Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats

Abstract

Obesity-induced endoplasmatic reticulum (ER) stress has been demonstrated to underlie the induction of obesity-induced JNK and NF-κB activation inflammatory responses, and generation of peripheral insulin resistance. On the other hand, exercise has been used as a crucial tool in obese and diabetic patients, and may reduce inflammatory pathway stimulation. However, the ability of exercise training to reverse endoplasmatic reticulum stress in adipose and hepatic tissue in obesity has not been investigated in the literature. Here, we demonstrate that exercise training ameliorates ER stress and insulin resistance in DIO-induced rats. Rats were fed with standard rodent chow (3,948 kcal kg(-1)) or high-fat diet (5,358 kcal kg(-1)) for 2 months. After that rats were submitted to swimming training (1 h per day, 5 days for week with 5% overload of the body weight for 8 weeks). Samples from epididymal fat and liver were obtained and western blot analysis was performed. Our results showed that swimming protocol reduces pro-inflammatory molecules (JNK, IκB and NF-κB) in adipose and hepatic tissues. In addition, exercise leads to reduction in ER stress, by reducing PERK and eIF2α phosphorylation in these tissues. In parallel, an increase in insulin pathway signaling was observed, as confirmed by increases in IR, IRSs and Akt phosphorylation following exercise training in DIO rats. Thus, results suggest that exercise can reduce ER stress, improving insulin resistance in adipose and hepatic tissue.

Hypothalamic endoplasmic reticulum stress of overtrained mice after recovery

“…1 demonstrated that animals receiving high-fat diet and submitted to swimming training reduced both inflammatory proteins (i.e., JNK, IkB, NF-kB) and ER stress (i.e., PERK phosphorylation and elF2alpha) in adipose and hepatic tissues 1 …”

“…However, some disturbances that culminate in increased immature protein synthesis, which produces unfolded and misfolded proteins, may lead to an adaptive response known as the unfolded protein response (UPR) 1,2 . An imbalance between the load and the ability to fold proteins is defined as the ER stress, occurring physiological changes in UPR signaling.…”

“…These proteins are connected to a chaperone binding protein (BiP) in the intraluminal domain remaining inactive. However, stress situations, including excessive immature proteins, recruit chaperones that reduce their association with the membrane proteins, allowing the autophosphorylation of IRE-1 and PERK and the cleavage of ATF-6 [1][2][3] . IRE-1 can form a ternary complex, IRE1-TRAF2-ASK1, because it connects with the adaptor protein tumor necrosis factor receptor-associated factor 2 (TRAF2) to activate apoptosis signal regulating kinase 1 (ASK1).…”

Fructose Consumption in the Development of Obesity and the Effects of Different Protocols of Physical Exercise on the Hepatic Metabolism

“…In addition, even though there was no reduction in body weight and adipose tissue, mRNA levels of pro-opiomelanocortin (POMC) were Once enhanced insulin activity in several tissues that are responsible for the metabolic control, the serum levels of pro-inflammatory proteins [65,67], and fasting glucose [61,72] are reduced. After 8 weeks of endurance training, da Luz et al…”

“…The same study also found decreased levels of proteins involved in gluconeogenesis, such as PEPCK and glucose-6-phosphatase (G6Pase). Aerobic exercise also proved to be able to reduce the phosphorylation of proteins kinase RNA-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2-α (eIF2α) [65], which are regarded as the greatest stress markers of endoplasmic reticulum [69]. Thus, the phosphorylation of insulin receptor tyrosine and their substrates and activation of protein kinase B (Akt) increased as well as decreased inflammation in this tissue.…”