title: Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet.
abstract: We measured the effects of a diet in which D-β-hydroxybutyrate-(R)-1,3 butanediol monoester [ketone ester (KE)] replaced equicaloric amounts of carbohydrate on 8-wk-old male C57BL/6J mice. Diets contained equal amounts of fat, protein, and micronutrients. The KE group was fed ad libitum, whereas the control (Ctrl) mice were pair-fed to the KE group. Blood d-β-hydroxybutyrate levels in the KE group were 3-5 times those reported with high-fat ketogenic diets. Voluntary food intake was reduced dose dependently with the KE diet. Feeding the KE diet for up to 1 mo increased the number of mitochondria and doubled the electron transport chain proteins, uncoupling protein 1, and mitochondrial biogenesis-regulating proteins in the interscapular brown adipose tissue (IBAT). [(18)F]-Fluorodeoxyglucose uptake in IBAT of the KE group was twice that in IBAT of the Ctrl group. Plasma leptin levels of the KE group were more than 2-fold those of the Ctrl group and were associated with increased sympathetic nervous system activity to IBAT. The KE group exhibited 14% greater resting energy expenditure, but the total energy expenditure measured over a 24-h period or body weights was not different. The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement.
authors.affiliation: Laboratory of Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA.
authors.forename: Shireesh
authors.initials: S
authors.lastname: Srivastava
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kashiwaya
authors.forename: M Todd
authors.initials: MT
authors.lastname: King
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baxa
authors.forename: Joseph
authors.initials: J
authors.lastname: Tam
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.forename: Richard L
authors.initials: RL
authors.lastname: Veech
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D004032:Diet; D004435:Eating; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007333:Insulin Resistance; D007473:Ion Channels / Q000096:biosynthesis*; D007657:Ketone Bodies / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D000071256:Uncoupling Protein 1
chemical_list: D045222:Electron Transport Chain Complex Proteins; D006885:Hydroxybutyrates; D007473:Ion Channels; D007657:Ketone Bodies; D020738:Leptin; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C574168:beta-hydroxybutyrate-1,3-butanediol monoester; D019788:Fluorodeoxyglucose F18; D020155:3-Hydroxybutyric Acid