Dysregulation of Zinc and Iron Balance in Adipose Tissue from Diabetic Sand Rats (Psammomys obesus)

Background: In obesity, the distribution and metabolic function of adipose tissue are of vast importance for the risk of type 2 diabetes development. The homeostasis of zinc and iron is believed to be disturbed in diabetic patients. Zinc dyshomeostasis could affect the metabolic function of adipose tissue as zinc is known to facilitate the functions of insulin within adipose tissue as well as take part in cell proliferation and apoptosis. Further, altered iron levels have been shown to affect insulin sensitivity. This study investigates the intracellular zinc regulation and total zinc and iron status in adipose tissues in obesity-linked, type 2 diabetes in the Psammomys obesus model. Methods: Subcutaneous and visceral adipose tissue were collected from diabetic (n=6) and non-diabetic animals (n=6). Total zinc and iron levels were analyzed by induced-coupled plasma mass spectrometry. Gene expressions of zinc transporters of the SLC30A and SLC39A family, regulating the intracellular zinc distribution, as well as several metabolic markers were investigated by RealTime-PCR. Results: Diabetic animals exhibited signs of an altered zinc homeostasis i. e. a re-distribution of total zinc within visceral adipose tissues and altered transcription of zinc regulatory proteins ZIP6, ZIP8, ZIP9, and ZnT9. Further, diabetic animals displayed an iron accumulation in visceral adipose tissue that was positively correlated with insulin degrading enzyme and peroxisome proliferator-activated receptor gamma. Conclusion: Psammomys obesus, a complex animal model of diet-induced type 2 diabetes, exhibits changes in the mineral status of zinc and iron in visceral adipose tissue. These changes might be related to the altered insulin sensitivity and metabolic function of visceral adipose tissue seen in type 2 diabetes. This study warrants further investigations into the role minerals, especially zinc and iron, play in the pathophysiology of type 2 diabetes.