Therapeutic Efficacy of β-Hydroxybutyrate Supplementation on Weight Loss and Glycemic Control in Fasted Obese and Diabetic Mice

Abstract

The global prevalence of obesity and diabetes necessitates novel therapeutic interventions. Ketone bodies, particularly beta-hydroxybutyrate (BHB), have emerged as promising agents for metabolic management. This study assessed how effective the efficacy of oral beta-hydroxybutyrate (BHB) supplementation on weight loss and glycemic control in a streptozotocin (STZ; 50 mg/kg, intraperitoneal) mouse model of obesity and diabetes induced by a high-fat diet (HFD, which consists of 45% beef tallow, 35% egg yolk, and 20% commercial food pellets) for 21 days under a 16-hour daily fasting protocol.  Male Swiss Webster mice were divided into four groups and orally administered: metformin (0.1 mg/g) (positive control), low-dose BHB (3.75 mg/g), high-dose BHB (7.5 mg/g), and water (negative control). All treatments were administered once daily for 14 days. At the end of the treatment period, parameters evaluated included final body weight, fasting blood glucose (FBG) levels in the tail vein on days 0, 1, 7, and 14, and urinary ketone levels via urine sampling. Results demonstrated that high-dose BHB administration induced a significantly reduced body weight (p < 0.05) and fasting blood glucose levels (p < 0.01), with efficacy comparable to that of metformin. The low-dose BHB group showed a statistically significant improvement in fasting blood glucose (FBG) (p < 0.05) but did not significantly reduce body weight. Critically, urinary ketones remained undetectable, indicating no induction of ketoacidosis. These results suggest that oral BHB supplementation, particularly at higher doses, is a safe and effective strategy for improving metabolic outcomes during fasting in obese and diabetic models, positioning it as a viable adjunct therapeutic option.