Betatrophin and Insulin Resistance.

Betatrophin (angiopoietin-like protein 8 (ANGPTL8)) is a hormone that was recently discovered in the human liver. Multiple homologous sequences have been detected in mammalian liver, white adipose, and brown adipose tissues. Betatrophin is crucial for the development of type 2 diabetes (T2D), insulin resistance, and lipid metabolism. Similar to the intake of insulin, thyroid hormones, irisin, and calories, betatrophin expression in the organism is usually attributed to energy consumption or heat generation. It can mediate the activity of lipoprotein lipase (LPL), which is the key enzyme of lipoprotein lipolysis. Due to its association with metabolic markers and the roles of glucose and lipid, the physiological function of betatrophin in glucose homeostasis and lipid metabolism can be more comprehensively understood. Betatrophin was also shown to facilitate pancreatic ß-cell proliferation in a mouse model of insulin resistance. There are also reports that demonstrate that betatrophin regulates triglycerides (TGs) in the liver. Therefore, the process of regulating the physiological function by betatrophin is complicated, and its exact biological significance remains elusive. This study provides a comprehensive review of the current research, and it discusses the possible physiological functions of betatrophin, and specifically the mechanism of betatrophin in regulating blood glucose and blood lipids.

Adiponectin Intervention to Regulate Betatrophin Expression, Attenuate Insulin Resistance and Enhance Glucose Metabolism in Mice and Its Response to Exercise.

Aims: Adiponectin stimulates mitochondrial biogenesis through peroxisome proliferator-activated receptor-coactivator1α (PGC-1α), a major regulator of mitochondrial biogenesis, and its effect on the genesis of insulin resistance is organ-specific. Expressed predominantly in fat and liver tissues, betatrophin is primarily involved in lipid metabolism, and could be a putative therapeutic target in metabolic syndrome and T2D. We hypothesized that the adiponectin pathway may regulate the production and/or secretion of betatrophin in liver. We aimed to determine whether exercise and adiponectin affect betatrophin to improve insulin resistance in mice. Methods: To investigate this hypothesis, we used wild-type C57BL/6 mice subjected to a high-fat diet, an exercise regimen, and i.p. injection of recombinant mouse adiponectin (Acrp30), and adiponectin knockout (Adipoq-/-) mice (C57BL/6 background) subjected to i.p. injection of Acrp30. Results: In Adipoq-/- mice, betatrophin levels in the plasma and liver were upregulated. In mice, plasma and liver betatrophin levels were significantly upregulated following a high-fat diet. Exercise and i.p. Acrp30 downregulated betatrophin levels and increased adiponectin mRNA and protein expression in the plasma and liver. The trend of change in PGC-1α and betatrophin levels in the liver was consistent. Conclusions/interpretation: Exercise reverses pathogenic changes in adiponectin and betatrophin levels in insulin-resistant mice. Exercise increased adiponectin levels and reduced betatrophin levels. Furthermore, exercise reduced betatrophin levels via adiponectin, which modulated the LKB1/AMPK/PGC-1α signaling axis but was not solely dependent on it for exerting its effects.

A cross-sectional comparative study on the effects of body mass index and exercise/sedentary on serum asprosin in male college students.

