Synergistic effect of endurance training and nettle leaf extract on the IDO1-KYN-AHR pathway homeostasis and inhibiting of liver toxicity in rats with STZ-induced diabetes.

Introduction: Diabetes adversely affects a number of hepatic molecular pathways, including the kynurenine (KYN) pathway. KYN is produced by indoleamine 2,3-dioxygenase (IDO) and activates the aryl hydrocarbon receptor (AHR). This study evaluated the effect of endurance training (EndTr) and nettle leaf extract (NLE) on the IDO1-KYN-AHR pathway in the livers of rats with streptozotocin-induced diabetes. Methods: We divided 48 rats into six groups: controls (Ct), treated with EndTr (EndTr), diabetes-induced (D), D treated with NLE (D + NLE), D treated with EndTr (D + EnTr), and D treated with EndTr and NLE (D + EndTr + NLE). EndTr, D + EnTr, and D + EndTr + NLE groups were subjected to training with running on treadmill for 8 weeks, 5 days per week, 25 min in first session to 59 min at last session with intensity of 55% to 65% VO2max. Using real-time PCR gene (Ahr, Cyp1a1, and Ido1) expressions and ELISA, malondialdehyde (MDA) and protein (IDO1, AHR, and CYP1A1) levels were determined in the liver samples. Results: A significant three-way interaction of exercise, nettle, and diabetes was observed on the all variables (P< 0.001). In particular, significant increases in blood glucose level (BGL), in gene and protein expression, and in MDA and KYN levels were observed in the liver samples of the D group versus the Ct group (P< 0.05). BGL and liver MDA levels were significantly lower in the D + EndTr and D + NLE groups than that in the D group. However, the D + EndTr + NLE group showed a more significant decrease in these factors (P< 0.05). In addition, liver KYN levels were significantly lower in the EndTr group compared with that in the Ct group as well as in the D + EndTr + NLE and D + EndTr groups compared with that in the D groups (P< 0.05). Whereas both the EndTr and D + NLE groups showed lower Ahr expression and AHR level compared with the Ct and D groups, respectively (P< 0.05), the D + EndTr + NLE group showed a higher significant reduction in the AHR level than the D group (P< 0.05). The Cyp1a1 expression and IDO1 level significantly decreased only in the D + EndTr + NLE group compared to that in the D group (P< 0.05). Conclusion: Overall, this study showed that the combination of EndTr and NLE may synergistically restore the imbalanced IDO1-KYN-AHR pathway in diabetic liver.

Comparison of moderate-intensity continuous training and high-intensity interval training effects on the Ido1-KYN-Ahr axis in the heart tissue of rats with occlusion of the left anterior descending artery.

Myocardial infarction (MI) affects many molecular pathways in heart cells, including the Ido1-KYN-Ahr axis. This pathway has recently been introduced as a valuable therapeutic target in infarction. We examined the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on the axis in the heart tissue of male Wistar rats with occluded left anterior descending (OLAD). Thirty rats (age 10-12 weeks, mean weight 275 ± 25 g) were divided into five groups with 6 animals: Control (Ct) group, MICT group, rats with OLAD as MI group, rats with OLAD treated with MICT (MIMCT group) and rats with OLAD treated with HIIT (MIHIIT group). Rats performed the training protocols for 8 weeks, 5 days a week. HIIT included 7 sets of 4 min running with an intensity of 85-90% VO2max and 3 min of recovery activation between sets. MICT included continuous running at the same distance as HIIT with an intensity of 50-60% VO2max for 50 min. The expressions of Ahr, Cyp1a1, and Ido1 were assayed by real-time PCR. Malondialdehyde (MDA) and Kynurenine levels, and AHR, CYP1A1, and IDO1 proteins were detected using ELISA. Data were analyzed using the ANOVA and MANOVA tests. Compared to the CT group, MI caused an increase in all studied factors, but only statistically significant (P < 0.05) for MDA and IDO1. With a greater effect of HIIT, both protocols significantly lowered the proteins expressions in the MIHIIT and MIMCT groups, compared with the MI group (P < 0.001). In healthy rats, only AHR protein significantly decreased in the MICT group compared to the Ct group (P < 0.05). HIIT and MICT protocols significantly reduced the gene and protein expression of Cyp1a1 (P < 0.05) and Ido1 (P < 0.01), and HIIT had a greater effect. In conclusion, both protocols were effective at reducing the levels of Ido1-Kyn-Ahr axis components and oxidative stress in the infarcted heart tissue and HIIT had a higher significant effect.

