[Role of NLRP3 inflammasome in diabetes mellitus and exercise intervention].

Chronic inflammatory reaction has been established as an important sign of the occurrence and development of diabetes mellitus (DM), accompanied by the production of a large number of inflammatory factors, thus aggravating the disease progression. As an important non-invasive intervention measure to inhibit inflammation, exercise plays a very important role in the amelioration of DM. NOD-like receptor protein 3 (NLRP3) inflammasome, a regulatory factor of inflammatory response, can induce a variety of inflammatory cascades and cell death, which are closely related to glucose uptake and dyslipidemia regulation. The development of DM can be postponed with exercise. Previous studies have reported the effects of NLRP3 inflammasome on DM, but the crucial role of exercise in this process remains unclear. Therefore, this paper reviews the research progress on the improving effects of exercise intervention on the symptoms of DM by mediating NLRP3 inflammasome, providing a novel theoretical foundation for understanding the prevention and treatment of DM through exercise.

[IL-27: a novel cytokine mediating immune related diseases].

Interleukin 27 (IL-27) is a pleiotropic cytokine that is involved in the regulation of the body's innate and adaptive immunity. Previous studies have shown that IL-27 mediates a variety of inflammatory responses in vivo. With the development of animal models and technical tools, several studies have shown that it is also closely associated with autoimmune diseases and other immune related diseases, and is considered as an important candidate for the treatment of viral disease, autoimmune diseases, tumors and obesity. Therefore, this paper reviews recent progress on the role of IL-27 in acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis, tumors and obesity, with the aim of providing new ideas for the treatment of immune related diseases.

[Effects of aerobic exercise and dietary intervention on testicular oxidative stress in obese mice].

OBJECTIVE: Through aerobic exercise and diet intervention on obese mice, the effects of exercise and diet intervention on testicular oxidative stress and p38MAPK-NF-κB pathway were investigated in obese mice. METHODS: Seventeen C57BL/6J mice were randomly divided into a normal diet group (ND), and 37 mice were divided into a high-fat diet group (HFD), the high-fat diet accounted for 40% of fat. After 12 weeks of feeding, 3 obesity-resistant mice were excluded from the HFD group, and the remaining 34 were successfully modeled. The mice in ND group were then divided into normal diet control group (NC, n=8) and normal diet and exercise group (NE, n=9). The mice in HFD group were divided into obese high-fat diet control group (OC, n=8), obese high-fat diet and exercise group (OE, n=9), obese normal diet group (ONC, n=8), and obese normal diet and exercise group (ONE, n=9). Each group continued to feed for 8 weeks, and the NE, OE and ONE groups performed treadmill exercise for 8 weeks at a speed of 20 m/min, 60 min/d, 6 d/week. Blood and testicular tissue samples were collected 36～40 h after the last exercise. Serum testosterone and testicular oxidative stress (MDA, T-SOD, T-AOC) levels were detected by ELISA, and testicular p38MAPK-NF-κB levels were detected by RT-PCR and Western blot. RESULTS: Compared with the NC group, the body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels in the OC group were increased significantly (P＜0.01), while the levels of testicular SOD, testis coefficient and blood testosterone were decreased significantly (P＜0.01); the body fat parameters of the mice in the NE group were decreased significantly (P＜0.05), and the serum level of testosterone was increased significantly (P＜0.01). Compared with the OC group, the body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels were decreased significantly in the OE group (P＜0.05 or 0.01), and the testicular SOD and blood testosterone levels were increased significantly (P＜0.01); Body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels were decreased significantly in ONC group (P＜0.01), while testicular SOD level and testis coefficient were increased significantly (P＜0.05); Body fat parameters, testicular MDA and testicular p38MAPK-NF-κB mRNA and protein levels of mice in ONE group were decreased significantly (P＜0.01), while testicular SOD, testis coefficient and blood testosterone levels were increased significantly (P＜0.01). CONCLUSION: Obesity induces oxidative stress in the testis of mice, up-regulates the level of p38MAPK-NF-κB, and reduces the level of blood testosterone; exercise, diet and exercise*diet interventions can reduce testicular oxidative stress and down-regulate testicular p38MAPK-NF-κB levels by reducing body fat.

