The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility

Nutrition & Metabolism

Elizabeth R Gilbert³  Mark A Cline¹  Ryan P McMillan²  Matthew W Hulver²  Shuai Zhang¹ 

[1] Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA USA;Department of Human Nutrition, Foods and Exercise and Metabolic Phenotyping Core, Virginia Tech, Blacksburg, VA USA;3200 Litton-Reaves, Animal & Poultry Sciences Department, Virginia Tech, Blacksburg, VA 24061-0306, USA

关键词: Metabolic flexibility;    PDK;    PDC;   

Others  :  802749
DOI  :  10.1186/1743-7075-11-10

 received in 2013-12-17, accepted in 2014-02-08,  发布年份 2014

【 摘 要 】

Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. The ability to alter substrate oxidation in response to nutritional state depends on the genetically influenced balance between oxidation and storage capacities. Competition between fatty acids and glucose for oxidation occurs at the level of the pyruvate dehydrogenase complex (PDC). The PDC is normally active in most tissues in the fed state, and suppressing PDC activity by pyruvate dehydrogenase (PDH) kinase (PDK) is crucial to maintain energy homeostasis under some extreme nutritional conditions in mammals. Conversely, inappropriate suppression of PDC activity might promote the development of metabolic diseases. This review summarizes PDKs’ pivotal role in control of metabolic flexibility under various nutrient conditions and in different tissues, with emphasis on the best characterized PDK4. Understanding the regulation of PDC and PDKs and their roles in energy homeostasis could be beneficial to alleviate metabolic inflexibility and to provide possible therapies for metabolic diseases, including type 2 diabetes (T2D).

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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