Fuel-sensing mechanisms integrating lipid and carbohydrate utilization.

@article{Sugden2001FuelsensingMI,
  title={Fuel-sensing mechanisms integrating lipid and carbohydrate utilization.},
  author={Mary C. Sugden and Karen Bulmer and Mark J. Holness},
  journal={Biochemical Society transactions},
  year={2001},
  volume={29 Pt 2},
  pages={
          272-8
        }
}
Fuel metabolism is highly regulated to ensure adequate energy for cellular function. The contribution of the major metabolic fuels--glucose, lactate and fatty acids (FAs)--often reflects their circulating levels. In addition, regulatory cross-talk and fuel-induced hormone secretion ensures appropriate and co-ordinate fuel utilization. Because its activity can either determine or reflect fuel preference (carbohydrate versus fat), the pyruvate dehydrogenase complex (PDC) occupies a pivotal… 

Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.

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Recent significant advances in knowledge of the mechanisms regulating PDC are summarized, with emphasis on the PDKs, in particular PDK4, whose expression is linked with sustained changes in tissue lipid handling and which may represent an attractive target for pharmacological interventions aimed at modulating whole body glucose, lipid, and lactate homeostasis in disease states.

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Recent advances relating to the acute and long-term modes of regulation of the PDKs are described, with particular emphasis on the regulatory roles of nuclear receptors, PPAR γ coactivator α (PGC-1α) and insulin, and the impact of changes in PDK activity and expression in glucose and lipid homeostasis.

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The effects of PDK inhibition on the prevention of metabolic diseases using pharmacological inhibitors are described and PDK isoenzymes are strong therapeutic targets for preventing and treating metabolic diseases.

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Pyruvate Dehydrogenase Kinase 4

PDK4 upregulation in adipocytes participates in the hypolipidemic effect of thiazolidinediones through modulation of glyceroneogenesis, therefore altering nonesterified fatty acid release in both basal and rosiglitazone-activated conditions.

[Transcriptional regulation of metabolic switching PDK4 gene under various physiological conditions].

Results suggest that PGC-1alpha plays an essential role not only in regulating the amounts of energy creating enzymes, but also at the step of metabolic switching with unevenly distributed tissue transcription factors such as ERRalpha in the skeletal muscle, thus harmonizing tissue-specific functions and energy metabolism.

Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).

The data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARalpha.

Disturbed bovine mitochondrial lipid metabolism: a review

Assuming that liver carnitine concentrations might limit hepatic fatty acid oxidation capacity in dairy cows, further study of the role of acyl-CoA dehydrogenases and/or riboflavin in bovine ketosis is warranted.
...

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