Researchers at Scripps Research have discovered that fasting can convey information to the brain beyond just caloric withdrawal in a study involving the C. elegans worm. This small organism showed that a molecule produced by the intestines during fasting travels to the brain to block a fat-burning signal, slowing down the rate of fat loss. The identification of this molecule sheds light on the complex communication between the gut and the brain, potentially explaining why fasting has health benefits independent of calorie intake. While the molecule has not been studied in humans, the findings could have implications for health outcomes associated with fasting in other animals, including mammals.
The brain is known to control the production and breakdown of fats in various organisms, including humans and C. elegans. Previous research identified a brain hormone called FLP-7 that triggers fat burning in the worm’s gut. However, the reverse communication pathway from the gut to the brain had not been fully understood. In the recent study, researchers removed over 100 signaling molecules from the worm’s intestines and discovered that a form of insulin known as INS-7 had a significant impact on the brain’s production of FLP-7. This insulin molecule, produced by gut cells, was found to regulate fat metabolism in the brain, despite its more well-known role in controlling blood sugar levels in humans.
The role of INS-7 in impacting brain cells was found to be unique, as it did not activate insulin receptors like other insulin molecules. Instead, INS-7 blocked the insulin receptor, triggering a cascade of molecular events that ultimately halted the production of the fat-burning hormone FLP-7 in the brain. The researchers described INS-7 as a signal from the intestines instructing the brain to preserve fat stores due to a lack of incoming food. This study provides insight into how an empty gut can communicate with the brain and potentially influence various aspects of health beyond fat regulation.
The findings from this study deepen our understanding of the bidirectional communication between the brain and the digestive system in controlling metabolism based on food availability. The researchers suggest that compounds mimicking gut hormones, such as semaglutide, could be further explored for their potential in controlling obesity and diabetes based on the insights gained from this research. Future studies will investigate how INS-7 is produced in C. elegans gut cells during fasting and which brain cells are affected by the molecule. The discovery of new gut peptides could potentially lead to the development of novel drugs targeting metabolic regulation.
This research was supported by funding from the National Institutes of Health and highlights the significance of studying simple model organisms like C. elegans to unravel complex biological processes. By elucidating the mechanisms behind fasting-induced changes in the body, this study paves the way for further investigations into the health benefits of fasting and potential therapeutic strategies for metabolic disorders. The intricate interplay between the gut and the brain in regulating metabolism opens up new avenues for research and the development of innovative approaches to addressing obesity and related conditions.
