Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet

FASEB J. 2012 Jun;26(6):2351-62. doi: 10.1096/fj.11-200410. Epub 2012 Feb 23.


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.

MeSH terms

  • 3-Hydroxybutyric Acid / pharmacology
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Diet
  • Eating
  • Electron Transport Chain Complex Proteins / metabolism
  • Fluorodeoxyglucose F18 / metabolism
  • Hydroxybutyrates / pharmacology*
  • Insulin Resistance
  • Ion Channels / biosynthesis*
  • Ketone Bodies / blood
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / biosynthesis*
  • Uncoupling Protein 1


  • Electron Transport Chain Complex Proteins
  • Hydroxybutyrates
  • Ion Channels
  • Ketone Bodies
  • Leptin
  • Mitochondrial Proteins
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • beta-hydroxybutyrate-1,3-butanediol monoester
  • Fluorodeoxyglucose F18
  • 3-Hydroxybutyric Acid