Profile of proteins involved in iron homeostasis and energy metabolism in multiple organs of leptin-deficient mice

Obesity is a global health problem. Its impacts are even more alarming when consider associated comorbidities, which include iron deficiency. Despite the importance of iron in metabolic function, the relationship between iron deficiency and metabolic dysregulation in obesity has not been fully addressed. Here, we evaluated the proteins involved in iron homeostasis and metabolism in multiple organs of leptin-deficient obese mice, a model that allows investigation of the progression of obesity. In the liver, proteins involved in glycaemia control were altered in both 3- and 5-month-old ob/ob mice (3mOB and 5mOB), but intracellular iron storage was reduced only in 3mOB. In the serum samples, glucose and cholesterol were increased in both 3mOB and 5mOB, with no alterations in iron markers. The pattern of liver proteins and serum metabolites indicate insulin-resistance state and glycemia dysregulation. In adipose tissue, 3mOB showed increased citrate synthase levels, while 5mOB showed increased MTCO2 and reduced ATP synthase levels. Ferritin was increased only in 5mOB. In the hippocampus, one of the most affected brain regions in obesity, increased MTCO2 and reduced ATP synthase levels were observed in 3mOB, while in 5mOB, increased OXCT1, a key enzyme for ketone body utilization, was observed. Reduction of ferritin levels was observed only in 5mOB. Thus, at 5 months, when the animals develop severe obesity, iron accumulates in adipose tissue but shows a reduction in the hippocampus. Our findings suggest that iron homeostasis is disrupted in a tissue-specific manner, with altered protein profiles that indicate metabolic dysregulation in multiple organs.