The AMPK-malonyl-CoA-CPT1 axis in the control of hypothalamic neuronal function
Zammit, Victor A. and Arduini, Arduino (2008) The AMPK-malonyl-CoA-CPT1 axis in the control of hypothalamic neuronal function. Cell Metabolism, Vol.8 (No.3). p. 175. ISSN 1550-4131Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.cmet.2008.07.009
We would like to offer alternative perspectives to those suggested in a recent article in Cell Metabolism on the potential roles of FAS, malonyl-CoA and CPT1 in hypothalamic function. In Lopez et al., 2008 the fasting- and ghrelin-mediated (AMPK-dependent) downregulation of FAS expression was proposed to be “an adaptive mechanism that helps to prevent malonyl-CoA from decreasing to deleteriously low levels in the hypothalamus.” We suggest that the downregulation of FAS serves to prime neurons to respond to refeeding by enabling a more rapid increase in [malonyl-CoA] when feeding signals reach the hypothalamus; this would control meal size more efficiently. The rationale for a CPT1C-associated signaling role for malonyl-CoA independently from its inhibition of CPT1 activity is not supported by existing data. CPT1C (the activity of which is difficult to detect in vitro even with the use of sensitive radiochemical assays, owing to its extremely low catalytic constant [Sierra et al., 2008]) binds malonyl-CoA with the same affinity as CPT1A (Price et al., 2002). We have suggested that it could buffer the availability of malonyl-CoA in specific microenvironments within the cell (Price et al., 2002). Malonyl-CoA is capable of signaling indirectly through its inhibition of the highly active isoforms CPT 1A and/or 1B; such inhibition raises the concentrations of cytosolic long-chain acyl-CoA (LC-CoA) esters, potentially making CPT 1 activity central to neuroendocrine cell responses, as these metabolites are (1) activators of the K+ATP channels and therefore able to affect neuronal electrical activity, and (2) sensitizers of vesicular (neuro)peptide secretion.
|Item Type:||Journal Item|
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Cell Metabolism|
|Official Date:||3 September 2008|
|Page Range:||p. 175|
|Access rights to Published version:||Restricted or Subscription Access|
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