The adaptations induced by Estrogen Related Receptor alpha (ERRα) disruption and exercise training on healthy and diabetic rat�s liver

Diabetes is a widespread metabolic disorder that needs specific management and researchers focused on exercise training and pharmacological interventions for diabetes management. Endurance training (ET) and ERRα gained attention as a potential therapeutic target for diabetes management. We investigated ET and ERRα inhibition effects on the expression of SIRT1 and AMPK in healthy and STZ-induced diabetic rats� liver. Fifty-six Wistar rats were divided into 8 groups as follows (n = 7); group 1, control with no treatment; group 2, diabetic control group that received a single dose of STZ; group 3, ERRα inhibited group that received XCT 790; group 4, endurance training (ET); group 5, diabetic rats with ERRα inhibition; group 6, diabetic rats that performed ET; group 7, ERRα inhibition and ET; and group 8, diabetic rats with ERRα inhibition and performed ET. After 4 weeks, the animals were sacrificed and the liver was used for Real-Time PCR and Western blotting. Our results showed that ET significantly increased AMPK and SIRT1 gene and protein, and ERRα gene expression in healthy and diabetic rats compared to healthy and diabetic control groups. ERRα inhibition increased AMPK, SIRT1, SREBP-1c and ACC expression compared to control and ET groups. In healthy and diabetic rats, the combination of ERRα inhibition and ET significantly increased AMPK, SIRT1, SREBP-1c and ACC expression compared to healthy and diabetic control animals. Briefly, the combination of ET and ERRα disruption probably can be considered as a potential therapeutic intervention in diabetes but this hypothesis needs more evaluation to be cleared. © 2020, Institute of Molecular Biology, Slovak Academy of Sciences

Effect of the combination of training and errα inhibition on liver metabolism by modulation of pdk4 and lxr-α expression in stz-induced diabetic and healthy rats

Diabetes is a public health problem that affects life quality. Exercise training (ET) and controlled dietary habits improve metabolic diseases such as diabetes. The mechanisms by which exercise training ameliorate metabolic diseases are not fully clear. We designed the current study to evaluate the combination of ERRα suppression and ET effects on the expression of LXR-α, PDK4, and PPARα in healthy and STZ-induced diabetic rats. Fifty-six male Wistar rats were divided into 8 groups (n = 7) as follows; control, diabetic control (a single dose of 45 mg/kg of STZ), ERRα inhibition group (received 0.48 mg/kg of XCT790), endurance training, diabetic rats which received XCT790, diabetic rats which performed endurance training, rats which received XCT790 and performed endurance training, and diabetic rats which received XCT790 and also performed endurance training. Expression of the target gene and protein was carried out on the liver tissue. Our results showed that ET significantly increased PDK4, PPARα, and ERRα expression. ERRα suppression significantly increased LXR-α and PDK4 expression in healthy rats compared to the healthy control group. In the diabetic group with ERRα suppression, LXR-α expression significantly upregulated. The combination of ET and ERRα suppression did not change LXR-α expression compared to healthy and diabetic groups (CTL/ERR), but the expression of PDK4, PPARα, and ERRα was significantly upregulated. © 2020 by the authors

The effects of pdk4 inhibition on ampk protein levels and pgc-1α gene expression following endurance training in skeletal muscle of wistar rats

There are regulatory networks in cells which surveil the physiological and environmental states. These cellular regulations are conducted through gene expression modulation. Skeletal muscle is able to adapt shortly and produce ATP at different conditions. AMPK (AMP-activated protein kinase) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) are important regulators of cellular energy homeostasis. We designed this study to examine the effects of interactions between endurance training­ and PDK4 (pyruvate dehydrogenase kinase 4) inhibition on AMPK and PGC-1α expression in rat skeletal muscle. Thirty-two male Wistar rats were randomly selected and divided into 4 groups (n = 8); Group 1 control which did not receive any treatment, Group 2 received dichloroacetic acid (DCA) (150 mg/kg/day), Group 3 (endurance training group), Group 4 which received DCA and performed endurance training. AMPK protein expression, PDK4 and PGC-1α gene expression were measured by western blotting and real-time PCR, respectively. Our data showed that PDK4 inhibition caused AMPK protein elevation. Endurance training­ (group 2) and PDK4 inhibition (group 4) induce significant enhancement of PGC-1α gene expression compared to control group. The group which received DCA showed significant elevation of PDK4 gene expression compared to control group (P = 0.001), also other two groups (groups 2 & 3) showed significant elevation of PDK4 gene expression compared to control (P = 0.006). It seems that the combination of endurance training and PDK4 inhibition by up-regulation of PGC-1α expression, effectively improves energy state and performance in skeletal muscle

