scholarly journals Protective Effect of Jiang Tang Xiao Ke Granules against Skeletal Muscle IR via Activation of the AMPK/SIRT1/PGC-1α Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Ying Bai ◽  
Jiacheng Zuo ◽  
Xin Fang ◽  
Rufeng Ma ◽  
Tian Tian ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
C2c12 Cells ◽  
Muscle Performance ◽  
Diabetic Mice ◽  
Skeletal Muscle Insulin Resistance ◽  
Reduced Body ◽  
Underlying Mechanisms

The Jiang Tang Xiao Ke (JTXK) granule is a classic Chinese herbal formula that has been put into clinical use in the treatment of type 2 diabetes mellitus for decades. However, whether its ability to ameliorate skeletal muscle insulin resistance (IR) is through modulation of the AMPK/SIRT1/PGC-1α signaling pathway remains unknown. Therefore, we aimed to investigate the effects of JTXK granules on IR in skeletal muscle of high-fat diet-induced diabetic mice and C2C12 cells and analyze the underlying mechanisms. In the present study, we showed that JTXK granules attenuated body weight gain, reduced body fat mass, improved body lean mass, and enhanced muscle performance of diabetic mice. JTXK granules also improved glucose metabolism and skeletal muscle insulin sensitivity and partially reversed abnormal serum lipid levels, which might be related to the regulation of the AMPK/SIRT1/PGC-1α pathway, both in skeletal muscle tissue of diabetic mice and in C2C12 cells. Furthermore, drug-containing serum of JTXK granules was capable of enhancing glucose uptake and mitochondrial respiration in C2C12 cells, and AMPKα was proven to be closely involved in this process. Taken together, these results suggest that the JTXK granule ameliorates skeletal muscle IR through activation of the AMPK/SIRT1/PGC-1α signaling pathway, which offers a novel perspective of this formula to combat IR-related metabolic diseases.

scholarly journals TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle

2015 ◽  
Vol 224 (3) ◽  
pp. 303-313 ◽  
Author(s):  
Jonathan M Mudry ◽  
Julie Massart ◽  
Ferenc L M Szekeres ◽  
Anna Krook
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Glycogen Synthesis ◽  
C2c12 Cells ◽  
Acid Oxidation ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Intact Mouse ◽  
Mouse Muscle ◽  
The Impact

TWIST proteins are important for development of embryonic skeletal muscle and play a role in the metabolism of tumor and white adipose tissue. The impact of TWIST on metabolism in skeletal muscle is incompletely studied. Our aim was to assess the impact of TWIST1 and TWIST2 overexpression on glucose and lipid metabolism. In intact mouse muscle, overexpression of Twist reduced total glycogen content without altering glucose uptake. Expression of TWIST1 or TWIST2 reducedPdk4mRNA, while increasing mRNA levels ofIl6,Tnfα, andIl1β. Phosphorylation of AKT was increased and protein abundance of acetyl CoA carboxylase (ACC) was decreased in skeletal muscle overexpressing TWIST1 or TWIST2. Glycogen synthesis and fatty acid oxidation remained stable in C2C12 cells overexpressing TWIST1 or TWIST2. Finally, skeletal muscle mRNA levels remain unaltered inob/obmice, type 2 diabetic patients, or in healthy subjects before and after 3 months of exercise training. Collectively, our results indicate that TWIST1 and TWIST2 are expressed in skeletal muscle. Overexpression of these proteins impacts proteins in metabolic pathways and mRNA level of cytokines. However, skeletal muscle levels of TWIST transcripts are unaltered in metabolic diseases.

scholarly journals Spatholobus suberectus Exhibits Antidiabetic Activity In Vitro and In Vivo through Activation of AKT-AMPK Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Peijun Zhao ◽  
Md Badrul Alam ◽  
Seok-hyun Lee ◽  
Young-Jun Kim ◽  
Seul Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
C2c12 Cells ◽  
Peripheral Tissue ◽  
Postprandial Blood Glucose ◽  
Signaling Cascade ◽  
Diabetic Mice ◽  
Enzyme Expression ◽  
Spatholobus Suberectus

