Loss of ACOT7 potentiates seizures and metabolic dysfunction.

Loss of ACOT7 potentiates seizures and metabolic dysfunction. Am J Physiol Endocrinol Metab. 2019 Apr 30;: Authors: Bowman CE, Selen Alpergin ES, Ellis JM, Wolfgang MJ Abstract Neurons uniquely antagonize fatty acid utilization by hydrolyzing the activated form of fatty acids, long chain acyl-CoAs, via the enzyme acyl-CoA thioesterase 7, Acot7. The loss of Acot7 results in increased fatty acid utilization in neurons and exaggerated stimulus-evoked behavior. To understand the contribution of Acot7 to seizure susceptibility we generated Acot7 KO mice and assayed their response to kainate-induced seizures. Acot7 KO mice exhibited potentiated behavioral and molecular indices of seizure severity following kainic acid administration suggesting that fatty acid metabolism in neurons can be a critical regulator of neuronal activity. These data are consistent with the presentation of seizures in a human with genomic deletion of ACOT7demonstrating the conservation of function across species. To further understand the metabolic complications arising from a deletion in Acot7, we subjected Acot7 KO mice to a high-fat diet. While the loss of Acot7 did not result in metabolic complications following a normal chow diet, a high-fat diet induced greater body weight gain, adiposity and glucose intolerance in Acot7 KO mice. These data demonstrate that Acot7, a fatty acid metabolic enzyme highly enriched in neurons, regulates both brain-specific metabolic...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research