Proteomic changes in the hypothalamus and retroperitoneal fat from male F344 rats subjected to repeated light-dark shifts.

Chronic circadian desynchronization induced by repeated 12 h light-dark cycle shifts conducted twice weekly resulted in elevated food intake, body weight gain, and retroperitoneal fat mass in male F344 rats. Using a proteomic approach, we found that repeated light-dark shifts caused changes in expression levels of five hypothalamic (four upregulated) and 22 retroperitoneal fat (13 upregulated) 2-DE protein spots. Proteins involved in carbohydrate metabolism and in the citric acid cycle were upregulated, indicating a positive energy balance status. In addition, the hypothalamic gamma-amino butyric acid (GABA) aminotransferase was upregulated, thus suggesting a connection between the brain GABAeric system and the modulation of food intake. Furthermore, the upregulation of fatty acid-binding protein 4 and the downregulation of 78 kDa glucose-regulated protein in the fat implicated the development of insulin resistance. We observed the upregulation of two antioxidant enzymes that might serve as protection against insulin dysfunction associated with oxidative stress. Finally, the downregulation of hypothalamic voltage-dependent anion-selective channel protein 1 and fat ATP synthase suggested a reduction in synthesis of mitochondrial ATP. These findings are in partial agreement with those of studies of obesity induced by genotype and a high-fat diet.