Leptin Receptor-Deficient db/db Mice Show Significant Heterogeneity in Response to High Non-heme Iron Diet

Sabine Paeschke; Karsten Winter; Ingo Bechmann; Nora Klöting; Matthias Blüher; Petra Baum; Joanna Kosacka; Marcin Nowicki

doi:10.3389/fnut.2021.741249

Leptin Receptor-Deficient db/db Mice Show Significant Heterogeneity in Response to High Non-heme Iron Diet

Front Nutr. 2021 Sep 27:8:741249. doi: 10.3389/fnut.2021.741249. eCollection 2021.

Authors

Sabine Paeschke¹, Karsten Winter¹, Ingo Bechmann¹, Nora Klöting², Matthias Blüher^{2

3}, Petra Baum⁴, Joanna Kosacka^{3

5}, Marcin Nowicki¹

Affiliations

¹ Institute of Anatomy, University of Leipzig, Leipzig, Germany.
² Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen at the University of Leipzig, Leipzig, Germany.
³ Department of Medicine, University of Leipzig, Leipzig, Germany.
⁴ Department of Neurology, University of Leipzig, Leipzig, Germany.
⁵ Applied Molecular Hepatology Lab, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Leipzig, Germany.

Abstract

Recent studies have shown an association between iron homeostasis, obesity and diabetes. In this work, we investigated the differences in the metabolic status and inflammation in liver, pancreas and visceral adipose tissue of leptin receptor-deficient db/db mice dependent on high iron concentration diet. 3-month-old male BKS-Leprdb/db/JOrlRj (db/db) mice were divided into two groups, which were fed with different diets containing high iron (29 g/kg, n = 57) or standard iron (0.178 g/kg; n = 42) concentrations for 4 months. As anticipated, standard iron-fed db/db mice developed obesity and diabetes. However, high iron-fed mice exhibited a wide heterogeneity. By dividing into two subgroups at the diabetes level, non-diabetic subgroup 1 (<13.5 mmol/l, n = 30) significantly differed from diabetic subgroup two (>13.5 mmol/l, n = 27). Blood glucose concentration, HbA1c value, inflammation markers interleukin six and tumor necrosis factor α and heme oxygenase one in visceral adipose tissue were reduced in subgroup one compared to subgroup two. In contrast, body weight, C-peptide, serum insulin and serum iron concentrations, pancreatic islet and signal ratio as well as cholesterol, LDL and HDL levels were enhanced in subgroup one. While these significant differences require further studies and explanation, our results might also explain the often-contradictory results of the metabolic studies with db/db mice.

Keywords: db/db mice; diabetes mellitus; inflammation; iron; metabolism; obesity.