Glucose deposition in peripheral tissue is an important parameter for the treatment of type 2 diabetes mellitus. The aim of this study was to investigate the effects of Spatholobus suberectus (Ss) on glucose disposal in skeletal muscle cells and additionally explore its in vivo antidiabetic potential. Treatment of ethanolic extract of S. suberectus (EeSs) significantly enhanced the glucose uptake, mediated through the enhanced expression of GLUT4 in skeletal muscle via the stimulation of AKT and AMPK pathways in C2C12 cells. Moreover, EeSs have potential inhibitory action on α-glucosidase activity and significantly lowered the postprandial blood glucose levels in STZ-induced diabetic mice, associated with increased expression of GLUT4 and AKT and/or AMPK-mediated signaling cascade in skeletal muscle. Furthermore, administration of EeSs significantly boosted up the antioxidant enzyme expression and also mitigated the gluconeogenesis enzyme such as PEPCK and G-6-Pase enzyme expression in liver tissue of STZ-induced diabetic mice model. Collectively, these findings suggest that EeSs have a high potentiality to mitigate diabetic symptoms through stimulating glucose uptake in peripheral tissue via the activation of AKT and AMPK signaling cascade and augmenting antioxidant potentiality as well as blocking the gluconeogenesis process in diabetic mice.

scholarly journals Effects of gut microbiota on leptin expression and body weight are lessened by high-fat diet in mice

2020 ◽  
Vol 124 (4) ◽  
pp. 396-406 ◽  
Author(s):  
Hongyang Yao ◽  
Chaonan Fan ◽  
Xiuqin Fan ◽  
Yuanyuan Lu ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
High Fat ◽  
Hepatic Expression ◽  
Reduced Body ◽  
Expression Of Genes ◽  
Underlying Mechanisms ◽  
Leptin Expression

AbstractAberration in leptin expression is one of the most frequent features in the onset and progression of obesity, but the underlying mechanisms are still unclear and need to be clarified. This study investigated the effects of the absence of gut microbiota on body weight and the expression and promoter methylation of the leptin. Male C57 BL/6 J germ-free (GF) and conventional (CV) mice (aged 4–5 weeks) were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for 16 weeks. Six to eight mice from each group, at 15 weeks, were administered exogenous leptin for 7 d. Leptin expression and body weight gain in GF mice were increased by NFD with more CpG sites hypermethylated at the leptin promoter, whereas there was no change with HFD, compared with CV mice. Adipose or hepatic expression of genes associated with fat synthesis (Acc1, Fas and Srebp-1c), hydrolysis and oxidation (Atgl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was lower, and hypothalamus expression of Pomc and Socs3 was higher in GF mice than levels in CV mice, particularly with NFD feeding. Exogenous leptin reduced body weight in both types of mice, with a greater effect on CV mice with NFD. Adipose Lep-R expression was up-regulated, and hepatic Fas and hypothalamic Socs3 were down-regulated in both types of mice. Expression of fat hydrolysis and oxidative genes (Atgl, Hsl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was up-regulated in CV mice. Therefore, the effects of gut microbiota on the leptin expression and body weight were affected by dietary fat intake.

scholarly journals Cinchonine Prevents High-Fat-Diet-Induced Obesity through Downregulation of Adipogenesis and Adipose Inflammation

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sung A. Jung ◽  
Miseon Choi ◽  
Sohee Kim ◽  
Rina Yu ◽  
Taesun Park
Keyword(s):  
High Fat Diet ◽  
Body Weight Gain ◽  
Signaling Cascades ◽  
Toll Like Receptor ◽  
High Fat ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Toll Like Receptor 2 ◽  
Underlying Mechanisms ◽  
Adipose Inflammation

Cinchonine (C19H22N2O) is a natural compound of Cinchona bark. Although cinchonine's antiplatelet effect has been reported in the previous study, antiobesity effect of cinchonine has never been studied. The main objective of this study was to investigate whether cinchonine reduces high-fat-diet- (HFD-) induced adipogenesis and inflammation in the epididymal fat tissues of mice and to explore the underlying mechanisms involved in these reductions. HFD-fed mice treated with 0.05% dietary cinchonine for 10 weeks had reduced body weight gain (−38%), visceral fat-pad weights (−26%), and plasma levels of triglyceride, free fatty acids, total cholesterol, and glucose compared with mice fed with the HFD. Moreover, cinchonine significantly reversed HFD-induced downregulations of WNT10b and galanin-mediated signaling molecules and key adipogenic genes in the epididymal adipose tissues of mice. Cinchonine also attenuated the HFD-induced upregulation of proinflammatory cytokines by inhibiting toll-like-receptor-2- (TLR2-) and TLR4-mediated signaling cascades in the adipose tissue of mice. Our findings suggest that dietary cinchonine with its effects on adipogenesis and inflammation may have a potential benefit in preventing obesity.

scholarly journals RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Mei Han ◽  
Lianghui You ◽  
Yanting Wu ◽  
Nan Gu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Palmitic Acid ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Metabolic Diseases ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
C2c12 Myotubes ◽  
Insulin Resistant

