Aerobic exercise regulates blood lipid and insulin resistance via the toll‑like receptor 4‑mediated extracellular signal‑regulated kinases/AMP‑activated protein kinases signaling pathway

Abstract

Diabetes mellitus is a complicated metabolic disease with symptoms of hyperglycemia, insulin resistance, chronic damage and dysfunction of tissues, and metabolic syndrome for insufficient insulin production. Evidence has indicated that exercise treatments are essential in the progression of type‑ІІ diabetes mellitus, and affect insulin resistance and activity of islet β‑cells. In the present study, the efficacy and signaling mechanism of aerobic exercise on blood lipids and insulin resistance were investigated in the progression of type‑ІІ diabetes mellitus. Body weight, glucose metabolism and insulin serum levels were investigated in mouse models of type‑ІІ diabetes mellitus following experienced aerobic exercise. Expression levels of inflammatory factors, interleukin (IL)‑6, high‑sensitivity C‑reactive protein, tumor necrosis factor‑α and leucocyte differentiation antigens, soluble CD40 ligand in the serum were analyzed in the experimental mice. In addition, expression levels of toll‑like receptor 4 (TLR‑4) were analyzed in the liver cells of experimental mice. Changes of oxidative stress indicators, including reactive oxygen species, superoxide dismutase, glutathione and catalase were examined in the liver cells of experimental mice treated by aerobic exercise. Expression levels and activity of extracellular signal‑regulated kinases (ERK) and AMP‑activated protein kinase (AMPK) signaling pathways were investigated in the liver cells of mouse models of type‑ІІ diabetes mellitus after undergoing aerobic exercise. Aerobic exercise decreased the expression levels of inflammatory factors in the serum of mouse models of type‑ІІ diabetes mellitus. The results indicated that aerobic exercise downregulated oxidative stress indicators in liver cells from mouse models of type‑ІІ diabetes mellitus. In addition, the ERK and AMPK signaling pathways were inactivated by aerobic exercise in liver cells in mouse models of type‑ІІ diabetes mellitus. The activity of ERK and AMPK, and the function of islet β‑cells were observed to be improved in experimental mice treated with aerobic exercise. Furthermore, blood lipid metabolism and insulin resistance were improved by treatment with aerobic exercise. Body weight and glucose concentration of serology was markedly improved in mouse models of type‑ІІ diabetes mellitus. Furthermore, TLR‑4 inhibition markedly promoted ERK and AMPK expression levels and activity. Thus, these results indicate that aerobic exercise may improve blood lipid metabolism, insulin resistance and glucose plasma concentration in mouse models of type‑ІІ diabetes mellitus. Thus indicating aerobic exercise is beneficial for improvement of blood lipid and insulin resistance via the TLR‑4‑mediated ERK/AMPK signaling pathway in the progression of type‑ІІ diabetes mellitus.

Hyperlipidic Diet-induced Obesity Increased Proliferative Signals- AR, ERK1/2- on Mice Prostate, Which can be Restored through Physical Training

“…We also showed that physical exercise is able to reverse the increased cellular proliferation in the prostate after hyperlipidic diet through AR and ERK signaling pathways. Wang et al recently demonstrated that aerobic exercise increases the expression of ERK and AMPK in mice liver, corroborating to our data [32]. Thus, our results indicate that obesity and its metabolic disorders can trigger cell proliferation in the prostate through ERK activation, even in situations of androgen deficiency, and physical exercise may reverse this effect.…”

Exercise for Prevention and Relief of Cardiovascular Disease: Prognoses, Mechanisms, and Approaches

“…By improving the antioxidant enzymes and redox status in many organs and pathologies, the chronic treadmill exercise has an anti-inflammatory effect. Exercise alleviates oxidative stress through inactivating ERK/AMPK signaling pathway and decreases expression of inflammatory factors like IL-6, high-sensitivity CRP, TNF α , and leucocyte differentiation antigens in diabetes [96]. In renovascular hypertensive rats, ROS released by vascular endothelial cells impairs EDR by decreasing NO production and facilitating vasoconstriction.…”

The role of glucose homeostasis on immune function in response to exercise: The impact of low or higher energetic conditions

“…Mechanistic studies revealed a link between reduced expression of intracellular TLR pathways (JNK, IκB, andNF-κB) in adipose and hepatic tissue in conjunction with increased IR density and AKT phosphorylation (da Luz et al, 2011;Wang, Li, Wang, Zou, & Zhang, 2018). Moreover, exercise increases the expression of gene markers (AMAC1and IL-4) related to M2 through upregulation of transcription factors PGC-1α and PGC-1β (Yakeu et al, 2010).…”