Metabolism as a tool for understanding XXXX brain evolution: Lipid energy metabolism as an example.

@entity1 @entity28 @entity1674 @entity13513 @entity6178 @entity2453 @entity1718
Genes and the environment both influence the metabolic processes that determine fitness. To illustrate the importance of metabolism for @entity1 brain evolution and health, we use the example of lipid energy metabolism, i.e. the use of fat (lipid) to produce energy and the advantages that this metabolic pathway provides for the brain during environmental energy shortage. We briefly describe some features of metabolism in ancestral organisms, which provided a molecular toolkit for later development. In modern @entity1 , lipid energy metabolism is a regulated multi-organ pathway that links @entity1674 in fat tissue to the mitochondria of many tissues including the brain. Three important control points are each suppressed by insulin. (1) Lipid reserves in adipose tissue are released by lipolysis during fasting and stress, producing @entity1718 (FAs) which circulate in the blood and are taken up by cells. (2) FA oxidation. Mitochondrial entry is controlled by @entity13513 ( @entity13513 ). Inside the mitochondria, FAs undergo beta oxidation and energy production in the Krebs cycle and respiratory chain. (3) In liver mitochondria, the @entity2453 ( @entity2453 ) pathway produces @entity6178 bodies for the brain and other organs. Unlike most tissues, the brain does not capture and metabolize circulating FAs for energy production. However, the brain can use @entity6178 bodies for energy. We discuss two examples of genetic metabolic traits that may be advantageous under most conditions but deleterious in others. (1) A @entity13513 variant prevalent in Inuit @entity1 may allow increased FA oxidation under nonfasting conditions but also predispose to hypoglycemic episodes. (2) The thrifty genotype theory, which holds that energy expenditure is efficient so as to maximize energy stores, predicts that these adaptations may enhance survival in periods of famine but predispose to @entity28 in modern dietary environments.
