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

Abd Al Roof Higazi, Emad Maraga, Saja Baraghithy, Shiran Udi, Shahar Azar, Ann Saada, Benjamin Glaser, Dana Avrahami, Suhair Abdeen, Zenab Hamdan, Joseph Tam, Rami Abu Fanne*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageAmerican English
Article number108802
JournaliScience
Volume27
Issue number2
DOIs
StatePublished - 16 Feb 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Keywords

  • Cell biology
  • Endocrinology
  • Molecular physiology

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