Physical exercise elicits UPR in the skeletal muscle: The role of c-Jun N-terminal kinase.

Objective: The mitochondrial unfolded protein response (UPR) is an adaptive cellular response to stress to ensure mitochondrial proteostasis and function. Here we explore the capacity of physical exercise to induce UPR in the skeletal muscle.

Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinformatics analyses.

Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4 mice.

Objective: Intriguingly, hyperinsulinemia, and hyperglycemia can predispose insulin resistance, obesity, and type 2 diabetes, leading to metabolic disturbances. Conversely, physical exercise stimulates skeletal muscle glucose uptake, improving whole-body glucose homeostasis. Therefore, we investigated the impact of short-term physical activity in a mouse model (Slc2a4) that spontaneously develops hyperinsulinemia and hyperglycemia even when fed on a chow diet.

Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise.

Dysfunction of the adipose tissue metabolism is considered as a significant hallmark of aging. It has been proposed that α-β hydrolase domain containing 5 (ABHD5) plays a critical role in the control of lipolysis. However, the role of ABHD5 in the control of lipolysis during aging or exercise is unknown.

Exercise alters the mitochondrial proteostasis and induces the mitonuclear imbalance and UPR in the hypothalamus of mice.

The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the mitonuclear imbalance and mitochondrial unfolded protein response (UPR) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPR in hypothalamic cells are unclear.

High-intensity exercise training induces mitonuclear imbalance and activates the mitochondrial unfolded protein response in the skeletal muscle of aged mice.

The impairment of mitochondrial metabolism is a hallmark of aging. Mitonuclear imbalance and the mitochondrial unfolded protein response (UPRmt) are two conserved mitochondrial mechanisms that play critical roles in ensuring mitochondrial proteostasis and function. Here, we combined bioinformatics, physiological, and molecular analyses to examine the role of mitonuclear imbalance and UPRmt in the skeletal muscle of aged rodents and humans.

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.

Aerobic Exercise Training Induces the Mitonuclear Imbalance and UPRmt in the Skeletal Muscle of Aged Mice.

The impairment of the mitochondrial functions is a hallmark of aging. During aging, there is a downregulation of two mechanisms strictly associated with mitochondrial integrity, including the mitonuclear imbalance (eg, imbalance in mitochondrial- versus nuclear-encoded mitochondrial proteins) and the mitochondrial unfolded protein response (UPRmt). Here, we evaluated the effects of aerobic exercise in the mitonuclear imbalance and UPRmt markers in the skeletal muscle of old mice.

NAD precursor increases aerobic performance in mice.

Purpose: Nicotinamide riboside (NR) acts as a potent NAD precursor and improves mitochondrial oxidative capacity and mitochondrial biogenesis in several organisms. However, the effects of NR supplementation on aerobic performance remain unclear. Here, we evaluated the effects of NR supplementation on the muscle metabolism and aerobic capacity of sedentary and trained mice.

Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice.

Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. The APPL1 mediates a positive effect on the insulin signaling through the interaction with the phosphoinositide 3-kinase (PI3K).

Nicotinamide riboside induces a thermogenic response in lean mice.

Aims: Nicotinamide Riboside (NR) is a NAD booster with wide physiological repercussion including the improvement on glucose and lipid homeostasis, increasing the life expectancy in mammals. However, the effects of NR on metabolism are only partially known. Here, we evaluated the effects of NR on the thermogenic response, highlighting the brown adipose tissue (BAT) in lean mice.

The role of physical exercise on Sestrin1 and 2 accumulations in the skeletal muscle of mice.

Aims: Sestrins, a class of stress-related proteins, is involved in the control of aging-induced organic dysfunctions and metabolic control. However, the factors that modulate the levels of Sestrins are poorly studied. Here, we evaluated the effects of acute and chronic aerobic exercise on Sestrin 1 (Sesn1) and Sesn2 protein contents in the skeletal muscle of mice.

Exercise increases Rho-kinase activity and insulin signaling in skeletal muscle.

The effects of physical exercise on insulin signaling and glycemic homeostasis are not yet fully understood. Recent findings elucidated the positive role of Rho-kinase (Rock) in increasing the glucose uptake through insulin receptor substrate-1 (IRS1) phosphorylation in the skeletal muscle. Here, we explored the effects of short-term exercise on Rock activity and insulin signaling.

Obesity Increases Mitogen-Activated Protein Kinase Phosphatase-3 Levels in the Hypothalamus of Mice.

Mitogen-activated Protein Kinase Phosphatase 3 (MKP-3) has been involved in the negative regulation of insulin signaling. The absence of MKP-3 is also associated with reduced adiposity, increased energy expenditure and improved insulin sensitivity. The MKP-3 is known as the main Erk1/2 phosphatase and FoxO1 activator, which has repercussions on the gluconeogenesis pathway and hyperglycemia in obese mice.

Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice.

Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot.

Physical exercise reduces pyruvate carboxylase (PCB) and contributes to hyperglycemia reduction in obese mice.

The present study evaluated the effects of exercise training on pyruvate carboxylase protein (PCB) levels in hepatic tissue and glucose homeostasis control in obese mice. Swiss mice were distributed into three groups: control mice (CTL), fed a standard rodent chow; diet-induced obesity (DIO), fed an obesity-inducing diet; and a third group, which also received an obesity-inducing diet, but was subjected to an exercise training protocol (DIO + EXE). Protocol training was carried out for 1 h/d, 5 d/wk, for 8 weeks, performed at an intensity of 60% of exhaustion velocity.