The dietary R ‐3‐hydroxybutyrate‐ R ‐1,3‐butanediol monoester increases resting energy expenditure (REE) and markers of brown and white adipose thermogenesis in lean mice. The purpose of this investigation was to determine whether the ketone ester, R,S ‐1,3‐butanediol diacetoacetate (BD‐AcAc ₂ ), increases energy expenditure and markers of adipose tissue thermogenesis in the context of high‐fat diet (HFD)‐induced obesity. Thirty‐five‐week‐old male C57BL/ 6J mice were placed on an ad libitum HFD (45% kcal) for 10 wk. The mice were then randomized to 1 of 3 groups (n = 10 per group) for an additional 12 wk: 1 ) control (Con), continuous HFD, 2) pair‐fed (PF) to ketone ester (KE); and 3) KE: HFD +30% energy from BD‐AcAc ₂ . Mean energy intake throughout the study was ∼26% lower in the KE compared to the Con group (8.2 ± 0.5 vs . 11.2 ± 0.7 kcal/d; P < 0.05). Final body weight (26.8 ± 3.6 vs . 34.9 ± 4.8 g; P < 0.001) and fat mass (5.2 ± 1.2 vs . 11.3 ± 4.5 g; P < 0.001) of the KE group was significantly lower than PF, despite being matched for energy provisions. Differences in body weight and adiposity were accompanied by higher REE and total energy expenditure in the KE group compared to PF after adjustment for lean body mass and fat‐mass ( P = 0.001 and 0.007, respectively). Coupled or uncoupled mitochondrial respiratory rates in skeletal muscle were not different among groups, but markers of mitochondrial uncoupling and thermogenesis (uncoupling protein‐1, deiodinase‐2, and peroxisome proliferator‐activated receptor y coactivator‐1α) were higher in interscapular brown adipose tissue (BAT) of mice receiving the KE diet. The absence of mitochondrial uncoupling in skeletal muscle and increased markers of mitochondrial uncoupling in BAT suggest that BD‐AcAc ₂ initiates a transcriptional signature consistent with BAT thermogenesis in the context of HFD‐induced obesity.—Davis, R. A. H., Deemer, S. E., Bergeron, J. M., Little, J. T., Warren, J. L., Fisher, G., Smith, D. L., Jr., Fontaine, K. R., Dickinson, S. L., Allison, D. B., Plaisance, E. P. Dietary R,S‐1,3‐butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high‐fat diet. FASEB J. 33, 2409–2421 (2019). www.fasebj.org

Objectives: Exogenous ketones may provide therapeutic benefit in treatment of obesity. Administration of the ketone ester (KE) R,S-1,3-butanediol acetoacetate diester (BD-AcAc₂) decreases body weight in mice, but effects on energy balance have not been extensively characterized. The purpose of this investigation was to explore concentration-dependent effects of BD-AcAc₂ on energy intake and expenditure in mice. Methods: Forty-two male C57BL/6J mice were randomly assigned to one of seven isocaloric diets (n = 6 per group): (1) Control (CON, 0% KE by kcals); (2) KE5 (5% KE); (3) KE10 (10% KE); (4) KE15 (15% KE); (5) KE20 (20% KE); (6) KE25 (25% KE); and (7) KE30 (30% KE) for 3 weeks. Energy intake and body weight were measured daily. Fat mass (FM), lean body mass (LBM), and energy expenditure (EE) were measured at completion of the study. Differences among groups were compared to CON using ANOVA and ANCOVA. Results: Mean energy intake was similar between CON and each concentration of KE, except KE30 which was 12% lower than CON (P < 0.01). KE25 and KE30 had lower body weight and FM compared to CON, while only KE30 had lower LBM (P < 0.03). Adjusted resting and total EE were lower in KE30 compared to CON (P < 0.03), but similar for all other groups. Conclusions: A diet comprised of 30% energy from BD-AcAc₂ results in lower energy intake, coincident with lower body weight and whole animal adiposity; while KE20 and KE25 have significantly lower body weight and adiposity effects independent of changes in energy intake or expenditure.

Objective. The purpose of this study was to examine the relationship between fasting serum leptin and adiponectin levels with bone mineral density (BMD) and body composition in pre-menopausal, middle-aged Hispanic and Caucasian women. Objective. Participants' (68 Hispanic and 36 Caucasian) BMD and bone mineral content were measured by dual-energy X-ray absorptiometry, and body density was measured by hydrodensitometry. Serum leptin was determined by enzyme immunoassay and adiponectin by ELISA. Results. Hispanic women had significantly higher leptin, BMD, and fat mass (FM), and lower adiponectin than Caucasian women. There was no significant correlation between leptin and BMD for Hispanic or Caucasian women; adiponectin was inversely correlated with BMD in Caucasian women only (p = 0.01). In both Hispanic and Caucasian women, lean body mass and adiponectin best explained the variance in BMD (r² = 0.25, p < 0.001). Conclusion. These data demonstrate no significant relationship between leptin and BMD of pre-menopausal, middle-aged Hispanic and Caucasian women, and a significant inverse relationship between adiponectin and BMD in Caucasian women. The role of adipocytokines in the regulation of BMD remains inconclusive and may vary across ethnic groups.