L-carnitine administration effects on AMPK, APPL1 and PPARγ genes expression in the liver and serum adiponectin levels and HOMA-IR in type 2 diabetes rat model induced by STZ and nicotinamide

Diabetes is a chronic disease and public health problem globally. L-Carnitine is synthesized in the liver, promotes fatty acids oxidation and currently is used as a supplement against weight gain. Carnitine level is found to be reduced in diabetic patients and to be beneficial as a supplement at diabetes, but the mechanisms of this effect is not fully understood. Therefore, we evaluated the oral L-carnitine supplemen-tation on expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPARγ), adaptor protein APPL1 genes in the liver and insulin and adiponectin levels in the serum of diabetic rats. Rats were randomly divided into three groups (n = 8) as follow: group 1 � control without any treatment, group 2 � diabetic control rats which received STZ (45 mg/kg) and nicotinamide (200 mg/kg) by i.p. injection, group 3 � diabetic rats which received 600 mg/kg/day carnitine orally for 35 days. It was found that L-carnitine supplementation reduced the level of fasting glucose compared to that in control and diabetic groups (p = 0.001, p = 0.0001 respectively) and increased adiponectin level compared to diabetic nontreated rats (p = 0.0001). Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly increased in the diabetic group and reduced in the group that received L-carnitine. These promising beneficial effect of L-carnitine on the type 2 diabetes in rats� model was shown to be conducted through the up-regulation of AMPK, PPARγ and APPL1 genes expression in the liver and elevation of serum adiponectin level. © 2020 Shahouzehi B. et al

L-Carnitine different doses affect serum and pancreas tissue Antioxidative defense and histopathology in STZ-induced diabetic rats

Diabetes mellitus is a global health issue that affects life expectancy and quality. In diabetic patients, the oxidation status is increased which has detrimental effects against homeostasis. L-carnitine showed anti-oxidative effects in different tissues, and also it was reported that L-carnitine levels reduced in patients with diabetes. In this study, we examined the administration of different doses of L-carnitine on antioxidants status in diabetic rats� serum and pancreas. Forty-eight male rats (200 ± 10 g weight) were randomly selected and divided into 6 groups (n = 8) as follow; Group I, untreated control, group II, Diabetic control, group III-VI, diabetic rats which received 50, 100, 200 and 300 mg/kg/day L-carnitine by intraperitoneal injection for 35 days, respectively. At the end of the study, blood samples and pancreas tissue were collected and histopathology and anti-oxidant status were measured. Our results showed that antioxidative capacity was reduced in the diabetic rats. Between different L-carnitine doses, 300 mg/kg/day of L-carnitine showed significant effects than other doses. The highest dose of L-carnitine (300 mg/kg/day) in this study, significantly increased TAS (Total Antioxidant Status), SOD (Superoxide Dismutase) and GPX (Glutathione Peroxidase) levels in the pancreas and serum. Also, it improved pancreas histopathology compared to the diabetic control group. We conclude that L-carnitine administration has protective effects on the pancreas and serum of STZ-induced diabetic rats, and exerts these beneficial effects through hypoglycemic and antioxidant actions. © 2020, Institute of Molecular Biology, Slovak Academy of Sciences

The effects of endurance training and estrogen-related receptor α disruption on mitofusin 1 and 2, GLUT2, PPARβ/δ and SCD1 expression in the liver of diabetic rats

