Succinate, a key compound of energy metabolism, sits at the center of a recent international study published in Acta Physiologica. The analysis, conducted with the collaboration of the Scuola Superiore Sant’Anna in Pisa, the Istituto di Fisiologia Clinica of the CNR in Pisa, the University of Pisa, Scuola Normale Superiore, and the University of California, Irvine (US), highlights the molecule’s capacity to mimic the effects of intermittent fasting – intermittent fasting – with benefits on obesity, including weight loss and related metabolic syndrome, and brain disorders.
It is well known, in fact, the close link between this weight condition and the risk associated with the development of cognitive disorders.
The Evidence
Benefits on metabolism, behavior, and brain inflammation in obese individuals are, in fact, attributable to succinate’s ability to mediate the positive effects of intermittent fasting – intermittent fasting – with benefits on obesity, including weight loss and related metabolic syndrome, and brain disorders.
Metabolism and the brain are, in fact, connected by a common thread: clinical practice and a growing body of literature have now shown that obesity has a significant impact on the central nervous system (CNS), increasing the risk of neuropsychiatric disorders and dementia. In this context, intermittent fasting (IF), which entails consuming a balanced diet alternating with a 24-hour fast, would yield positive outcomes for both peripheral health and CNS health.
The researchers induced obesity in a mouse model by administering 10 weeks of a high-fat diet (HFD), followed by 4 weeks of intervention, and then compared the groups HFD, HFD-IF, ad libitum control feeding (CC) and CC-IF.
The results suggest that switching to CC or IF leads to a reduction in body weight, fat mass, and improved glucose tolerance. A finding of particular note concerns the ability of the CC-IF dietary model to foster a marked reduction in anxious behaviors. Obesity is a known risk factor for cardiometabolic diseases, including type 2 diabetes and hypertension, and at the brain level for an increased risk of cognitive disorders, neurodegenerative diseases, and neuropsychiatric conditions.
The collection of these data was possible thanks to transcriptomic techniques that allowed the detection of hippocampal neuroinflammation induced by HFD.
Instead, analyses and advanced metabolomics techniques identified a specific succinate signature in CC-IF mice, in which the plasma concentration was reduced, coupled with an increase in liver and brown adipose tissue (BAT) levels. This specialized fat, unlike white fat, burns calories to generate heat (thermogenesis), helping to maintain body temperature, especially in infants but present also in adults.
This suggests that succinate supplementation can mimic the metabolic and behavioral benefits of CC-IF and reduce hippocampal inflammation.
The Results
The findings show how regulating plasma succinate and its metabolism in the liver and BAT could, in the future, serve as a biochemical correlate underlying the metabolic, neuroinflammatory, and behavioral improvements driven by intermittent fasting.
On this basis, and with confirmation from further research, new treatment options could be developed.
The hypotheses include, for instance, nutritional or pharmacological approaches aimed at modulating succinate to prevent not only diabetes and other cardiometabolic diseases but also mood disorders and cognitive decline associated with obesity, offering neurobiological protection superior to that provided by simple calorie restriction.
Source
Tognozzi A, Carli F, Abdelkarim S et al. Succinate Modulation as a Biochemical Correlate of Metabolic and Neurobehavioral Changes Associated With Intermittent Fasting in Obesity. Acta Physiologica, 2026, 242(1):e70143. Doi: 10.1111/apha.70143.
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