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Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle.

ABSTRACT: Background:Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice. Materials and methods:Sixteen male C57BL/6 mice were divided into two experimental groups, including control and type 2 diabetic mice with IR (induced by high-fat diet?+?low-dose streptozotocin). The animals of the study involved the measurements of fasting blood glucose, oral-glucose-tolerance-test, as well as fasting plasma insulin. Moreover, insulin-resistant and insulin-sensitive muscle C2C12 cells were prepared. The insulin-resistance was confirmed by the glucose-uptake assay. Comparative quantitative real time PCR was used to assess the SNCA expression. Results:The obtained results have showed a significant?~?27% decrease in SNCA expression level in muscle tissue of diabetic mice (P?=?0.022). Moreover, there was a significant change of SNCA expression in insulin-resistant C2C12 cells (P?

SUBMITTER: Khoshi A

PROVIDER: S-EPMC6889442 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle.

Khoshi Amirhosein A Goodarzi Golnaz G Mohammadi Rezvan R Arezumand Roghaye R Moghbeli Meysam M Najariyan Mahnaz M

Diabetology & metabolic syndrome 20191202

<h4>Background</h4>Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice.<h4>Materials and methods</h4>Sixteen male C ...[more]

PMID: 31827624

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Project description:Diabetic 'lipotoxicity' theory suggests that fat-induced skeletal muscle insulin resistance (FISMIR) in obesity induced by a high-fat diet (HFD), which leads to ectopic lipid accumulation in insulin-sensitive tissues, may play a pivotal role in the pathogenesis of type 2 diabetes. However, the changes in gene expression and the molecular mechanisms associated with the pathogenesis of FISMIR have not yet been fully elucidated. In the present study the changes in skeletal muscle gene expression were examined in FISMIR in obese insulin-resistant and diabetic hamster models induced by HFD with or without low-dose streptozotocin-treatment. Microarray technology and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to explore the potential underlying molecular mechanisms. The pathophysiological and metabolic features of obesity and type 2 diabetes in humans are closely resembled by these hamster models. The results of microarray analysis showed that the differentially expressed genes associated with metabolism were mostly related to the abnormal regulation and changes in the gene expression of liver X receptor (LXR), peroxisome proliferator-activated receptor (PPAR) and sterol regulatory element-binding protein (SREBP) transcriptional programs in the skeletal muscle from insulin-resistant and diabetic hamsters. The microarray findings confirmed by RT-qPCR indicated that the increased expression of SREBPs and LXRβ and the decreased expression of LXRα and PPARs were involved in the molecular mechanisms of FISMIR pathogenesis in insulin-resistant and diabetic hamsters. A significant difference in the abnormal expression of skeletal muscle LXRs, PPARs and SREBPs was found between insulin-resistant and diabetic hamsters. It may be concluded that the combined abnormal expression of LXR, PPAR and SREBP transcriptional programs may contribute to the development of FISMIR mediated by skeletal muscle lipid accumulation resulting from abnormal skeletal muscle glucose and lipid metabolism in these HFD- and streptozotocin injection-induced insulin-resistant and diabetic hamsters.

Project description:The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, such as resistance exercise (RE), might provide insight to the contributors of sexual dimorphism of muscle phenotypes. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4 h post-exercise) or late recovery (24 h post-exercise) time point. Muscle transcription profiles were compared in the resting state between men (n = 6) and women (n = 8), and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4 h post-exercise, n = 3 males, n = 4 females; 24 h post-exercise, n = 3 males, n = 4 females). A logistic regression-based method (LRpath), following Bayesian moderated t-statistic (IMBT), was used to test gene functional groups and biological pathways enriched with differentially expressed genes.This investigation identified extensive sex differences present in the muscle transcriptome at baseline and following acute RE. In the resting state, female muscle had a greater transcript abundance of genes involved in fatty acid oxidation and gene transcription/translation processes. After strenuous RE at the same relative intensity, the time course of the transcriptional modulation was sex-dependent. Males experienced prolonged changes while females exhibited a rapid restoration. Most of the biological processes involved in the RE-induced transcriptional regulation were observed in both males and females, but sex specificity was suggested for several signaling pathways including activation of notch signaling and TGF-beta signaling in females. Sex differences in skeletal muscle transcriptional regulation might implicate a mechanism behind disproportional muscle growth in males as compared with female counterparts after RE training at the same relative intensity.Sex differences exist in skeletal muscle gene transcription both at rest and following acute RE, suggesting that sex is a significant modifier of the transcriptional regulation in skeletal muscle. The findings from the present study provide insight into the molecular mechanisms for sex differences in muscle phenotypes and for muscle transcriptional regulation associated with training adaptations to resistance exercise.

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Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle.

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Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle.

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