The association of dietary and lifestyle indices for hyperinsulinemia with odds of non-alcoholic fatty liver disease in Iranian adults: a case-control study.

BACKGROUND: Evidence on the association of insulinemic effects of dietary pattern and other lifestyle factors with the odds of non-alcoholic fatty liver disease (NAFLD) are limited. In the current study, we aimed to examine the association of the empirical dietary index for hyperinsulinemia (EDIH) and empirical lifestyle index for hyperinsulinemia (ELIH) index with the NAFLD odds in the adult population. METHODS: In the current case-control study, 120 cases of NAFLD and 240 controls aged 20-60 years were included. The ultrasonography test was used to determine NAFLD. We used a validated food frequency questionnaire to collect dietary data of individuals and determine the scores of EDIH. Also, we determined the ELIH score based on diet, body mass index, and physical activity. The odds ratio (OR) of NAFLD was calculated using logistic regression test across EDIH and ELIH tertiles. RESULTS: The mean ± SD age of subjects (53% men) were 41.8 ± 7.5 years. In the age and sex-adjusted model, there is a significant association between a higher ELIH score and higher odds of NAFLD (OR = 2.74;95%CI:1.51-4.96,Ptrend = 0.001). Also, based on the multivariable-adjusted model, after controlling for age and sex, smoking, SES, and dietary intake of energy a remarkable positive association was observed between the higher score of ELIH and the odds of NAFLD (OR = 2.70; 95%CI:1.46-5.01,Ptrend = 0.002). However, there is no significant relationship between the higher score of EDIH and NAFLD odds. CONCLUSIONS: Our results showed that the high insulinemic potential of lifestyle, determined by the ELIH score, can be related to an increased NAFLD odds. However, no significant association was found between higher EDIH score and odds of NAFLD.

The Effect of a High-intensity Interval Training on Plasma Vitamin D Level in Obese Male Adolescents.

BACKGROUND: The worldwide increasing vitamin D deficiency in adolescents is alarming. The effect of high-intensity trainings on adolescent health is not clear. OBJECT: This study aimed to examine the effect of a high-intensity interval training (HIIT) on plasma level of vitamin D in overweight male adolescents. MATERIALS AND METHODS: About 96 overweight students aged 12-16 years from two high schools participated in the study. The schools were randomly assigned to the intervention group (n = 52) and the control group (n = 44). For the intervention group, HIIT was performed 3 days per week for 8 weeks, while the control group was asked to walk outdoors at the same time. RESULTS: At the end of the study, the vitamin D level was increased to 1.21 ng/dl in the intervention group, whereas it decreased to 1.94 ng/dl in the control group (P = 0.003). CONCLUSION: About 8 weeks of HIIT improved plasma level of vitamin D in overweight male adolescents. More prolonged interventions consisted of both the sex and broader age ranges are warranted.

Application of multivariate longitudinal models in SIRT6, FBS, and BMI analysis of the elderly.

