# Threonic acid, an ascorbic acid metabolite, synergizes with intermittent fasting to ameliorate obesity

## TL;DR

Combining intermittent fasting with threonic acid, a vitamin C metabolite, improves obesity treatment in mice by reducing weight and boosting metabolism.

## Contribution

Threonic acid synergizes with intermittent fasting to enhance obesity treatment through hypothalamic regulation of appetite-related neuropeptides.

## Key findings

- Combining intermittent fasting with threonic acid reduced body weight and food intake more effectively than either treatment alone.
- Threonic acid suppressed hypothalamic orexigenic neuropeptides NPY and AGRP during fasting.
- Threonic acid competed with glucose for uptake via GLUT3, enhancing its metabolic effects during fasting.

## Abstract

Intermittent fasting (IF) is a safe and sustainable approach for obesity treatment, yet its weight loss efficacy is relatively modest compared with that of pharmacologic anti-obesity therapies. The synergistic benefits of pairing IF with administration of nutrient-derived metabolites remain poorly understood. Here we report that combining IF with threonic acid (TA), an ascorbic acid metabolite, led to more pronounced reductions in body weight and food intake, as well as improvements in energy expenditure and glycemic control, compared with either intervention alone in diet-induced obese mice. These metabolic benefits were associated with the anorexigenic role of TA in reversing fasting-induced upregulation of the hypothalamic orexigenic neuropeptides NPY and AGRP. In the hypothalamus, TA competed with glucose for uptake via glucose transporter 3 (GLUT3), while IF boosted the TA uptake through both glucose depletion and upregulation of GLUT3, resulting in a more robust suppression of NPY and AGRP expression. Collectively, our findings highlight the combination of TA with IF as a promising metabolite-based combinatorial strategy to enhance the therapeutic efficacy of obesity treatment.

Obesity is a growing health issue worldwide. Current treatments have side effects and limited long-term success. This study explores combining intermittent fasting (IF), a dietary approach involving alternating periods of eating and fasting, with either ascorbic acid (AA, also known as vitamin C) or its metabolite, threonic acid (TA), to enhance obesity treatment. In the study, mice were fed a high-fat diet to induce obesity and then subjected to IF and AA or TA treatments. Researchers found that IF combined with TA was more effective than IF with AA or either treatment alone in reducing body weight and improving metabolic health. These metabolic benefits were associated with TA’s appetite-suppressing action in reversing fasting-induced increases in hypothalamic orexigenic neuropeptides. The study concludes that TA could be a promising strategy for treating obesity.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.