We use cookies to enhance your experience. By continuing to browse this site you agree to our use of cookies. More info.

In a recent study published in the journal Nature, researchers explored the neural basis for fat preference and identified receptors and neuronal elements mediating its development.

Study: Gut-Brain Circuits for Fat Preference. Image Credit: Pikovit / Shutterstock

The current global obesity epidemic is a significant health problem. A high body-mass index (BMI) is a risk factor for stroke, diabetes, and several other diseases. Likewise, studies have linked the consumption of processed foods high in sugar and fat to multiple metabolic disorders and related comorbidities. Thus, a better understanding of the gut-to-brain mechanism that drives more fat consumption could inform the development of interventions to treat obesity and associated disorders. A previous study by Zuker's team demonstrated that sugar triggers signals from the gut to the brain, thereby fueling sweet cravings.

In the present study, researchers demonstrated that fat acts via the gut-brain axis to drive preference for fat after consumption.

First, they identified the vagal neurons responding to intestinal fat delivery using single-cell data. Next, the team recorded the activity of vagal neurons to alternating gut stimulation with fat (10 seconds of 10% linoleic acid) and sugar (10 s of 500 mM glucose) to examine how vagal neurons respond to these two nutrient signals in the gut. Remarkably, they evaluated over 1800 vagal sensory neurons from 22 nodoses.

Further, the researchers performed a series of experiments using mice for a comparative analysis of the gut-to-brain pathways driving preference for fat vs. sugar. The first set of experiments involved feeding test animals from two bottles — one containing an artificial sweetener, the other containing fat. Next, they dissected where the fat-sensing circuit is located in the brain to see its impact on the physiology and behavior of mice. They engineered mice that did not have neural receptors for detecting the presence of intestinal fat to validate the role of neurons as the mediators of gut-to-brain induced fat responses.

“The gut is the source of our great desire for fat and sugar,” -Charles S. Zuker, HHMI Investigator at Columbia University

Experiments with mice showed that after 48 hours, all mice preferred the bottle containing fat. This behavioral switch demonstrated that while artificial sweeteners send signals to the brain only after tasting but not after swallowing, fat continues to alert the brain post-ingestion even after it reaches the gut, thus driving our desire for it.

Further experiments using knock-out mice and various molecule-specific inhibitors revealed that fat sensing occurs sequentially. First, fat binds to receptors in the gut, which, in turn, transmits signals to neurons via the gut-brain axis. The bilaterally activated neurons in the caudal nucleus of the solitary tract (cNST) (in the brain stem) send a message to the whole brain that fat has been consumed. Notably, the fat-activated cNST neurons receive signals originating in the gut directly. Therefore, even intragastric infusion of fat in mice activates the cNST.

Bilateral vagotomy effectively obliterated fat-activated neural responses in the cNST, thus, establishing the vagus nerve as the channel of fat signal transmission from the gut to the brain. Intriguingly, the team identified two parallel gut-to-brain signaling pathways operated by two distinct groups of vagal neurons. Nearly 8% of more generic neurons responded to fat, sugar, and amino acids, while another ~8% of non-overlapping neurons got triggered only by intestinal fat. The results showed two distinct gut-brain circuits for intestinal fat sensing. However, both utilized the same receptors, GPR40 and GPR120, for driving the development of fat preference.

Studies have proposed that enteroendocrine cells (EECs) in the intestines employ cholecystokinin (CCK) as a neurotransmitter to send signals. To validate this, the researchers pharmacologically inhibited CCK signaling with Devazepide, a CCK-A receptor (CCKAR) antagonist. Remarkably, blocking CCK signaling obliterated all the responses of the vagal sugar/fat neurons, while the fat-only responses remained robust and reliable.

While studies have extensively studied the external sensing system for touch, taste, and smell in humans, interoception, i.e., how the body receives information from internal organs — is not well understood. The current study discovered a gut-to-brain circuit that governs preference for fat. Furthermore, the authors demonstrated that fat, like sugar, uses the gut-brain axis to drive consumption.

The study well delineated the innate attraction or liking for sweets and fats and 'wanting' them. While the former involves the taste system, the gut-brain axis is responsible for an unsatiable want for these two. Future studies should explore the basic biology behind the transmission of fat-triggered signals across the brain after reaching the brain stem to motivate people to consume more fat.

Posted in: Child Health News | Men's Health News | Medical Research News | Medical Condition News | Women's Health News | Disease/Infection News

Tags: Artificial Sweeteners, Brain, Cell, Diabetes, Glucose, Gut-Brain Axis, Linoleic Acid, Metabolic Disorders, Molecule, Nerve, Neurons, Obesity, Physiology, Receptor, Stroke, Swallowing

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

Please use one of the following formats to cite this article in your essay, paper or report:

Mathur, Neha. (2022, September 11). Study reveals gut-brain circuits drive cravings for fatty foods. News-Medical. Retrieved on October 09, 2022 from https://www.news-medical.net/news/20220911/Study-reveals-gut-brain-circuits-drive-cravings-for-fatty-foods.aspx.

Mathur, Neha. "Study reveals gut-brain circuits drive cravings for fatty foods". News-Medical. 09 October 2022. <https://www.news-medical.net/news/20220911/Study-reveals-gut-brain-circuits-drive-cravings-for-fatty-foods.aspx>.

Mathur, Neha. "Study reveals gut-brain circuits drive cravings for fatty foods". News-Medical. https://www.news-medical.net/news/20220911/Study-reveals-gut-brain-circuits-drive-cravings-for-fatty-foods.aspx. (accessed October 09, 2022).

Mathur, Neha. 2022. Study reveals gut-brain circuits drive cravings for fatty foods. News-Medical, viewed 09 October 2022, https://www.news-medical.net/news/20220911/Study-reveals-gut-brain-circuits-drive-cravings-for-fatty-foods.aspx.

In this interview, News-Medical speaks to Li Ye, P.h.D about his latest research which identified sensory neurons that carry a stream of messages from adipose tissue to the brain.

This interview from Bartels discusses how microfluidics will be used increasingly in labs, hospitals and doctors offices in the future. Bartels provides its clients with fast and easy entry into the microfluidics field.

In this interview, we speak to Mudra Kapoor, Vice President of Global Medical Affairs for Neuroscience at AbbVie, about atogepant, their new treatment option for migraine.

News-Medical.Net provides this medical information service in accordance with these terms and conditions. Please note that medical information found on this website is designed to support, not to replace the relationship between patient and physician/doctor and the medical advice they may provide.

This site complies with the HONcode standard for trustworthy health information: verify here.

News-Medical.net - An AZoNetwork Site

Owned and operated by AZoNetwork, © 2000-2022