[Effects of exercise intervention on mitochondrial-derived peptide MOTS-c in the germ cells of obese men].

Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a newly discovered mitochondrial-derived peptide with the main functions of promoting glucose metabolism and reducing adipose tissue. MOTS-c was found to be a substance that can mimic the motor effect and improve the motor ability. It is sex-related and the circulating MOTS-c level is decreased in obese males. Obesity can cause male reproductive dysfunction, while exercise can improve obesity-induced reduction of male reproductive function. This article discusses the effect of exercise intervention on the mitochondrial-derived peptide MOTS-c in the germ cells of obese men.

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1-SIRT1-PGC-1α.

AIMS/HYPOTHESIS: Adiponectin stimulates mitochondrial biogenesis through peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a major regulator of mitochondrial biogenesis. MOTS-c (mitochondrial open reading frame of the 12S rRNA) is a biologically active mitochondrial-derived peptide encoded by mitochondrial DNA. It influences the mechanisms of obesity and diabetes. We hypothesised that the adiponectin pathway may regulate the production and/or secretion of MOTS-c in skeletal muscle. We aimed to determine whether exercise and adiponectin affect MOTS-c to improve insulin resistance in mice. METHODS: To investigate this hypothesis, we used wild-type C57BL/6 mice subjected to high-fat diet, an exercise regimen, and i.p. injection of recombinant mouse adiponectin (Acrp30) or MOTS-c, and adiponectin knockout (Adipoq-/-) mice (C57BL/6 background) subjected to i.p. injection of Acrp30. C2C12 myotubes were also treated with sirtuin 1 (SIRT1) inhibitor, PGC-1α inhibitor, SIRT1 activator, plasmid-expressed active APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper), pcDNA-SIRT1, or siRNA against APPL1, SIRT1 or PGC-1α. RESULTS: In Adipoq-/- mice, MOTS-c levels in the plasma and skeletal muscle were downregulated. In C2C12 myotubes, adiponectin increased the mRNA expression of MOTS-c. APPL1 protein level following adiponectin treatment positively correlated with MOTS-c protein and mRNA levels in C2C12 myotubes. SIRT1 overexpression increased the adiponectin-induced mRNA and protein expression of MOTS-c, SIRT1 and PGC-1α. Pharmacologic and genetic inhibition of PGC-1α suppressed the increases in MOTS-c mRNA and protein levels induced by SIRT1 overexpression. In mice, plasma and skeletal muscle MOTS-c levels were significantly downregulated following high-fat-diet. Exercise and i.p. Acrp30 or MOTS-c increased MOTS-c levels and adiponectin mRNA and protein expression in the plasma and skeletal muscle. CONCLUSIONS/INTERPRETATION: Our findings showed that the APPL1-SIRT1-PGC-1α pathway regulates the production and/or secretion of skeletal muscle MOTS-c by mediating adiponectin signalling. Our study provides an insight into the cellular and molecular pathways underlying the pathogenesis of diabetes and shows that MOTS-c is a potential novel therapeutic target in the treatment of diabetes. Graphical abstract.

[Effects of acute and chronic exercise on fat PI3K/AKT/GLUT4 signal pathway in type 2 diabetic rats].

