Effects of short-term physical training on the interleukin-15 signalling pathway and glucose tolerance in aged rats.

PURPOSE: Interleukin-15 (IL-15) is a myokine that has been proposed to modulate skeletal muscle and adipose tissue mass, as well as insulin sensitivity. However, the evidence suggesting a role for IL-15 in improving whole-body insulin sensitivity and decreasing adiposity comes mainly from studies using supraphysiological levels of this cytokine. This study examined the effect of a short-term exercise training protocol on the protein content of IL-15, it's signaling pathway, and glucose tolerance in aged rats. METHODS: Fourteen Wistar rats were divided into Young Sedentary (Young, n = 4); Old Sedentary (Old, n = 5); Old Exercise (Old.Exe, n = 5) groups. The animals from the exercised group were submitted to a short-term physical exercise protocol for five days. At the end of physical training and after 16 h of the last exercise session, the animals were euthanized, and tissue collection was done. RESULTS: Physical exercise decreased epididymal and mesenteric fat mass and promoted positive effects on glucose tolerance and insulin sensitivity. Muscle IL-15 protein levels were not changed following the short-term physical exercise training with no alterations in the post-exercise IL-15-JAK/STAT signaling pathway. We found a tendency to increased HIF1α and a significant increase in its regulator, PHD2, in the skeletal muscle after exercise. CONCLUSION: The elderly rats submitted to short-term aerobic physical training did not present skeletal muscle alteration in the protein content of the IL-15 and IL-15-JAK/STAT signaling pathway. However, short-term aerobic physical training was able to modulate the expression of HIF1α and its regulator PHD2, suggesting an essential role of these proteins in improving post-exercise glucose tolerance and insulin sensitivity in elderly rats.

Aging is associated with increased TRB3, ER stress, and hepatic glucose production in the liver of rats.

TRB3, a mammalian homolog of Drosophila tribbles, plays an important role in multiple tissues and it has been implicated in stress response regulation and metabolic control. However, the role of hepatic TRB3 and its relationship with endoplasmic reticulum stress (ER stress) during aging has not been elucidated. Thus, the present study aimed to explore the association of aging with TRB3 and ER stress on the hepatic glucose production in Wistar rats. We found the TRB3 protein content to be higher in livers of old rats (27 months) compared to young (3 months) and middle-aged (17 months) rats. The increased content of hepatic TRB3 of the old rats was associated with insulin resistance (decreased protein kinase B (Akt) and Forkhead Box O1 (FoxO1) phosphorylation) and increased enzymes of gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase)). Moreover, aging was associated with activation of the endoplasmic reticulum stress pathway-related molecules, with an increase in phosphorylation of Inositol-requiring enzyme 1 (p-IRE1α), the protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), eukaryotic translation initiation factor-α (p-eIF2α), binding immunoglobulin protein (BiP), and the C/EBP homologous protein (CHOP) contents in rats. These molecular changes resulted in increased liver glucose production in response to the pyruvate challenge and hyperglycemia of the old rats. In conclusion, our results suggested that, by interfering with insulin signaling in the liver, TRB3 was associated with ER stress and increased hepatic glucose production in aging rats.