项目来源

德国科学基金(DFG)

项目主持人

Mario Ost

项目受资助机构

未公开

项目编号

506215937

立项年度

2022

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

未知

学科

Nutritional Sciences

学科代码

未公开

基金类别

Research Grants

关键词

未公开

参与者

未公开

参与机构

未公开

项目标书摘要：Metabolic disorders such as obesity are linked to an impaired skeletal muscle homeostasis and a decreased muscle insulin action,one of the earliest metabolic abnormality preceding type 2 diabetes onset,contributing to the etiology of obesity and the decline in metabolic health.Within the present proposal,I aim at testing the hypothesis that a muscle-specific polyamine metabolism is crucial for regulation of muscle metabolism and integrity,with particular focus on spermidine as the most abundant polyamine in a majority of different tissues,that upon supplementation induces autophagy processes.By following both(1)a basic scientific genetic and(2)a polyamine-targeted therapeutic approach,I will address how the muscle-specific spermidine action is coupled to glucose homeostasis and insulin sensitivity,mitochondrial integrity and redox signaling,autophagy mechanisms as well as endocrine muscle crosstalk.Further,I aim to understand how this connection is modified by nutritional stress under obesogenic conditions.The experimental set-up for a comprehensive metabolic and molecular profiling will involve in vivo mouse experiments and synergistic nutritional intervention studies,complemented by ex vivo investigations on intact mouse muscle fibers.Ultimately,this will shed new light on the importance of polyamine action in a tissue-specific as well as endocrine manner,and help to identify strategic target tissues of spermidine treatment to combat obesity-related metabolic dysfunctions.

Application Abstract: Metabolic disorders such as obesity are linked to an impaired skeletal muscle homeostasis and a decreased muscle insulin action,one of the earliest metabolic abnormality preceding type 2 diabetes onset,contributing to the etiology of obesity and the decline in metabolic health.Within the present proposal,I aim at testing the hypothesis that a muscle-specific polyamine metabolism is crucial for regulation of muscle metabolism and integrity,with particular focus on spermidine as the most abundant polyamine in a majority of different tissues,that upon supplementation induces autophagy processes.By following both(1)a basic scientific genetic and(2)a polyamine-targeted therapeutic approach,I will address how the muscle-specific spermidine action is coupled to glucose homeostasis and insulin sensitivity,mitochondrial integrity and redox signaling,autophagy mechanisms as well as endocrine muscle crosstalk.Further,I aim to understand how this connection is modified by nutritional stress under obesogenic conditions.The experimental set-up for a comprehensive metabolic and molecular profiling will involve in vivo mouse experiments and synergistic nutritional intervention studies,complemented by ex vivo investigations on intact mouse muscle fibers.Ultimately,this will shed new light on the importance of polyamine action in a tissue-specific as well as endocrine manner,and help to identify strategic target tissues of spermidine treatment to combat obesity-related metabolic dysfunctions.