OBJECTIVE: To study the effects of acute and chronic exercise on phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)/glucose transporter 4(GLUT4)signaling pathway in adipose tissue of rats with type 2 diabetes mellitus (T2DM) induced by high-fat diet and low-dose streptozotocin (STZ). METHODS: A total of 52 SD male rats aged 15 months were randomly divided into normal control group (13) and high-fat group (39), and fed normal and high fat diets. After 8 weeks, the body weight of the high-fat group was higher 20% than that of the normal control group. After a small dose of STZ, the blood glucose level was ＞16.7 mmol/l, and the model was successfully established. The diabetic model group was randomly divided into a diabetic control group (DC, n=13), a diabetic chronic exercise group (DCE, n=13), and a diabetic acute exercise group (DAE, n=13). The DCE group underwent an 8-week swimming exercise and the DAE group performed a one-time swimming exercise. Blood lipids, blood glucose and serum insulin levels were measured, and the contents of fat PI3K, AKT and GLUT4 proteins were determined by Western blot method. RESULTS: The levels of body weight, blood lipids, blood glucose and insulin in the diabetic group were significantly higher than those in the normal control group (P＜0.01); high density liptein cholesterol(HDL-C) levels were decreased (P＜0.05), and the expressions of PI3K, AKT and GLUT4 protein in adipose tissue were decreased (P＜0.01). After 8 weeks of swimming training, the levels of body weight, blood lipids, blood glucose and insulin all were decreased significantly (P＜0.01); while the level of HDL-C was increased (P＜0.05), and the expressions of PI3K, AKT and GLUT4 protein were increased (P＜0.01). After acute exercise, the levels of blood lipids, blood glucose and insulin were decreased (P＜0.05); the level of HDL-C was increased (P＜0.05), and the expression levels of fat PI3K, AKT and GLUT4 were increased significantly (P＜0.05). CONCLUSION: ①High fat diet combined with low-dose STZ induced damage to the PI3K/AKT pathway in adipose tissue of T2DM rats reduced insulin sensitivity. ②Acute and chronic aerobic exercise can improve the disorder of glucose and lipid metabolism through PI3K/AKT pathway, and the chronic exercise is better than acute exercise.

[The effects of aerobic exercise on ERK1/2 activity in skeletal muscle of type 2 diabetic rats].

OBJECTIVE: To observe the effects of aerobic exercise on activity of extracellular signal-regulated kinase (ERK1/2) in skeletal muscle of type 2 diabetic rats and explore the prevention and control mechanism of aerobic exercise on type 2 diabetes. METHODS: Seventy five SD rats were randomly divided into:normal control group(CON) including 15 rats was fed with normal diet, diabetes control group 1(DC1), diabetes exercise group 1(DE1), diabetes control group 2(DC2), diabetes exercise group 2(DE2). Diabetes model group were fed with high-fatty and high-sugar diet. The diabetes model rats were fed with high-fatty and high-sugar diet for 8 weeks,.Diabetes group 2 rats were injected intraperitoneal streptozotocin(STZ)to induce type 2 diabetes. At the early stage of last swimming week, diabetes exercise group1 and diabetes control group 1 were injected with STZ (35 mg/kg) at the same time, After three days, if the level of blood glucose was ≥ 16.7mmol/L, the model was successful. After 8 week-interventions, all the rats were killed, the serum levels of insulin and the expression of ERK1/2 protein in skeletal muscle were determined. RESULTS: ①Compared with the normal control group, the levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterin(LDL-C), free fatty acid(FFA), fasting blood-glucose(FBG), fasting insulin(FIN) and insulin resistance index(HOMA-IR) were increased significantly in diabetes control group(P<0.05 or 0.01). However, the expression of ERK1/2 phosphorylation protein was decreased obviously in diabetes control group. The content of ERK1/2 protein was decreased obviously in diabetes control group 2 had (P<0.05). 2.After eight weeks' swimming, compared with the diabetes control group, the levels of TC,TG, FFA, LDL-C, FBG, FIN and HOMA-IR were decreased significantly in diabetes exercise group(P<0.05 or 0.01). At the same time, the expression of ERK1/2 phosphorylation protein was increased obviously in diabetes exercise group(P<0.05). CONCLUSIONS: Long-term aerobic exercise can improve the skeletal muscle ERK1/2 phosphorylation and insulin resistance of type 2 diabetic rats, thereby lowering blood glucose. It is probably one of the mechanisms to improve glucose metabolism disorders and insulin sensitivity.

[The Role of c-fos in the Production of Follicle-Stimulating Hormone and the Related Signal Transduction Pathways].

As an immediate early gene, c-fos plays a critical role in stimulating the synthesis and release of pituitary FSH via GnRH. To better understanding the mechanism how c-fos works in the transcription of FSHbeta under different frequency of pulsatile GnRH stimulation, this paper reviewed the signal trans- ductions initiated by c-fos in pituitary, which include cAMP pathway, MAPK pathway, Ca2+ /calmodulin-dependent kinases pathway and nuclear factor of activated T-cells (NFAT) pathway. It will be helpful for research in molecular targeted immunotherapy and eventually effective treatment to the infertility which resulted from defection or mutation of c-fos and c-fos related signal pathway elements.