Objective: SIRT6 is a main regulator of metabolism and lifespan and its importance has been implicated in the prevention against aging-related diseases. The objective of this study was to examine the application of multivariate longitudinal models in SIRT6, FBS, and BMI analysis in the elderly men after eight weeks concurrent training with supplementation of l-arginine (l-Arg). Methods: Thirty two elderly men with mean age of 63.09 ± 3.71 years were randomly divided into four equal-sized groups (each n = 8); Exercise + supplement (ES) group; exercise + placebo (EP) group; supplement (S) group and control (C) group. The ES and EP groups performed the eight weeks of concurrent training, three sessions per week. Group ES and group S consumed 1000 mg of l-Arg per day at 8:00 pm. Measurements of biochemical variables were done by ELISA Reader method. For analytical purposes, we used the paired sample t-test and multivariate longitudinal modeling with generalized estimating equation (GEE) methodology. All analyses have been implemented in R-3.4.1. p Values less than .05 were considered statistically significant. Results: With respect to significant association between sirt6, FBS, and BMI, this study showed that synergy effect of training and supplementation was greater than the sum of their individual effects on SIRT6 (ß = 0.79, p < .001), FBS (ß = -5.56, p = .022), and BMI (ß = -3.89; p = .041). Also exercise alone had a significantly larger effect than supplementation alone on responses. Conclusions: It can be concluded that the joint usage of concurrent training and supplement of l-Arg for elderly men could improve the metabolism and body composition.

Impact of eight weeks endurance training on biochemical parameters and obesity-induced oxidative stress in high fat diet-fed rats.

PURPOSE: High-fat diets (HFD) feeding is an important risk factor for obesity that is accompanied with metabolic syndrome. Appropriate exercise is recommended for obesity prevention. The molecular mechanisms and cellular pathways activated in response to HFD and exercise are not well understood. The purpose of this study was to investigate the effect of 8 weeks endurance training on some plasma biochemical parameters and oxidative stress in HFD induced obese rats. METHODS: Twenty-eight male Wistar rats were randomly divided into 4 groups: the standard diet (SD) group, endurance training group with a standard diet (ESD), HFD group, and endurance training group with high-fat diet (EHFD). After 8 weeks, blood samples were taken by cardiac puncture and plasma were used for determination of biochemical parameters and oxidative stress biomarkers. RESULTS: HFD significantly increased malondialdehyde level and decreased the activities of superoxide dismutase, catalase, and glutathione S-transferase and the content of glutathione in the plasma. HFD also increased activities of aspartate transaminase, alanine transaminase, lactate dehydrogenase, as well as levels of total cholesterol, triglyceride and low-density-lipoprotein-cholesterol. However, endurance training showed protective effect on changes in these parameters. CONCLUSION: These findings suggested that HFD alters the oxidant-antioxidant balance, as evidenced by reduction in the antioxidant enzymes activities and glutathione level and enhanced lipid peroxidation. Endurance training can be beneficial for the suppression of obesity-induced oxidative stress in HFD rats through modulating antioxidant defense system and reduces the risk of obesity-associated diseases.

The effect of eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma.

OBJECTIVES: Consumption of high-fat foods is one of the major causes of obesity. Physical exercise is a strategy used to counteract obesity. The aim of this study was to investigate the effect of eight weeks endurance training and high-fat diet (HFD) on appetite-regulating hormones in rat plasma. MATERIALS AND METHODS: TWENTY EIGHT MALE WISTAR RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS: Control group with standard diet (CSD), endurance training with a standard diet (ESD), control group with high-fat diet (CHFD) and endurance training with high-fat diet (EHFD). Twenty-four hr after the last training session, the blood samples were obtained and analyzed for hormones levels. RESULTS: The significant increased weight gain and food intake and decreased plasma nesfatin-1 and PYY3-36 levels were observed in CHFD group, while exercise under the HFD antagonized these effects. There were no significant changes in ghrelin, insulin and leptin levels in different groups. CONCLUSION: These results suggest that exercise can prevent fattening effect of HFD. Probably, performing exercise makes a reduction of food intake and weight gain in rat via the increase in nesfatin-1 and PYY levels. However, further studies are necessary to understand the exact mechanisms involved in this field.