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Metabolic and transcriptional adaptations improve physical performance of zebrafish

ABSTRACT: Metabolic and transcriptional adaptations improve physical performance of zebrafish

PROVIDER: PRJNA758884 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15667940.fastq.gz	Fastqsanger.gz
	SRR15667941.fastq.gz	Fastqsanger.gz
	SRR15667942.fastq.gz	Fastqsanger.gz
	SRR15667943.fastq.gz	Fastqsanger.gz
	SRR15667944.fastq.gz	Fastqsanger.gz

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Metabolic and transcriptional adaptations improve physical performance of zebrafish

Project description:Background: Obesity is a worldwide public health problem with increasing prevalence and affects 80% of diabetes mellitus type 2 cases. Zebrafish (Danio rerio) are an established model organism for studying obesity and diabetes including diabetic microvascular complications. We aimed to determine whether physical activity is an appropriate tool to examine training effects in zebrafish and to analyse metabolic and transcriptional processes in trained zebrafish. Methods: A 2- and 8-weeks experimental training phase protocol with adult zebrafish in a swim tunnel system was established. We examined zebrafish basic characteristics before and after training such as body weight, body length and maximum speed and considered overfeeding as an additional parameter in the 8-weeks training protocol. Ultimately, the effects of training and overfeeding on blood glucose, muscle core metabolism and liver gene expression using RNA-Seq were investigated. Results: Zebrafish maximum speed was correlated with body length and was significantly increased after 2 weeks of training. Maximum swim speed further increased after 8 weeks of training in both the normalfed and the overfed groups, but training was found not to be sufficient in preventing weight gain in overfed fish. Metabolome and transcriptome profiling in trained fish exhibited increased blood glucose levels in the short-term and upregulated energy supply pathways in the long-term. Conclusion: Swim training is a valuable tool to study effects of physical activity in zebrafish, which is accompanied by metabolic and transcriptional adaptations.

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Muscle cannabinoid 1 receptor regulates Il-6 and myostatin expression, governing physical performance and whole-body metabolism.

Project description:Cannabinoid 1 receptor (CB1R) plays a critical role in the regulation of whole-body energy metabolism because of its involvement in controlling food intake thorough a central mechanism, and controlling distribution of fuel and utilization in the periphery, particularly in fat and liver. Additionally, inhibition of CB1R improves insulin secretion from pancreatic beta cells and insulin sensitivity in both pancreatic beta cells and hepatocytes. We now developed a skeletal muscle-specific CB1R-knockout (Skm-CB1R-/-) mouse to study the specific role of CB1R in muscle. Muscle-CB1R ablation prevented diet-induced and age-induced insulin resistance by increasing insulin receptor signaling. Ablation of CB1R in muscle also led to IL-6 secretion and reduced myostatin expression, and enhanced AKT and MAPKs signaling. These changes in myokines induced the expression of myogenic genes, increasing muscle mass and whole-body lean/fat ratio in both obesity and aging, with no change in total body weight. Skm-CB1R-/- mice had increased energy expenditure and their muscle had improved mitochondrial performance, which led to improved physical endurance. These results collectively show that muscle-CB1R is involved in regulating whole-body insulin sensitivity and physical performance.

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