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Fasting, exercise, calorie restriction, ketogenic diets, and any other state that induces endogenous BHB production will only produce R-type BHB(R-BHB) ( via ACSS2, for example, ACSS2 is thought to be the enzyme that generates crotonyl-CoA from crotonate and butyryl-CoA from butyrate ( Figure 2 Chromatin modifications sensitize the genome to cellular metabolism changes, thereby establishing different functional adaptive states