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
Affiliations
Abd Al-Roof Higazi
Department of Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem 9112001, Israel
Emad Maraga
Department of Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem 9112001, Israel
Saja Baraghithy
Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
Shiran Udi
Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
Shahar Azar
Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
Ann Saada
Department of Genetics, Hadassah Medical Center, Jerusalem, Isarel; Faculty of Medicine, Hebrew University, Jerusalem, Isarel; Department of Laboratory Sciences, Hadassah Academic College, Jerusalem, Isarel
Benjamin Glaser
Endocrinology and Metabolism Department, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Dana Avrahami
Department of Developmental Biology and Cancer Research, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
Suhair Abdeen
Department of Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem 9112001, Israel
Zenab Hamdan
Endocrinology and Metabolism Department, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Joseph Tam
Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
Rami Abu Fanne
Department of Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem 9112001, Israel; Department of Cardiology, Hillel Yaffe Medical Center, Hadera, Israel; Corresponding author
Summary: 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.
