Publication Highlight: The Synergistic Power of Intermittent Fasting and Threonic Acid in DIO Mice
This publication highlight reviews how intermittent fasting and threonic acid affected body weight, fat mass, lean mass, and metabolic outcomes in diet-induced obese mice, with iNSiGHT DXA used for body composition analysis.
Authors
Oh, S.; Park, S.; Kim, E.-K.
Overview
Obesity is a major public health concern, yet many pharmacological solutions show challenges with maintaining long-term benefits and can even lead to significant side effects. Intermittent fasting (IF) is a safe alternative, but its weight loss efficacy is modest. Ascorbic acid (AA), also known as vitamin C, has been identified for its anti-obesity effects. However, its therapeutic use has been limited by its instability and rapid metabolism into various compounds, including threonic acid (TA).
A new study by Oh et al., 2025 aimed to investigate the anti-obesity effects of combining IF with AA or its metabolite, TA, using a diet-induced obese (DIO) mouse model.
Study Design
To do this, they used male and female C57BL/6N mice fed a high fat diet (HFD) for 16 weeks. Thereafter, daily i.p. injections of either a vehicle, AA (up to 15 mmol/kg), or TA (1.5 mmol/kg) were performed for 50 days concurrent to either ad libitum feeding or alternate-day fasting. Importantly, the iNSiGHT DXA system was used to analyze body composition (lean and fat mass), indirect calorimetry was employed to measure energy expenditure, and LC-MS/MS provided data about AA metabolism in the brain.
What They Found Was Truly Remarkable
Adapted from Fig. 1 (PMID: 41507308). Combining AA with IF enhances anti-obesity effects in DIO mice. D) Representative images of body composition. Red, fat mass; green, lean mass. E) Fat mass (left) and lean mass (right) on day 50 (n = 6).
- When IF and TA administration were combined, DIO mice demonstrated a significant reduction in body weight (23.7%) compared to either intervention alone, suggesting a synergistic effect.
- TA was identified as the metabolite responsible for suppressing orexigenic neuropeptides (NPY and AGRP), leading to reduced hunger signals during fasting.
- IF led to glucose depletion and an upregulation of GLUT3 transporter; collectively, more TA was able to enter neurons since it could bind to GLUT3 with less competition by glucose.
- The combination therapy significantly improved glucose tolerance, insulin sensitivity, and energy expenditure while increasing thermogenesis in brown adipose tissue.
Study Conclusion
This led the authors to conclude that when combined, TA and IF appear to synergistically support weight loss and improve markers of insulin sensitivity. Taken together, these strategies may enhance the efficacy of obesity treatments.
iNSiGHT DXA in This Research
Scintica is pleased to highlight the iNSiGHT DXA system in this research where it was used to evaluate the body composition of diet-induced obese (DIO) mice following 50 days of treatment. The Insight software enabled:
Key Features
- Fat mass and lean mass measurements in under 30 seconds
- Color maps to visualize the region-specific soft tissue type (green for lean, red for fat – color scheme is customizable!)
- A user-friendly experience
Disclaimer: The DXA system was used for data acquisition, while all statistical analyses and graph creation were performed using GraphPad Prism software.
