BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway.
<h4>Purpose</h4>This study mimics the metabolic environment of metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetic mellitus (DM) to investigate the function of BRCA1 in regulating glucose and lipid metabolism in hepatocytes under high glucose (HG) settings.<h...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0318696 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849738086058033152 |
|---|---|
| author | Cui Ma Xiaodi Yang Liyin Zhang Jie Zhang Youyou Zhang Xiaofeng Hu |
| author_facet | Cui Ma Xiaodi Yang Liyin Zhang Jie Zhang Youyou Zhang Xiaofeng Hu |
| author_sort | Cui Ma |
| collection | DOAJ |
| description | <h4>Purpose</h4>This study mimics the metabolic environment of metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetic mellitus (DM) to investigate the function of BRCA1 in regulating glucose and lipid metabolism in hepatocytes under high glucose (HG) settings.<h4>Methods</h4>MASLD and DM-related datasets (GSE89632, GSE95849) were screened for overlapping genes, Protein-Protein Interaction (PPI) network and enrichment analyses were performed. Then, quantitative real-time polymerase chain reaction (qRT-PCR), Western Blotting (WB), and enzymatic colorimetric assays to examine the expression changes of BRCA1 in mouse primary hepatocytes under HG conditions and the impact of the combined PI3K/Akt signaling pathway on key metabolic markers of gluconeogenesis and lipid metabolism.<h4>Results</h4>Our study identified seven key overlapping genes (AURKA, BRCA1, ISG15, NUSAP1, OAS1, RSAD2, TLR7) between MASLD and DM. Experiments found that when BRCA1 was overexpressed in mouse primary hepatocytes, intracellular triglyceride content and lipid metabolism-related biomarkers (such as PEPCK, SREBP-1c, G6Pase, and FAS) were significantly increased in HG circumstances. However, the knockdown of BRCA1 reduced the expression of these indicators. Besides, we also observed that under HG conditions, the expression of proteins linked to the PI3K/Akt signaling pathway was negatively regulated by BRCA1 expression. Moreover, TG content and expression of lipid metabolism markers are also regulated by BRCA1 and PI3K/Akt pathway inhibitor Ly294002.<h4>Conclusion</h4>As a key regulator of hepatocyte metabolism under HG conditions, BRCA1 can participate in regulating glucose and lipid metabolism in mouse primary hepatocytes through the PI3K/AKT signaling pathway, which be able to become a possible remedy strategy for DM with MASLD. |
| format | Article |
| id | doaj-art-6baadcb6d7724602962d2dd4c190776d |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-6baadcb6d7724602962d2dd4c190776d2025-08-20T03:06:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01203e031869610.1371/journal.pone.0318696BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway.Cui MaXiaodi YangLiyin ZhangJie ZhangYouyou ZhangXiaofeng Hu<h4>Purpose</h4>This study mimics the metabolic environment of metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetic mellitus (DM) to investigate the function of BRCA1 in regulating glucose and lipid metabolism in hepatocytes under high glucose (HG) settings.<h4>Methods</h4>MASLD and DM-related datasets (GSE89632, GSE95849) were screened for overlapping genes, Protein-Protein Interaction (PPI) network and enrichment analyses were performed. Then, quantitative real-time polymerase chain reaction (qRT-PCR), Western Blotting (WB), and enzymatic colorimetric assays to examine the expression changes of BRCA1 in mouse primary hepatocytes under HG conditions and the impact of the combined PI3K/Akt signaling pathway on key metabolic markers of gluconeogenesis and lipid metabolism.<h4>Results</h4>Our study identified seven key overlapping genes (AURKA, BRCA1, ISG15, NUSAP1, OAS1, RSAD2, TLR7) between MASLD and DM. Experiments found that when BRCA1 was overexpressed in mouse primary hepatocytes, intracellular triglyceride content and lipid metabolism-related biomarkers (such as PEPCK, SREBP-1c, G6Pase, and FAS) were significantly increased in HG circumstances. However, the knockdown of BRCA1 reduced the expression of these indicators. Besides, we also observed that under HG conditions, the expression of proteins linked to the PI3K/Akt signaling pathway was negatively regulated by BRCA1 expression. Moreover, TG content and expression of lipid metabolism markers are also regulated by BRCA1 and PI3K/Akt pathway inhibitor Ly294002.<h4>Conclusion</h4>As a key regulator of hepatocyte metabolism under HG conditions, BRCA1 can participate in regulating glucose and lipid metabolism in mouse primary hepatocytes through the PI3K/AKT signaling pathway, which be able to become a possible remedy strategy for DM with MASLD.https://doi.org/10.1371/journal.pone.0318696 |
| spellingShingle | Cui Ma Xiaodi Yang Liyin Zhang Jie Zhang Youyou Zhang Xiaofeng Hu BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway. PLoS ONE |
| title | BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway. |
| title_full | BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway. |
| title_fullStr | BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway. |
| title_full_unstemmed | BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway. |
| title_short | BRCA1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction-associated steatotic liver disease via the PI3K/Akt signaling pathway. |
| title_sort | brca1 regulates glucose and lipid metabolism in diabetes mellitus with metabolic dysfunction associated steatotic liver disease via the pi3k akt signaling pathway |
| url | https://doi.org/10.1371/journal.pone.0318696 |
| work_keys_str_mv | AT cuima brca1regulatesglucoseandlipidmetabolismindiabetesmellituswithmetabolicdysfunctionassociatedsteatoticliverdiseaseviathepi3kaktsignalingpathway AT xiaodiyang brca1regulatesglucoseandlipidmetabolismindiabetesmellituswithmetabolicdysfunctionassociatedsteatoticliverdiseaseviathepi3kaktsignalingpathway AT liyinzhang brca1regulatesglucoseandlipidmetabolismindiabetesmellituswithmetabolicdysfunctionassociatedsteatoticliverdiseaseviathepi3kaktsignalingpathway AT jiezhang brca1regulatesglucoseandlipidmetabolismindiabetesmellituswithmetabolicdysfunctionassociatedsteatoticliverdiseaseviathepi3kaktsignalingpathway AT youyouzhang brca1regulatesglucoseandlipidmetabolismindiabetesmellituswithmetabolicdysfunctionassociatedsteatoticliverdiseaseviathepi3kaktsignalingpathway AT xiaofenghu brca1regulatesglucoseandlipidmetabolismindiabetesmellituswithmetabolicdysfunctionassociatedsteatoticliverdiseaseviathepi3kaktsignalingpathway |