Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet.
Level 5 - mechanism / opinion, no new human data
Animal research with no human data
PubMed 22362892 · doi:10.1096/fj.11-200410
What was done
Eight-week-old male C57BL/6J mice were fed for up to 1 month with a diet where D-β-hydroxybutyrate-(R)-1,3 butanediol monoester (ketone ester, KE) replaced equicaloric amounts of carbohydrate, with equal fat, protein, and micronutrients. The KE group was fed ad libitum, and control mice were pair-fed to the KE group. Authors evaluated blood D-β-hydroxybutyrate levels, food intake, interscapular brown adipose tissue (IBAT) mitochondrial markers, [(18)F]-fluorodeoxyglucose uptake, plasma leptin, resting and 24-hour energy expenditure, body weight, and insulin sensitivity.
What was found
Blood D-β-hydroxybutyrate in the KE group was 3–5 times higher than reported with high-fat ketogenic diets, and voluntary food intake decreased dose-dependently. IBAT showed doubled electron transport chain proteins, uncoupling protein 1 (UCP1), mitochondrial biogenesis-regulating proteins, and [(18)F]-fluorodeoxyglucose uptake. Plasma leptin increased over 2-fold with elevated sympathetic nervous system activity to IBAT. Resting energy expenditure increased by 14% and the quantitative insulin-sensitivity check index rose by 73%. Total 24-hour energy expenditure and body weight showed no significant difference between groups.
Why it matters
This study shows that oral ketone ester supplementation can stimulate brown fat thermogenic machinery, increase resting metabolic rate, and improve insulin sensitivity markers in a rodent model.
Limits
The study was conducted exclusively in young male mice, precluding direct clinical conclusions in humans. The abstract does not state the sample size (n). Despite the 14% rise in resting metabolic rate, total 24-hour energy expenditure and body weight were unaffected.
Cited by
- partial Shifting toward oxidative phosphorylation and ketone metabolism forces cells to upregulate mitochondrial biogenesis and electron transport chain proteins.