Background: The impairment in the insulin pathway that is called insulin resistance (IR), contributes to the imbalance in the glucose homeostasis. In the liver, this condition can
increase the activity of enzymes involved in the hepatic glucose production. Among these enzymes, piruvate carboxylase (PCB) has been shown great importance because of its role in the conversion of
pyruvate in oxaloacetate. Moreover, the increase in lipolysis in white adipose tissue (WAT) because of insulin resistance can increase the levels of free fatty acids (FFA) in the bloodstream and
contribute to the increment of Acetyl-CoA and PCB activity in the liver. On the other hand, the physical exercise has shown to be a great strategy against obesity and insulin resistance. In this line
of thought, several studies have been shown that the physical exercise reduces the hepatic glucose production. However, little is known about the regulation of these mechanisms. Therefore, studies
that evaluate the effects of physical exercise on PCB levels can elucidate new mechanisms by which exercise can regulate the hepatic glucose production. In the present study, we evaluated the role of
chronic physical exercise on the levels of PCB in hepatic tissue of obese and insulin resistant mice.
Methods: Swiss mice (4 weeks old) were divided into 3 groups: Sedentary Control (C) sedentary animals fed with control diet, Sedentary Obese (SO) sedentary animals fed with HFD and
Trained Obese (TO) animals fed with HFD and submitted to the training protocol. Protocol training was carried out for 1h/ day, 5 days/week, during 8 weeks and it was performed at the intensity of 60%
of maximum power, which was determined at the beginning of the experiment. During the last experimental week the insulin tolerance test (ITT) and glucose tolerance test (GTT) were performed. Twenty
four hours after the last physical exercise session the animals were euthanized and the liver was harvested for subsequent analysis.
Results: The mice subjected to chronic physical exercise showed decreased in body weight compared with SO group. Moreover, the physical exercise was able to increase the insulin
sensitivity compared with sedentary obese group. After this, we evaluated the phosphorylation and levels of Akt and PCB in the liver from the different groups. TO group showed increase in the
phosphorylation of Akt compared with SO group. Furthermore, SO showed increased levels of PCB compared with control group. Nevertheless, the physical exercise was able to decrease the levels of PCB
when the group TO was compared with SO.
Conclusions: Taking all results together, the physical exercise reduced body weight and increased insulin sensitivity as expected. These results can be explained due to the changes in
PCB levels in relation with SO group. Therefore, the mice fed with high fat diet showed increase in PCB levels. However, trained obese mice presented a significant decrease in levels of PCB, thus
physical exercise seems to be able to regulate hepatic gluconeogenesis through PCB protein.