Advisory Committee Chair
Eric P Plaisance
Advisory Committee Members
Daniel L Smith JR
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Health Professions
Objective: Exogenous ketone administration presents a possible treatment strategy for obesity and obesity-related diseases. The exogenous ketone ester, R,S-1,3-butanediol diacetoacetate (BD-AcAc2) decreases adiposity and hepatic steatosis in high-fat dietinduced obese mice. In our previous work, carbohydrate energy was removed and replaced with the ketone ester to produce isocaloric diets. The current investigation aimed to determine whether BD-AcAc2 decreases markers of hepatic steatosis and inflammation in lean mice on a high-fat, high-sugar (HFHS) diet without removing carbohydrate energy. Methods: Sixteen 11-week-old male C57BL/6J mice were randomized to one of two groups for 9 weeks (n = 8 per group): 1) Control (CON, HFHS diet) or 2) Ketone ester (KE, HFHS diet + BD-AcAc2, 25% by kcals). Results: Body weight increased by 56% in CON (27.8 ± 2.5 to 43.4 ± 3.7 g, p < 0.001) and by 13% in KE (28.0 ± 0.8 to 31.7 ± 3.1 g, p = 0.001). The CON group had a greater accretion of total adiposity compared to the KE group (p < 0.001). Despite significant differences in body weight and adiposity, energy intake and expenditure were similar between groups. Nonalcoholic fatty liver disease activity scores for hepatic steatosis, inflammation, and ballooning were lower in the KE group compared to CON (p < 0.001 for all). Markers of hepatic inflammation [Tnfα (p = 0.036); Mcp1 (p < 0.001)], macrophage content [(Cd68 (p = 0.012)], and collagen deposition and hepatic stellate cell activation [(αSma (p = 0.004); Col1A1 (p < 0.001)] were significantly lower in the KE group compared to CON. Conclusions: BDiv AcAc2 administration abolishes HFHS-induced markers of liver steatosis, inflammation, ballooning, and fibrosis in lean B6 mice. Future studies should explore the physiological and molecular mechanisms responsible for these findings.
Rushing, Kelsey A., "Effects of Dietary R, S-1, 3-Butanediol Diacetoacetate on Components of Energy Balance and Hepatic Health" (2023). All ETDs from UAB. 384.