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Dysregulated liver lipid metabolism and innate immunity associated with hepatic steatosis in neonatal BBdp rats and NOD mice.
- Source :
-
Scientific reports [Sci Rep] 2019 Oct 10; Vol. 9 (1), pp. 14594. Date of Electronic Publication: 2019 Oct 10. - Publication Year :
- 2019
-
Abstract
- In a previous study we reported that prediabetic rats have a unique gene signature that was apparent even in neonates. Several of the changes we observed, including enhanced expression of pro-inflammatory genes and dysregulated UPR and metabolism genes were first observed in the liver followed by the pancreas. In the present study we investigated further early changes in hepatic innate immunity and metabolism in two models of type 1 diabetes (T1D), the BBdp rat and NOD mouse. There was a striking increase in lipid deposits in liver, particularly in neonatal BBdp rats, with a less striking but significant increase in neonatal NOD mice in association with dysregulated expression of lipid metabolism genes. This was associated with a decreased number of extramedullary hematopoietic clusters as well as CD68 <superscript>+</superscript> macrophages in the liver of both models. In addition, PPARɣ and phosphorylated AMPKα protein were decreased in neonatal BBdp rats. BBdp rats displayed decreased expression of antimicrobial genes in neonates and decreased M2 genes at 30 days. This suggests hepatic steatosis could be a common early feature in development of T1D that impacts metabolic homeostasis and tolerogenic phenotype in the prediabetic liver.
- Subjects :
- Animals
Animals, Newborn
Antigens, CD metabolism
Antigens, Differentiation, Myelomonocytic metabolism
Diabetes Mellitus, Type 1 immunology
Diabetes Mellitus, Type 1 physiopathology
Disease Models, Animal
Female
Gene Expression Profiling
Liver metabolism
Liver physiopathology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Phenotype
Phosphorylation
Polymerase Chain Reaction
Rats
Triglycerides metabolism
Fatty Liver immunology
Fatty Liver physiopathology
Immunity, Innate
Lipid Metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31601915
- Full Text :
- https://doi.org/10.1038/s41598-019-51143-7