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Diets that elevate ketone bodies increase mitochondrial biogenesis and uncoupling protein 1 in brown adipose tissue of mice

Wednesday, October 26, 2011 — Poster Session III

10:00 a.m. – Noon

Natcher Conference Center

NIAAA

ENDOC-10

* FARE Award Winner

Authors

  • S Srivastava
  • Y Kashiwaya
  • R Pawlosky
  • MT King
  • G Niu
  • X Chen
  • K Clarke
  • RL Veech

Abstract

Activating brown adipose tissue (BAT) has been suggested as a treatment to combat obesity. We compared the effects of two different ketone-elevating diets- (i) a commercially available ketogenic diet (KG) and (ii) a liquid diet containing D-b-hydroxybutyrate - R 1,3 butanediol monoester (ketone ester, KE) on activation of BAT in C57BL/6J mice. Feeding the KG and KE diets for one month caused a significant increase in mitochondrial electron transport chain (ETC) proteins, uncoupling protein 1 (UCP1), PPARg, PGC-1a and Sirt1 in the interscapular brown adipose tissue (IBAT). The IBATs from mice on KG and KE diets had elevated cAMP and CREB levels, suggesting activation of sympathetic nervous system. KE diet significantly increased, while KG diet significantly reduced, 18F-fluorodeoxyglucose (FDG) uptake in IBAT measured by positron emission tomography (PET) imaging and measurement of radioactivity. Additionally, the KG group, but not the KE group, had borderline significantly greater body weight-normalized epididymal fat pads. Mice on both KG and KE diet had reduced blood glucose, but only KE group had higher plasma leptin levels compared to corresponding controls. These results indicate that the KE diet is a better alternative to the KG diet for activating BAT to combat obesity and the metabolic syndrome.

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