Adipocytes regulate the body's metabolism by secreting adipokines to maintain energy homeostasis. Asprosin is a new type of adipokine, and its relationship with obesity remains controversial. There are a few reports on the effect of long-term exercise on serum asprosin level. This study aimed to investigate the effects of body mass index (BMI) and exercise/sedentary habit on serum asprosin in male college students as well as the relationship between serum asprosin and body composition and related metabolic indicators and provided a basis for further exploration of the biological function of asprosin. Ninety-six male college students were classified into the sedentary habit group (SD; 48) and the special training experience group (ET; 48). Both groups included three subgroups of normal BMI, overweight, and obesity, with 16 people in each subgroup. One-way analysis of variance, analysis of covariance, and Pearson correlation analysis were performed. The results showed that serum asprosin levels in the obesity subgroup were significantly higher than those in the normal and overweight subgroups. Excluding BMI interference, there were no significant differences in serum asprosin between the SD and ET groups; however, there were significant differences in body composition, tumor necrosis factor-α, interleukin-6, and interleukin-10. Asprosin was positively correlated with BMI, body fat percentage, visceral fat area, fasting insulin, insulin resistance homeostasis model, total cholesterol, low-density lipoprotein, tumor necrosis factor-α, interleukin-6, and leptin levels and was negatively correlated with relative lean body mass, relative skeletal muscle mass, high-density lipoprotein, and interleukin-10, and adiponectin levels. In conclusion, serum asprosin is closely related to body weight, body composition, glucose and lipid metabolism, inflammatory response, and fat hormones. Long-term exercise training cannot prevent BMI increase from increasing serum asprosin level. If the influence of BMI is excluded, long-term exercise training does not affect serum asprosin.

Effects of exercise and dietary intervention on muscle, adipose tissue, and blood IRISIN levels in obese male mice and their relationship with the beigeization of white adipose tissue.

Background: Obesity is a growing problem worldwide, and newer therapeutic strategies to combat it are urgently required. This study aimed to analyze the effect of diet and exercise interventions on energy balance in mice and elucidate the mechanism of the peroxisome proliferator-activated receptor-gamma co-activator-1-alpha-IRISIN-uncoupling protein-1 (PGC-1α-IRISIN-UCP-1) pathway in the beigeization of white adipose tissue. Methods: Four-week-old male C57BL/6 mice were randomly divided into normal (NC) and high-fat diet (HFD) groups. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (OC), obesity diet control (OD), obesity exercise (OE), and obesity diet control exercise (ODE) groups. Mice in OE and ODE performed moderate-load treadmill exercises: for OD and ODE, the diet constituted 70% of the food intake of the OC group for 8 weeks. Results: Long-term HFD inhibits white adipose tissue beigeization by downregulating PGC-1α-IRISIN-UCP-1 in the adipose tissue and skeletal muscles. Eight weeks of exercise and dietary interventions alleviated obesity-induced skeletal muscle, and adipose tissue PGC-1α-IRISIN-UCP-1 pathway downregulation promoted white adipose tissue beigeization and reduced body adipose tissue. The effects of the combined intervention were better than those of single interventions. Conclusions: Diet and exercise intervention after obesity and obesity itself may affect the beigeization of WAT by downregulating/upregulating the expression/secretion of skeletal muscle and adipose PGC-1α-IRISIN, thereby influencing the regulation of bodyweight. The effects of the combined intervention were better than those of single interventions.

MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathway.

Mitochondrial-derived peptide (MOTS-c) has gained increasing attention as a promising therapeutic or prevention strategy for obesity and diabetes mellitus. MOTS-c targets the folate cycle, leading to an accumulation of 5-aminomidazole-4-carboxamide ribonucleotide (AICAR) as well as AMPK activation. AMPK is a well-known upstream regulator of the proliferation-activated receptor co-activator 1 (PGC-1α), which can improve mitochondrial biogenesis via co-transcriptional modifications. We hypothesized that AMPK can induce the expression of MOTS-c through PGC-1α. Our study aimed to explore whether MOTS-c and/or exercise can regulate MOTS-c expression, attenuate insulin resistance and enhance glucose metabolism both in vitro and in vivo. It was found that C2C12 myotubes exposed to Compound C (an AMPK inhibitor) had deceases in the protein and mRNA expressions of PGC-1α and MOTS-c. PGC-1α knockdown downregulated the protein and mRNA expressions of MOTS-c in C2C12 myotubes, whereas both PGC-1α overexpression and recombinant MOTS-c supplementation upregulated the protein and mRNA expressions of MOTS-c in C2C12 myotubes. Furthermore, the skeletal muscle and plasma levels of MOTS-c were markedly reduced in high-fat diet-induced obese mice. Treadmill training remarkably upregulated the protein levels of MOTS-c, PGC-1α and GLUT4, along with the phosphorylation levels of AMPK and ACC. Altogether, these results indicate that AMPK/PGC-1α pathway can mediate the secretion and/or production of MOTS-c in skeletal muscle, implying the possible roles of exercise intervention and recombinant MOTS-c in treating obesity and diabetes mellitus.

Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance.

BACKGROUND: Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis. METHODS: Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively. RESULTS: Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT. CONCLUSION: During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.

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.

Effect of Different Exercise Loads on Testicular Oxidative Stress and Reproductive Function in Obese Male Mice.

This study is aimed at investigating the effect of different exercise loads on the reproductive function of obese male mice and the underlying mechanisms. Male mice with high-fat diet-induced obesity were divided into obesity control (OC), obesity moderate-load exercise (OME), and obesity high-load exercise (OHE) groups. The OME and OHE groups were subjected to swimming exercise 5 days per week over a duration of 8 weeks, with the exercise load progressively increased to 2 h per day in the OME group and 2 h twice per day in the OHE group. In the OC group mice without exercise regimen, we observed a decrease in mRNA expression of antioxidant enzymes, increase in free radical products, upregulation of mRNA and protein expression of nuclear factor-κB and proinflammatory cytokines, inhibition of mRNA and protein expression of testosterone synthases, decrease in the serum testosterone level and sperm quality, and increase in sperm apoptosis. Although both moderate-load exercise and high-load exercise reduced body fat, only moderate-load exercise effectively alleviated obesity-induced oxidative stress, downregulated the expression of nuclear factor-κB and proinflammatory cytokines, and reversed the decrease in mRNA and protein expression of testosterone synthases, serum testosterone level, and sperm quality. These changes were not observed in the OHE group mice. Obesity-induced testicular oxidative stress and inflammatory response decreased testosterone synthesis and sperm quality. Moderate-load exercise alleviated the negative effect of obesity on male reproductive function by decreasing testicular oxidative stress and inflammatory responses. Although high-load exercise effectively reduced body fat, its effects on alleviating oxidative stress and improving male reproductive function were limited.

2D-Layered Ni-MgO-Al2 O3 Nanosheets for Integrated Capture and Methanation of CO2.

CO2 capture is an enabling technology for carbon conversion and storage; however, the high costs of the process have hindered its large-scale application so far. Therefore, new approaches for carbon abatement, particularly from diluted sources, are urgently needed. Herein, based on the adsorption and catalysis bifunctionality of 2D-layered Ni-O-Al2 O3 nanosheets, a two-step "capture and methanation" process is reported for the removal and utilization of CO2 , with no additional energy input for desorption being required. Continuous and nearly 100 % capture of CO2 was demonstrated at low temperatures (≤250 °C) and prolonged cycles. At isothermal conditions, the material could be fully regenerated with the production of methane, showing considerably higher time efficiency than temperature-swing and pressure-swing technologies. This strategy may pave a new way for CO2 reduction, providing a scalable connection between the power grid and the gas grid when H2 is used.

Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism.

To explore the role of nesfatin-1 in regulating male reproductive function during energy balance variation, we employed an obese mouse model which was first induced by a high-fat diet (HFD) and followed by interventions of a normal diet (ND) and/or moderate exercise, and then serum reproductive hormones of male mice, hypothalamic nucleobindin 2 (NUCB2)/nesfatin-1, inflammatory factors, and gonadotropin-releasing hormone (GnRH) levels were tested. Our findings showed that both serum nesfatin-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels and hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels were reduced, whereas, the mRNA and protein levels of hypothalamic tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, inhibitor kappa B kinase ß (IKKß), and nuclear factor (NF)-κB were increased in obese male mice. Diet, exercise, and diet combined with exercise interventions reversed the decreases in serum nesfatin-1, FSH, LH, and T levels; increased hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels; and reduced hypothalamic TNF-α, IL-1ß, IKKß, and NF-κB levels. These changes were accompanied by reduced adiposity, and these effects were more obvious in the diet combined with exercise group. Overall, our findings suggested that the hypogonadotropic hypogonadism associated with obesity may be induced by reduced hypothalamic NUCB2/nesfatin-1 levels, which attenuated the stimulatory effect on GnRH directly or indirectly by suppressing its anti-inflammatory effect in the brain. Diet and/or exercise interventions were able to alleviate the hypogonadotropic hypogonadism associated with obesity, potentially by increasing hypothalamic NUCB2/nesfatin-1 levels.