Abstract Insulin resistance (IR) has been considered as the common pathological basis and developmental driving force for most metabolic diseases. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators in modulation of glucose and lipid metabolism. However, the comprehensive profile of lncRNAs in skeletal muscle cells under the insulin resistant status and the possible biological effects of them were not fully studied. In this research, using C2C12 myotubes as cell models in vitro, deep RNA-sequencing was performed to profile lncRNAs and mRNAs between palmitic acid-induced IR C2C12 myotubes and control ones. The results revealed that a total of 144 lncRNAs including 70 up-regulated and 74 down-regulated (|fold change| > 2, q < 0.05) were significantly differentially expressed in palmitic acid-induced insulin resistant cells. In addition, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases revealed that the target genes of the differentially expressed lncRNAs were significantly enriched in fatty acid oxidation, lipid oxidation, PPAR signaling pathway, and insulin signaling pathway. Moreover, Via qPCR, most of selected lncRNAs in myotubes and db/db mice skeletal muscle showed the consistent expression trends with RNA-sequencing. Co-expression analysis also explicated the key lncRNA–mRNA interactions and pointed out a potential regulatory network of candidate lncRNA ENSMUST00000160839. In conclusion, the present study extended the skeletal muscle lncRNA database and provided novel potential regulators for future genetic and molecular studies on insulin resistance, which is helpful for prevention and treatment of the related metabolic diseases.

scholarly journals Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression

2021 ◽  
Author(s):  
Byung-Hyun Park ◽  
Mi-Young Song ◽  
Chang Yeob Han ◽  
Young Jae Moon ◽  
Eun Ju Bae
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Molecular Target ◽  
Muscle Performance ◽  
Specific Gene ◽  
Genetic Inactivation ◽  
Slow Fiber ◽  
Slow Twitch ◽  
Exercise Endurance

Abstract Expanding the exercise capacity of skeletal muscle is an emerging strategy to combat obesity-related metabolic diseases and this can be achieved by shifting skeletal muscle fibers toward slow-twitch oxidative type. Here, we report that Sirt6, an anti-aging histone deacetylase, is critical in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. Genetic inactivation of Sirt6 in skeletal muscle reduced while its transgenic overexpression increased mitochondrial oxidative capacity and exercise performance in mice. Mechanistically, we show that Sirt6 downregulated Sox6, a key repressor of slow fiber specific gene, by increasing the transcription of CREB. Sirt6 expression is elevated in chronically exercised humans and mice treated with an activator of Sirt6 showed an increase in exercise endurance as compared to exercise-trained controls. Thus, the current study identifies Sirt6 as a new molecular target for reprogramming myofiber composition toward the oxidative type and for improving muscle performance.

scholarly journals TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Barbara Toffoli ◽  
Federica Tonon ◽  
Veronica Tisato ◽  
Giorgio Zauli ◽  
Paola Secchiero ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Therapeutic Potential ◽  
Myogenic Differentiation ◽  
Body Weight Gain ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Acid Oxidation ◽  
Skeletal Muscle Differentiation ◽  
Akt Phosphorylation

AbstractTNF-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptosis in cancer cells but not in normal ones, where its effects remain to be fully understood. Previous studies have shown that in high-fat diet (HFD)-fed mice, TRAIL treatment reduced body weight gain, insulin resistance, and inflammation. TRAIL was also able to increase skeletal muscle free fatty acid oxidation. The aim of the present work was to evaluate TRAIL actions on skeletal muscle. Our in vitro data on C2C12 cells showed that TRAIL treatment significantly increased myogenin and MyHC and other hallmarks of myogenic differentiation, which were reduced by Dr5 (TRAIL receptor) silencing. In addition, TRAIL treatment significantly increased AKT phosphorylation, which was reduced by Dr5 silencing, as well as glucose uptake (alone and in combination with insulin). Our in vivo data showed that TRAIL increased myofiber size in HFD-fed mice as well as in db/db mice. This was associated with increased myogenin and PCG1α expression. In conclusion, TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake. These data shed light onto a pathway that might hold therapeutic potential not only for the metabolic disturbances but also for the muscle mass loss that are associated with diabetes.

scholarly journals Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1360
Author(s):  
Kah Heng Yap ◽  
Gan Sook Yee ◽  
Mayuren Candasamy ◽  
Swee Ching Tan ◽  
Shadab Md ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Mitochondrial Respiration ◽  
Consumption Rate ◽  
Tolerance Test ◽  
Insulin Signaling Pathway ◽  
Diabetic Mice ◽  
Ppar Γ

Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg/kg), metformin (200 mg/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (p < 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1α) and protein (AMPK, p-AMPK, PPAR-γ and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK/SIRT1/PGC-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.

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