatment of diabetes-related metabolic disorders.
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BibTeX
@article{chen2026myeloidderived,
title = {{Myeloid-Derived Growth Factor Alleviates Diabetic Non-Alcoholic Fatty Liver Disease by Up-Regulating ABCA1 and ABCG1 Expression via the AMPK/PPARγ/LXRα Pathway.}},
author = {Zeyu Chen and Biying Meng and Bingyi Wang and Yan Ding},
journal = {Journal of cellular and molecular medicine},
year = {2026},
month = nov,
doi = {10.1111/jcmm.71428},
url = {https://europepmc.org/article/MED/42968483},
note = {CC BY},
}
RIS
TY - JOUR
TI - Myeloid-Derived Growth Factor Alleviates Diabetic Non-Alcoholic Fatty Liver Disease by Up-Regulating ABCA1 and ABCG1 Expression via the AMPK/PPARγ/LXRα Pathway.
AU - Zeyu Chen
AU - Biying Meng
AU - Bingyi Wang
AU - Yan Ding
PY - 2026
DA - 2026/11/01
JO - Journal of cellular and molecular medicine
DO - 10.1111/jcmm.71428
UR - https://europepmc.org/article/MED/42968483
AB - The regulatory role of bone marrow in systemic metabolic processes remains incompletely characterized. Myeloid-derived growth factor (MYDGF) is a myeloid cell-secreted factor with emerging metabolic functions, but its action in diabetes-associated non-alcoholic fatty liver disease (DM NAFLD) is undefined. To investigate the influence of myeloid cell-derived MYDGF on DM NAFLD, both loss- and gain-of-function approaches were applied in vivo. DM NAFLD models were established in Mydgf-knockout (KO) mice, PpargΔLyz2 mice and PpargΔLyz2/KO (DKO) mice. For in vitro studies, primary Kupffer cells (KCs) were stimulated with high glucose and recombinant MYDGF (rMYDGF) and bone marrow cells (BMCs) were co-cultured with KCs via a transwell system. Protein levels related to DM NAFLD pathology and signalling pathways were quantified. In this study, we found that MYDGF was significantly downregulated in DM NAFLD mouse liver. Myeloid MYDGF deficiency exacerbated hepatic inflammation, lipogenesis, steatosis and macrophage infiltration, while reconstituting myeloid MYDGF reversed these phenotypes. rMYDGF attenuated inflammation, reduced macrophage foaming, decreased cholesterol content and increased efferocytosis. Mechanistically, MYDGF induced AMP-activated protein kinase (AMPK) phosphorylation, which subsequently activated the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) pathway in KCs and upregulated downstream ABCA1 and ABCG1 expression. These results identify the AMPK/PPARγ/LXRα-ABCA1/ABCG1 cascade as the core signalling axis mediating MYDGF's metabolic regulatory effects, which bridges the previously unrecognized functional linkage between myeloid cell function and hepatic lipid homeostasis, and explains the protective phenotype observed in MYDGF-reconstituted DM NAFLD mice. In conclusion, myeloid cell-derived MYDGF ameliorates DM NAFLD, decreases cholesterol content in macrophages and reduces lipid accumulation via the AMPK/PPARγ/LXRα pathway. MYDGF serves as a key mediator for bone marrow-liver metabolic crosstalk, indicating that the bone marrow may act as a potential endocrine target for the prevention and treatment of diabetes-related metabolic disorders.
SN - 1582-1838
SN - 1582-4934
ER -