Effects of acute exercise and chronic exercise on the liver leptin-AMPK-ACC signaling pathway in rats with type 2 diabetes.

AIM: To investigate the effects of acute and chronic exercise on glucose and lipid metabolism in liver of rats with type 2 diabetes caused by a high fat diet and low dose streptozotocin (STZ). METHODS: Animals were classified into control (CON), diabetes (DC), diabetic chronic exercise (DCE), and diabetic acute exercise (DAE) groups. RESULTS: Compared to CON, the leptin levels in serum and liver and ACC phosphorylation were significantly higher in DC, but the levels of liver leptin receptor, AMPK α 1/2, AMPK α 1, and ACC proteins expression and phosphorylation were significantly lower in DC. In addition, the levels of liver glycogen reduced significantly, and the levels of TG and FFA increased significantly in DC compared to CON. Compared to DC, the levels of liver AMPK α 1/2, AMPK α 2, AMPK α 1, and ACC phosphorylation significantly increased in DCE and DAE. However, significant increase of the level of liver leptin receptor and glycogen as well as significant decrease of the level of TG and FFA were observed only in DEC. CONCLUSION: Our study demonstrated that both acute and chronic exercise indirectly activated the leptin-AMPK-ACC signaling pathway and increased insulin sensitivity in the liver of type 2 diabetic rats. However, only chronic and long-term exercise improved glucose and lipid metabolism of the liver.

Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes.

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and ß cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus. As a result, blood glucose, triglyceride, total cholesterol, and free fatty acid were significantly increased, whereas insulin level progressively declined in diabetic rats. Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC). Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1. But acute exercise only increased LKB1 expression. In particular, exercise reversed the changes in protein kinase C (PKC)ζ/λ phosphorylation, and PKCζ phosphorylation and expression. Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged. Chronic exercise elevated Akt (Thr(308)) and (Ser(473)) and AS160 phosphorylation. Finally, we found that exercise increased peroxisome proliferator-activated receptor-γ coactivator 1 (PGC1) mRNA expression in the soleus of diabetic rats. These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle. These data help explain the mechanism how exercise regulates glucose homeostasis in diabetic rats.

[Effects of exercise on expression and phosphorylation of PI3K and PKB in insulin signaling in the skeletal muscles of type 2 diabetic rats].

OBJECTIVE: To investigate the effect of exercise on the expressions of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (PKB) phosphorylation, protein and glucose transport proteins (GLUT4) at both the protein and mRNA levels in the skeletal muscles of type 2 diabetic rats. METHODS: Thirty male SD rats were randomly divided into control group with normal diet feeding, diabetic group and diabetic exercise group with high-fat diet feeding. After 8 weeks of the high-fat diet, each rat received an intraperitoneal injection of streptozotocin (STZ, 30 mg/kg). Three weeks after the injection, the rats were rated for the presence of diabetes, and the rats in the exercise groups took swimming training for 4 weeks; all the groups maintained their assigned diets. The gastrocnemius of all the rats were dissected 48 h after the last training session. Western blotting was applied to detect the phosphorylation and protein expression of PI3K and PKB and the protein expression of GLUT4. The expression of GLUT4 mRNA was determined by RT-PCR. RESULTS: Compared with the diabetic group, the diabetic rats in the exercise group showed significantly increased protein expression and phosphorylation of PKB (P<0.05) and elevated GLUT4 protein and mRNA expressions in the skeletal muscles (P<0.01, P<0.05). CONCLUSION: Exercise training can modulates insulin signal transduction through the protein expression and phosphorylation of the protein kinase to promote glucose uptake in the skeletal muscle of type 2 diabetic rats.

