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KAIST Shows That the Brain Can Distinguish Glucose: Clues to Treat Obesity and Diabetes
<(From left)Prof. Greg S.B Suh, Dr. Jieun Kim, Dr. Shinhye Kim, Researcher Wongyo Jeong)
“How does our brain distinguish glucose from the many nutrients absorbed in the gut?” Starting with this question, a KAIST research team has demonstrated that the brain can selectively recognize specific nutrients—particularly glucose—beyond simply detecting total calorie content. This study is expected to offer a new paradigm for appetite control and the treatment of metabolic diseases.
On the 9th, KAIST (President Kwang Hyung Lee) announced that Professor Greg S.B. Suh’s team in the Department of Biological Sciences, in collaboration with Professor Young-Gyun Park’s team (BarNeuro), Professor Seung-Hee Lee’s team (Department of Biological Sciences), and the Albert Einstein College of Medicine in New York, had identified the existence of a gut-brain circuit that allows animals in a hungry state to selectively detect and prefer glucose in the gut.
Organisms derive energy from various nutrients including sugars, proteins, and fats. Previous studies have shown that total caloric information in the gut suppresses hunger neurons in the hypothalamus to regulate appetite. However, the existence of a gut-brain circuit that specifically responds to glucose and corresponding brain cells had not been demonstrated until now.
In this study, the team successfully identified a “gut-brain circuit” that senses glucose—essential for brain function—and regulates food intake behavior for required nutrients.
They further proved, for the first time, that this circuit responds within seconds to not only hunger or external stimuli but also to specific caloric nutrients directly introduced into the small intestine, particularly D-glucose, through the activity of “CRF neurons*” in the brain’s hypothalamus.
*CRF neurons: These neurons secrete corticotropin-releasing factor (CRF) in the hypothalamus and are central to the hypothalamic-pituitary-adrenal (HPA) axis, the body’s core physiological system for responding to stress. CRF neurons are known to regulate neuroendocrine balance in response to stress stimuli.
Using optogenetics to precisely track neural activity in real time, the researchers injected various nutrients—D-glucose, L-glucose, amino acids, and fats—directly into the small intestines of mice and observed the results.
They discovered that among the CRF neurons located in the paraventricular nucleus (PVN)* of the hypothalamus, only those specific to D-glucose showed selective responses. These neurons did not respond—or showed inverse reactions—to other sugars or to proteins and fats. This is the first demonstration that single neurons in the brain can guide nutrient-specific responses depending on gut nutrient influx.
*PVN (Paraventricular Nucleus): A key nucleus within the hypothalamus responsible for maintaining bodily homeostasis.
The team also revealed that glucose-sensing signals in the small intestine are transmitted via the spinal cord to the dorsolateral parabrachial nucleus (PBNdl) of the brain, and from there to CRF neurons in the PVN. In contrast, signals for amino acids and fats are transmitted to the brain through the vagus nerve, a different pathway.
In optogenetic inhibition experiments, suppressing CRF neurons in fasting mice eliminated their preference for glucose, proving that this circuit is essential for glucose-specific nutrient preference.
This study was inspired by Professor Suh’s earlier research at NYU using fruit flies, where he identified “DH44 neurons” that selectively detect glucose and sugar in the gut. Based on the hypothesis that hypothalamic neurons in mammals would show similar functional responses to glucose, the current study was launched.
To test this hypothesis, Dr. Jineun Kim (KAIST Ph.D. graduate, now at Caltech) demonstrated during her doctoral research that hungry mice preferred glucose among various intragastrically infused nutrients and that CRF neurons exhibited rapid and specific responses.
Along with Wongyo Jung (KAIST B.S. graduate, now Ph.D. student at Caltech), they modeled and experimentally confirmed the critical role of CRF neurons. Dr. Shinhye Kim, through collaboration, revealed that specific spinal neurons play a key role in conveying intestinal nutrient information to the brain.
Dr. Jineun Kim and Dr. Shinhye Kim said, “This study started from a simple but fundamental question—‘How does the brain distinguish glucose from various nutrients absorbed in the gut?’ We have shown that spinal-based gut-brain circuits play a central role in energy metabolism and homeostasis by transmitting specific gut nutrient signals to the brain.”
Professor Suh added, “By identifying a gut-brain pathway specialized for glucose, this research offers a new therapeutic target for metabolic diseases such as obesity and diabetes. Our future research will explore similar circuits for sensing other essential nutrients like amino acids and fats and their interaction mechanisms.”
Ph.D. student Jineun Kim, Dr. Shinhye Kim, and student Wongyo Jung (co-first authors) contributed to this study, which was published online in the international journal Neuron on June 20, 2025.
※ Paper Title: Encoding the glucose identity by discrete hypothalamic neurons via the gut-brain axis ※ DOI: https://doi.org/10.1016/j.neuron.2025.05.024
This study was supported by the Samsung Science & Technology Foundation, the National Research Foundation of Korea (NRF) Leader Research Program, the POSCO Cheongam Science Fellowship, the Asan Foundation Biomedical Science Scholarship, the Institute for Basic Science (IBS), and the KAIST KAIX program.
2025.07.09 View 265 -
A Single, Master Switch for Sugar Levels?
When a fly eats sugar, a single brain cell sends simultaneous messages to stimulate one hormone and inhibit another to control glucose levels in the body. Further research into this control system with remarkable precision could shed light on the neural mechanisms of diabetes and obesity in humans .
A single neuron appears to monitor and control sugar levels in the fly body, according to research published this week in Nature. This new insight into the mechanisms in the fly brain that maintain a balance of two key hormones controlling glucose levels, insulin and glucagon, can provide a framework for understanding diabetes and obesity in humans.
