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Publication : Characterization of metabolic alterations in the lean metabolically unhealthy alpha defensin transgenic mice.

First Author  Higazi AA Year  2024
Journal  iScience Volume  27
Issue  2 Pages  108802
PubMed ID  38318380 Mgi Jnum  J:351221
Mgi Id  MGI:7581636 Doi  10.1016/j.isci.2024.108802
Citation  Higazi AA, et al. (2024) Characterization of metabolic alterations in the lean metabolically unhealthy alpha defensin transgenic mice. iScience 27(2):108802
abstractText  Inflammation is consistently linked to dysmetabolism. In transgenic mice (Def(+/+)) model the neutrophilic peptide, alpha defensin, proved atherogenic. This phenotype occurred despite favorable cholesterol and glucose levels, and lower body weight and blood pressure. In this study, integration of metabolic&behavioral phenotyping system, endocrine, biochemical and mitochondrial assessment, pathological and immunohistochemical tests, and multiple challenge tests was established to explore the metabolic impact of alpha defensin. Compared to the control group, Def(+/+) mice exhibited lower total energy expenditure and carbohydrate utilization, and higher fat oxidation. Their ACTH-cortisol and thyroid profiles were intact. Intriguingly, they had low levels of glucagon, with high ammonia, uric acid, triglyceride, and lactate. Mitochondrial evaluations were normal. Overall, defensin-induced hypoglucagonemia is associated with lipolysis, restricted glucose oxidation, and enhanced wasting. Def(+/+) mice may be a useful model for studying the category of lean, apparently metabolically healthy, and atherosclerotic phenotype, with insight into a potential inflammatory-metabolic link.
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