ArticleAntioxidants (Basel, Switzerland)2023
Non-Esterified Fatty Acid-Induced Apoptosis in Bovine Granulosa Cells via ROS-Activated PI3K/AKT/FoxO1 Pathway.
Article in Antioxidants (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 25 citations in OpenAlex.
- Carboxypeptidase A6 contributes to bovine enterovirus F production through apoptosis-associated PI3K/AKT/FOXO1 signaling.Virulence · 2026Article
- Guanxinning Tablet Ameliorates Erectile Dysfunction in Diabetes Mellitus Rats with Involvement of PI3K/Akt/FOXO1 Signaling Pathway Modulation.Biomedicines · 2026Article
- Article
- GLS1 governs vascular smooth muscle cell phenotypic switching and aortic dissection via glutamate metabolism.JCI insight · 2026Article
- Dysregulated post‑translational modifications in granulosa cells drive ovarian dysfunction and potential infertility applications (Review).International journal of molecular medicine · 2026Review
- PDK4 is critical for metabolic regulation and progesterone production in bovine granulosa cells†.Biology of reproduction · 2026Article
- Immunometabolic-uterine-ovarian interactions and flushing therapy in dairy cows: a narrative review.Veterinary world · 2026Review
- Ginseng Peptide Improves the Cryopreservation Efficiency and Fertilization Potential of Yak Semen via FOXO1/PI3K/AKT Axis.Antioxidants (Basel, Switzerland) · 2026Article
- The Impact of Oxidative Stress Imbalance on Ovarian Function and Its Mechanisms.International journal of general medicine · 2026Review
- Article
- NEFA Promotes Bovine Granulosa Cell Apoptosis via Activation of the PERK/eIF2α/ATF4/CHOP Pathway.Veterinary sciences · 2025Article
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- Artificially fermented dark loose tea ameliorates metabolic-associated fatty liver disease by activating the PI3K/AKT signalling pathway and regulating gut microbiota dysbiosis.Food chemistry: X · 2025Article
- NDUFAB1 as a Novel Regulator of NEFA-Induced Metabolic Dysfunction in Bovine Adipocytes.Animals : an open access journal from MDPI · 2025Article
- Elevated Linoleic Acid Intake Becomes a Risk Factor for Polycystic Ovary Syndrome by Affecting Ovarian Granulosa Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Regulatory Effects of Zhenxin Formula in Treating Doxorubicin-Induced Heart Failure: Network Pharmacology and Animal Experimental Verification.Drug design, development and therapy · 2025Article
- The Phytochemical Profile of the Petroleum Ether Extract ofInternational journal of molecular sciences · 2024Article
- Elevated RBP4 in Subclinical Ketosis Cows Inhibits Follicular Granulosa Cell Proliferation and Steroid Hormone Synthesis.Animals : an open access journal from MDPI · 2024Article
- Comparative Metabolomic Profiling of L-Histidine and NEFA Treatments in Bovine Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Non-esterified fatty acid (NEFA), one of negative energy balance (NEB)'s most well-known products, has a significant impact on cows' reproductive potential. Our study used an in vitro model to investigate the deleterious effects of NEFA on bovine granulosa cells (BGCs) and its underlying molecular mechanism. The results showed that high levels of NEFA led to the accumulation of reactive oxygen species (ROS), increased the expression of apoptosis-related factors such as Bcl2-Associated X/B-cell lymphoma-2 (Bax/Bcl-2) and Caspase-3, and down-regulated steroid synthesis-related genes such as sterol regulatory element binding protein 1 (SREBP-1), cytochrome P450c17 (CYP17), and cytochrome P450 aromatase (CYP19), to promote oxidative stress, cell apoptosis, and steroid hormone synthesis disorders in BGCs. In addition, NEFA significantly inhibited phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT) activity and increased forkhead box O1 (FoxO1) expression. To further explore the role of the PI3K/AKT/FoxO1 signaling pathway in NEFA, we found that pretreatment with AKT-specific activator SC79 (5 mg/mL) for 2 h or transfection with FoxO1 knockdown siRNA in BGCs could alleviate the negative effects of NEFA treatment by decreasing Bax/Bcl-2 ratio and Caspase-3 expression, and upregulating SREBP-1, CYP17, and CYP19 expression. Meanwhile, SC79 significantly inhibited NEFA-induced dephosphorylation and massive nuclear translocation of FoxO1. Taken together, the NEFA induced oxidative stress, apoptosis, and steroid hormone synthesis disorders in BGCs by inhibiting the PI3K/AKT pathway that regulates FoxO1 phosphorylation and nuclear translocation. Our findings help to clarify the molecular mechanisms underlying the negative effects of high levels of NEFA on BGCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.