Mitochondrial Biogenesis and Increased Uncoupling Protein 1 in Brown Adipose Tissue of Mice Fed a Ketone Ester Diet

Abstract

We investigated the in vivo physiological responses to a diet in which D‐β‐hydroxybutyrate – (R)‐1,3 butanediol monoester (ketone ester, KE) replaced equicaloric amounts of carbohydrate in eight week old male C57BL/6J. The KE‐fed group had blood D‐β‐hydroxybutyrate (β HB) levels that were much greater than that achieved with high fat ketogenic diets. Voluntary food intake reduced dose‐dependently with KE in the diet. Feeding the KE diet for a month significantly increased the number of mitochondria, uncoupling protein 1 (UCP1), PPARγ, PGC‐1α as well as Sirt1 in the interscapular brown adipose tissue (IBAT). The KE group also had significantly greater 18F‐fluorodeoxyglucose (FDG) uptake in IBAT, indicating functional activation of the tissue. The ketone fed mice had greater plasma leptin levels and increased sympathetic nervous system activity to IBAT. KE‐fed mice exhibited elevated resting energy expenditure, but no difference in the total energy expenditure or body weight. The quantitative insulin‐sensitivity check index (QUICKI) was also significantly greater in the KE group. These results demonstrate KE as a potential anti‐obesity supplement.