[Effects of exercise on JNK phosphorylation and expression in skeletal muscle of rats].

AIM: To investigate the effects of exercise on JNK phosphorylation, protein and gene expression. METHODS: Male rats were randomly divided into control and trained groups. The trained rats were submitted to 1 h or 1.5 h of exercise daily and had a fragment of their excised gastrocenemius muscle, 24 h or 48 h after the last training session. The train lasted for 7 weeks. The changes in the expressions of JNK and p-JNK were determined by Western blotting. The expression of JNK mRNA was determined by RT-PCR. RESULTS: Glucose tolerance test found that blood insulin concentration was decreased with exercise training. Exercise led to a marked increase in p-JNK of trained groups 24 hours after exercise in rats that exercised for 1 hour per day and 24 and 48 hours after the exercise in those that exercised for 1.5 hours per day as compared with controls, and the protein expression of JNK significantly increased 24 and 48 hours after the exercise in rats that exercised for 1.5 hours per day. JNK mRNA was increased by exercise 1.5 h/d, 24 h after the last training session. CONCLUSION: Exercise could increase muscle responsiveness to insulin, improving the total JNK and p-JNK and mRNA expression.

Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia.

OBJECTIVE: To observe the effects of lead on levels of phosphorylated extracellular signal regulated kinase (p-ERK) in the cytoplasm of primary cultures of rat astroglial cells and the possible protective effect of basic fibroblast growth factor (bFGF) on lead-induced effects. METHODS: The primary astroglia cells from 1~6 d old Wistar rats were cultured. The cells pretreated with the MEK1 (mitogen-activated protein kinase kinase 1) inhibitor PD98059 and bFGF, respectively, were exposed to Pb acetate of different concentrations for different times. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) methods were used to detect the protein and mRNA expressions of ERK. RESULTS: mRNA expression for ERK peaked 15 min after initiation of lead exposure (P<0.05) and protein expression of p-ERK peaked at 30 min (P<0.05). ERK mRNA levels and p-ERK protein levels returned to baseline after 60 and 120 min of lead exposure, respectively (P>0.05). The increase in p-ERK levels in lead-treated cells could be inhibited by PD098059. Activation of ERK in the cells by lead was prevented by pretreatment with bFGF. Total ERK protein levels did not change under the same experimental conditions (P>0.05). CONCLUSION: Low-level lead exposure resulted in transient activation of ERK through the MEK pathway, which then returned to basal levels in the continued presence of lead. Exogenous bFGF protected ERK signaling components in astroglia from lead poisoning.

[Effects of endurance exercise on ERK1/2 phosphorylation and expression in skeletal muscle of rats].

AIM: To investigate the effects of exercise on phosphorylated and total ERK1/2, and mRNA of ERK2. METHODS: Male rats were randomly divided into control and trained groups. The trained rats were submitted to 1 h or 1.5 h of exercise daily and had a fragment of their excised gastroenemius muscle, 24 h or 48 h after the last training session. The train lasted for 7 weeks. The changes in the expressions of ERK1/2 and p-ERK1/2 were determined by Western blotting.The expression of ERK2 mRNA was determined by RT-PCR. RESULTS: Exercise led to a marked increase in p-ERK1/2 of trained groups as compared with controls, and increased ERK1/2 protein expression of training 1.5 h/d, 24 h and 48 h after the last training session. ERK2 mRNA was increased by exercise 1 h/d, 24 h and exercise 1.5 h/d, 24 h and 48 h after the last training session. Glucose tolerance test found that blood insulin concentration was decreased with exercise training. CONCLUSION: Endurance exercise could increase muscle responsiveness to insulin by improving the total ERK1/2 and p-ERK1/2, ERK2 mRNA expression.