Neurons that sense and respond to glucose were identified more than 50 years ago, but what they do in our body has remained unclear. Researchers at the Korea Advanced Institute of Science and Technology (KAIST) and New York University School of Medicine have now found a single “glucose-sensing neuron” that appears to be the master controller in Drosophila, the vinegar fly, for maintaining an ideal glucose balance, called homeostasis.
Professor Greg Seong-Bae Suh, Dr. Yangkyun Oh and colleagues identified a key neuron that is excited by glucose, which they called CN neuron. This CN neuron has a unique shape – it has an axon (which is used to transmit information to downstream cells) that is bifurcated. One branch projects to insulin-producing cells, and sends a signal triggering the secretion of the insulin equivalent in flies. The other branch projects to glucagon-producing cells and sends a signal inhibiting the secretion of the glucagon equivalent.
When flies consume food, the levels of glucose in their body increase; this excites the CN neuron, which fires the simultaneous signals to stimulate insulin and inhibit glucagon secretion, thereby maintaining the appropriate balance between the hormones and sugar in the blood. The researchers were able to see this happening in the brain in real time by using a combination of cutting-edge fluorescent calcium imaging technology, as well as measuring hormone and sugar levels and applying highly sophisticated molecular genetic techniques.
When flies were not fed, however, the researchers observed a reduction in the activity of CN neuron, a reduction in insulin secretion and an increase in glucagon secretion. These findings indicate that these key hormones are under the direct control of the glucose-sensing neuron. Furthermore, when they silenced the CN neuron rendering dysfunctional CN neuron in flies, these animals experienced an imbalance, resulting in hyperglycemia – high levels of sugars in the blood, similar to what is observed in diabetes in humans. This further suggests that the CN neuron is critical to maintaining glucose homeostasis in animals.
While further research is required to investigate this process in humans, Suh notes this is a significant step forward in the fields of both neurobiology and endocrinology.
“This work lays the foundation for translational research to better understand how this delicate regulatory process is affected by diabetes, obesity, excessive nutrition and diets high in sugar,” Suh said.
Profile: Greg Seong-Bae Suh
seongbaesuh@kaist.ac.kr
Professor Department of Biological Sciences
KAIST
(Figure: A single glucose-excited CN neuron extends bifurcated axonal branches,
one of which innervates insulin producing cells and stimulates their activity an the other axonal branch projects to glucagon producing cells and inhibits their activity.)
2019.10.24 View 19244 -
Efficiently Producing Fatty Acids and Biofuels from Glucose
Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.
The newly developed strain, created by Distinguished Professor Sang Yup Lee and his team, showed the highest efficiency in producing fatty acids and biodiesels ever reported. It will be expected to serve as a new platform to sustainably produce a wide array of fatty acid-based products from glucose and other carbon substrates.
Fossil fuels, which have long been energy resources for our daily lives, are now facing serious challenges: depletion of their reserves and their role in global warming. The production of sustainable bio-based renewable energy has emerged as an essential alternative and many studies to replace fossil fuels are underway. One of the representative examples is biodiesel. Currently, it is mainly being produced through the transesterification of vegetable oils or animal fats.
The research team engineered oleaginous microorganisms, Rhodococcus opacus, to produce fatty acids and their derivatives that can be used as biodiesel from glucose, one of the most abundant and cheap sugars derived from non-edible biomass.
Professor Lee’s team has already engineered Escherichia coli to produce short-chain hydrocarbons, which can be used as gasoline (published in Nature as the cover paper in 2013). However, the production efficiency of the short-chain hydrocarbons using E. coli (0.58 g/L) fell short of the levels required for commercialization.
To overcome these issues, the team employed oil-accumulating Rhodococcus opacus as a host strain in this study. First, the team optimized the cultivation conditions of Rhodococcus opacus to maximize the accumulation of oil (triacylglycerol), which serves as a precursor for the biosynthesis of fatty acids and their derivatives. Then, they systematically analyzed the metabolism of the strain and redesigned it to enable higher levels of fatty acids and two kinds of fatty acid-derived biodiesels (fatty acid ethyl esters and long-chain hydrocarbons) to be produced.
They found that the resulting strains produced 50.2, 21.3, and 5.2 g/L of fatty acids, fatty acid ethyl esters, and long-chain hydrocarbons, respectively. These are all the highest concentrations ever reported by microbial fermentations. It is expected that these strains can contribute to the future industrialization of microbial-based biodiesel production.
“This technology creates fatty acids and biodiesel with high efficiency by utilizing lignocellulose, one of the most abundant resources on the Earth, without depending on fossil fuels and vegetable or animal oils. This will provide new opportunities for oil and petroleum industries, which have long relied on fossil fuels, to turn to sustainable and eco-friendly biotechnologies,” said Professor Lee.
This paper titled “Engineering of an oleaginous bacterium for the production of fatty acids and fuels” was published in Nature Chemical Biology on June 17.
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557).
(Figure: Metabolic engineering for the production of free fatty acids (FFAs), fatty acid ethyl esters (FAEEs), and long-chain hydrocarbons (LCHCs) in Rhodococcus opacus PD630. Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.)
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Source:
Hye Mi Kim, Tong Un Chae, So Young Choi, Won Jun Kim and Sang Yup Lee. Engineering of an oleaginous bacterium for the production of fatty acids and fuels. Nature Chemical Biology ( https://www.nature.com/nchembio/ ) DOI: 10.1038/s41589-019-0295-5
Profile
Dr. Sang Yup Lee
leesy@kaist.ac.kr
Distinguished Professor at the Department of Chemical and Biomolecular Engineering
KAIST
2019.06.19 View 52322