Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands
The liver plays a central role in fat storage, but little is known about physiological fat accumulation during early development. Here we investigated a transient surge in hepatic lipid droplets observed in newborn mice immediately after birth. We developed a novel model to quantify liver fat conten...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227525000045 |
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| author | Wanderson Ferreira da Silva Júnior Karen Marques de Oliveira Costa Hortência Maciel Castro Oliveira Maísa Mota Antunes Kassiana Mafra Brenda Naemi Nakagaki Pedro Sérgio Corradi da Silva Júlia Duarte Megale Sarah Campos de Sales Douglas Carvalho Caixeta Mário Machado Martins Robinson Sabino-Silva Cristina Maria Pinto de Paula Luiz Ricardo Goulart Rafael Machado Rezende Gustavo Batista Menezes |
| author_facet | Wanderson Ferreira da Silva Júnior Karen Marques de Oliveira Costa Hortência Maciel Castro Oliveira Maísa Mota Antunes Kassiana Mafra Brenda Naemi Nakagaki Pedro Sérgio Corradi da Silva Júlia Duarte Megale Sarah Campos de Sales Douglas Carvalho Caixeta Mário Machado Martins Robinson Sabino-Silva Cristina Maria Pinto de Paula Luiz Ricardo Goulart Rafael Machado Rezende Gustavo Batista Menezes |
| author_sort | Wanderson Ferreira da Silva Júnior |
| collection | DOAJ |
| description | The liver plays a central role in fat storage, but little is known about physiological fat accumulation during early development. Here we investigated a transient surge in hepatic lipid droplets observed in newborn mice immediately after birth. We developed a novel model to quantify liver fat content without tissue processing. Using high-resolution microscopy assessed the spatial distribution of lipid droplets within hepatocytes. Lugol's iodine staining determined the timing weaning period, and milk deprivation experiments investigated the relationship between milk intake and fat accumulation. Lipidomic analysis revealed changes in the metabolic profile of the developing liver. Finally, we investigated the role of Toll-like receptor 4 (TLR4) signaling in fat storage using knockout mice and cell-specific deletion strategies. Newborn mice displayed a dramatic accumulation of hepatic lipid droplets within the first 12 h after birth, persisting for the initial two weeks of life. This pattern coincided with exclusive milk feeding and completely abated by the third week, aligning with weaning. Importantly, the observed fat accumulation shared characteristics with established models of pathological steatosis, suggesting potential biological relevance. Lipid droplets were primarily localized within the cytoplasm of hepatocytes. Milk deprivation experiments demonstrated that milk intake is the primary driver of this transient fat accumulation. Lipidomic analysis revealed significant changes in the metabolic profile of newborn livers compared to adults. Interestingly, several highly abundant lipids in newborns were identified as putative ligands for TLR4. Subsequent studies using TLR4-deficient mice and cell-specific deletion revealed that TLR4 signaling, particularly within hepatocytes, plays a critical role in driving fat storage within the newborn liver. Additionally, a potential collaboration between metabolic and immune systems was suggested by the observed effects of myeloid cell-specific TLR4 ablation. This study demonstrates a unique phenomenon of transient hepatic fat accumulation in newborn mice driven by milk intake and potentially regulated by TLR4 signaling, particularly within hepatocytes. |
| format | Article |
| id | doaj-art-987d5d1a967e46edbfecf140360791da |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-987d5d1a967e46edbfecf140360791da2025-02-10T04:33:27ZengElsevierJournal of Lipid Research0022-22752025-02-01662100744Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligandsWanderson Ferreira da Silva Júnior0Karen Marques de Oliveira Costa1Hortência Maciel Castro Oliveira2Maísa Mota Antunes3Kassiana Mafra4Brenda Naemi Nakagaki5Pedro Sérgio Corradi da Silva6Júlia Duarte Megale7Sarah Campos de Sales8Douglas Carvalho Caixeta9Mário Machado Martins10Robinson Sabino-Silva11Cristina Maria Pinto de Paula12Luiz Ricardo Goulart13Rafael Machado Rezende14Gustavo Batista Menezes15Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilInnovation Center in Salivary Diagnostics and Nanobiotechnology, Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Minas Gerais, BrazilLaboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, BrazilInnovation Center in Salivary Diagnostics and Nanobiotechnology, Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Minas Gerais, BrazilCenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilLaboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, Minas Gerais, BrazilAnn Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACenter for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; For correspondence: Gustavo Batista MenezesThe liver plays a central role in fat storage, but little is known about physiological fat accumulation during early development. Here we investigated a transient surge in hepatic lipid droplets observed in newborn mice immediately after birth. We developed a novel model to quantify liver fat content without tissue processing. Using high-resolution microscopy assessed the spatial distribution of lipid droplets within hepatocytes. Lugol's iodine staining determined the timing weaning period, and milk deprivation experiments investigated the relationship between milk intake and fat accumulation. Lipidomic analysis revealed changes in the metabolic profile of the developing liver. Finally, we investigated the role of Toll-like receptor 4 (TLR4) signaling in fat storage using knockout mice and cell-specific deletion strategies. Newborn mice displayed a dramatic accumulation of hepatic lipid droplets within the first 12 h after birth, persisting for the initial two weeks of life. This pattern coincided with exclusive milk feeding and completely abated by the third week, aligning with weaning. Importantly, the observed fat accumulation shared characteristics with established models of pathological steatosis, suggesting potential biological relevance. Lipid droplets were primarily localized within the cytoplasm of hepatocytes. Milk deprivation experiments demonstrated that milk intake is the primary driver of this transient fat accumulation. Lipidomic analysis revealed significant changes in the metabolic profile of newborn livers compared to adults. Interestingly, several highly abundant lipids in newborns were identified as putative ligands for TLR4. Subsequent studies using TLR4-deficient mice and cell-specific deletion revealed that TLR4 signaling, particularly within hepatocytes, plays a critical role in driving fat storage within the newborn liver. Additionally, a potential collaboration between metabolic and immune systems was suggested by the observed effects of myeloid cell-specific TLR4 ablation. This study demonstrates a unique phenomenon of transient hepatic fat accumulation in newborn mice driven by milk intake and potentially regulated by TLR4 signaling, particularly within hepatocytes.http://www.sciencedirect.com/science/article/pii/S0022227525000045livernewbornlipid dropletsmilkTLR4palmitic acid |
| spellingShingle | Wanderson Ferreira da Silva Júnior Karen Marques de Oliveira Costa Hortência Maciel Castro Oliveira Maísa Mota Antunes Kassiana Mafra Brenda Naemi Nakagaki Pedro Sérgio Corradi da Silva Júlia Duarte Megale Sarah Campos de Sales Douglas Carvalho Caixeta Mário Machado Martins Robinson Sabino-Silva Cristina Maria Pinto de Paula Luiz Ricardo Goulart Rafael Machado Rezende Gustavo Batista Menezes Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands Journal of Lipid Research liver newborn lipid droplets milk TLR4 palmitic acid |
| title | Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands |
| title_full | Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands |
| title_fullStr | Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands |
| title_full_unstemmed | Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands |
| title_short | Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands |
| title_sort | physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by tlr4 ligands |
| topic | liver newborn lipid droplets milk TLR4 palmitic acid |
| url | http://www.sciencedirect.com/science/article/pii/S0022227525000045 |
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