The central benefit of physiologically induced ketogenic states.

Ketones not only act as metabolic fuel for the brain in periods of carbohydrate shortage, but also serve as signalling molecules that improve cognition. Ketogenic states can be induced peripherally by physiological interventions such as fasting and exercise, or ketogenic diets/exogenous supplementation. These interventions beneficially act on the brain through partially overlapping peripheral metabolic pathways. We focus on the role of peripheral organs such as the intestine, liver and skeletal muscle in mediating cognitive benefits in response to these interventions and discuss the prominent roles of the nuclear receptor peroxisome proliferator-activated receptor δ, which serves as a nutrient sensor guiding ketones to the brain, where they stimulate the multifunctional cognition-improving factor, brain-derived neurotrophic factor.