A state-of-the-art study in the evolving landscape of metabolic research has unravelled a novel pathway in the brain that regulates fat absorption in the intestines. In Nature, this study from Qianqian Lyu and an international team of scientists puts to light the hidden role of the brain in how the body absorbs dietary fats.
This finding not only extends our knowledge concerning the role of the nervous system in digestion but also opens completely new perspectives in the fight against obesity and metabolic illnesses.
DMV: The Fat Absorption Manager of the Brain
DMV refers to the dorsal motor nucleus of the vagus, a region in the brainstem that plays a crucial role in controlling various digestive processes, including fat absorption. The DMV is part of the brain-to-gut communication pathway, influencing how the intestines absorb nutrients.
Fat absorption through the gut has classically been considered an organ-autonomous process, with diffusion being the main route of absorption, facilitated by protein-mediated transport mechanisms. However, this study takes a different turn to show the involvement of one key player in the brain-to-gut axis: the DMV.
The DMV, which is situated in the brainstem, already is known for influencing several digestive processes, including gastrointestinal motility and the digestion of food particles. However, this study really points out its direct influence on fat absorption. According to the study, manipulation of DMV neurons can also enhance or suppress the capability of the body for fat absorption. This discovery is a huge leap from the earlier thought that fat absorption was confined within the intestines and very little brain involvement occurred.
Neuronal Control Over Intestinal Absorption
In this regard, the researchers applied state-of-the-art techniques, including chemogenetic tools for the selective inactivation and activation of DMV neurons in mice. The result from such neurons showed that their inactivation resulted in animals having reduced fat absorption and lesser weight gain with increased fat excretion through faeces. Conversely, stimulation of the DMV neurons resulted in increased fat absorption, thus increased weight gain and a decrease in fat excretion.
Perhaps most strikingly—though peculiarly similar to what happens in the brain—this inactivation of DMV neurons directly affects the structure of intestinal microvilli, small finger-like projections lining the gut that help absorb nutrients. The shorter the microvilli, the less fat an intestine can absorb. Thus, by changing the DMV, the researchers could essentially control the length of the microvilli and, therefore, control how fat gets into the body.
The Role of Puerarin in Fat Regulation
The authors have identified, through their search a compound that could successfully mimic the inactivation of DMV, puerarin, which is a natural isoflavone compound from the root of the kudzu plant. Puerarin is a common medication used to treat cerebrovascular diseases and has emerged as a potent inhibitor of the DMV-vagus pathway. In mice receiving this, it suppressed fat absorption, shortened the length of intestinal microvilli, and caused weight loss with no disruption of food intake.
Applying such sophisticated techniques as photo-affinity labelling and cryogenic electron microscopy, the researchers found that puerarin binds to the α1 subunit of the GABAA receptor, known as GABRA1—this receptor is highly expressed in the DMV, its activation by puerarin would appear to be the key to its lowering effects on fat absorption.
Potential Anti-Obesity Implications
Results from this study are of great therapeutic potential, at least about the prevalence of obesity and metabolic disorders. Unlike anti-obesity medicines like **orlistat**, which inhibits fat absorption by blocking lipase enzymes—a reason it often produces gastrointestinal side effects like fatty diarrhoea—puerarin does this in a more sophisticated way: Puerarin targets the brain-to-gut axis and, in particular, modulates neuronal activity in the DMV as one means of achieving reduced fat absorption in a more gentle and possibly safe way.
It does indicate a sea change in obesity treatment, since most, if not all, anti-obesity drugs act either by directly interfering with digestive enzymes or by affecting brain circuits to reduce fat absorption. The authors say that future clinical studies will be necessary to determine the efficacy and safety of puerarin in humans, but the initial results are encouraging.
Brain-Gut Communication: A New Frontier
Not only does this deepen the insight into how the brain influences digestion, but it also expands the horizon against which the interaction between the brain and gut is projected. So far, it has been very little known exactly what the contribution of the brain is regarding fat absorption, the emphasis being placed on local gut processes. The current study, however, underlines how sensitive these absorption systems are to the signals from the brain, especially via pathways such as the DMV.
This present study has mapped the role of the brain in controlling gut functions, thus laying the bedrock for further investigations into how other nutrients might be similarly controlled by the same brain-gut circuits. These are questions regarding lifestyle impacts, stress, and neurological conditions on metabolic health via the same pathways.
Conclusion
The idea that the intestines have a way through which it signals via the DMV-vagus pathway when fat absorption in the intestines should be turned on or off changes the paradigm in understanding body metabolic processes. That the study was able to identify puerarin as such a therapeutic agent acting on this pathway to reduce fat absorption brings in a whole new level of intrigue into the implications it states for the treatment of obesity. As more and more research in this area is done, the brain and gut's complex dance would likely continue to give up secrets that may enable us to take better care of metabolic health or perhaps one day change the way we approach weight loss.
Sources:
Lyu, Q., Xue, W., Liu, R., Ma, Q., et al. "A brain-to-gut signal controls intestinal fat absorption." *Nature*.