The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility

Zhang, Shuai; Hulver, Matthew W.; McMillan, Ryan P.; Cline, Mark A.; Gilbert, Elizabeth R.

The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility

dc.contributor.author	Zhang, Shuai	en
dc.contributor.author	Hulver, Matthew W.	en
dc.contributor.author	McMillan, Ryan P.	en
dc.contributor.author	Cline, Mark A.	en
dc.contributor.author	Gilbert, Elizabeth R.	en
dc.contributor.department	Animal and Poultry Sciences	en
dc.date.accessioned	2014-02-15T16:01:09Z	en
dc.date.available	2014-02-15T16:01:09Z	en
dc.date.issued	2014-02-12	en
dc.date.updated	2014-02-15T16:01:09Z	en
dc.description.abstract	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).	en
dc.description.version	Published version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Nutrition & Metabolism. 2014 Feb 12;11(1):10	en
dc.identifier.doi	https://doi.org/10.1186/1743-7075-11-10	en
dc.identifier.uri	http://hdl.handle.net/10919/25431	en
dc.language.iso	en	en
dc.rights	Creative Commons Attribution 4.0 International	en
dc.rights.holder	Shuai Zhang et al.; licensee BioMed Central Ltd.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.title	The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility	en
dc.title.serial	Nutrition & Metabolism	en
dc.type	Article - Refereed	en
dc.type.dcmitype	Text	en