Diabetes is a progressive and metabolic disease with a high prevalence throughout the world. Physical activity is considered as an intervention to improve diabetes. Intervention such as estrogen-related receptor α (ERRα) inhibition is considered as a new way to manage diabetes. In current study, we examined ERRα inhibition along with exercise training (ET) on the gene expression of mitofusin 1 (MFN1), MFN2, glucose transporter 2 (GLUT2), peroxisome proliferator-activated receptor beta or delta (PPARβ/δ), and stearoyl-CoA desaturase 1 (SCD1) in rat liver. The animals were divided into 8 groups (n = 7); 1, Control (CTL) 2, Diabetes (D) 3, ERRα inhibition (ERRI) 4, Endurance Training (ET) 5, Diabetes+ERRα inhibition (D+ERRI) 6, Diabetes+Endurance training (D+ET) 7, Endurance Training+ERRα inhibition (ET+ERRI) 8, Diabetes+Endurance Training+ERRα inhibition (D+ET+ERRI). The liver tissues were used for Real-Time PCR. The results showed that ET significantly increased PPARδ, MFN1 and, MFN2 expression in control rats compared to D group. In ERRI group, SCD1, GLUT2, MFN1 and MFN2 gene expression was increased compared to CTL and DM group. In CTL and D rats, the combination of ERRα inhibition and ET significantly and additively increased MFN1, MFN2, and GLUT2 expression. Overall, the combination of ET and ERRα inhibition probably can be considered as a potential therapeutic intervention for treatment of metabolic diseases including diabetes and cardiovascular disease. © 2020 Shahouzehi B. et al

The effect of high-intensity interval training and l-carnitine on the expression of some pro-inflammatory genes in the liver and cardiac tissues of rats

Background: Inflammation is characterized by interactions between cytokines and inflammatory pathogens. Cytokines are glycoproteins involved in inflammation. Exercise training and physical activity are associated with a healthy lifestyle. In the current study, we aimed to determine the effects of high intensity interval training (HIIT) and L-Carnitine (LCAR) on the expression of genes involved in inflammation and inflammatory pathways in the liver and heart of rats. Method: Thirty-two male Wistar rats were randomly divided into the four groups (n = 8): 1. Untreated control group, 2. LCAR group (received 200 mg/kg LCAR daily), 3. HIIT group (performed high intensity interval training), 4. Exercise training + LCAR. Results: The results of our study showed that HIIT + LCAR significantly reduced the expression of IL-1β in the liver compared to the HIIT group (p = 0.038). The combination of HIIT and LCAR decreased IL-6 expression in the liver tissue compared to the control (p <0.001), LCAR (p <0.001), and HIIT (p = 0.002) groups. The HIIT + LCAR group decreased Cox 2 gene expression in the liver tissue compared to the untreated control group (p <0.001), and LCAR group (p = 0.007). The combination of HIIT and LCAR reduced IL-1β expression in the cardiac tissue compared to the untreated control (p <0.001), LCAR (p = 0.034), and HIIT (p = 0.041) groups. The combination of HIIT and LCAR increased IL-6 expression in the cardiac tissue compared to the other three groups (p <0.001). Conclusion: According to the obtained results, HIIT combined with LCAR administration is very useful in reducing the expression of pro-inflammatory genes in the heart and liver tissues. © 2021, Kerman University of Medical Sciences. All rights reserved

Effect of L-carnitine administration on serum insulin and adiponectin levels, and AMPK, APPL1 and PPARγ gene expression in STZ-induced diabetic rat liver

Diabetes is considered as a metabolic disease in which insulin secretion and functions are disturbed and characterized by hyperglycemia. L-carnitine is synthesized in most mammals and plays critical role in fatty acid oxidation and energy production. Data about the L-carnitine hypoglycemic effects are controversial. We evaluated long-term oral L-carnitine administration effects on blood glucose, insulin and adiponectin levels, as well as expression of AMPK, APPL1 and PPARγ genes in liver of STZ-induced diabetic rats. Group 1 (control), did not receive any treatment, group 2 received 50 mg/kg STZ by i.p injection, group 3 received single dose of 50 mg/kg STZ by i.p injection and also 600 mg/kg/day L-carnitine orally for 5 weeks. Our results showed that L-carnitine long-term oral supplementation significantly reduced blood glucose and normalized insulin levels in diabetic rats. Also, we found that L-carnitine significantly increased AMPK and APPL1 expression, and showed a mild elevation of PPARγ expression. In sum, we suggest that long-term L-carnitine supplementation has beneficial effects on diabetic rats which showed hypoglycemic effects. Probably the beneficial effects of L-carnitine are contributed to the upregulation of insulin sensitizers such as AMPK and adiponectin