title: Ketones suppress brain glucose consumption.
abstract: The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as beta-hydroxybutyrate (beta HB) and acetoacetate (AcAc), as occurs with fasting, prolonged starvation or chronic feeding of a high fat/low carbohydrate diet (ketogenic diet). In this study, the local cerebral metabolic rate of glucose consumption (CMRglu; microM/min/100g) was calculated in the cortex and cerebellum of control and ketotic rats using Patlak analysis. Rats were imaged on a rodent PET scanner and MRI was performed on a 7-Tesla Bruker scanner for registration with the PET images. Plasma glucose and beta HB concentrations were measured and 90-minute dynamic PET scans were started simultaneously with bolus injection of 2-Deoxy-2[18F]Fluoro-D-Glucose (FDG). The blood radioactivity concentration was automatically sampled from the tail vein for 3 min following injection and manual periodic blood samples were taken. The calculated local CMRGlu decreased with increasing plasma BHB concentration in the cerebellum (CMRGlu = -4.07*[BHB] + 61.4, r2 = 0.3) and in the frontal cortex (CMRGlu = -3.93*[BHB] + 42.7, r2 = 0.5). These data indicate that, under conditions of ketosis, glucose consumption is decreased in the cortex and cerebellum by about 10% per each mM of plasma ketone bodies.
authors.affiliation: Department of Anatomy, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: LaManna
authors.forename: Nicolas
authors.initials: N
authors.lastname: Salem
authors.forename: Michelle
authors.initials: M
authors.lastname: Puchowicz
authors.forename: Bernadette
authors.initials: B
authors.lastname: Erokwu
authors.forename: Smruta
authors.initials: S
authors.lastname: Koppaka
authors.forename: Chris
authors.initials: C
authors.lastname: Flask
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007659:Ketones; D005947:Glucose