Blog

For cancer- and infection-fighting T cells, glucose offers far more than a simple sugar rush.

A new discovery by Van Andel Institute scientists reveals that glucose, an essential cellular fuel that powers immune cells, also aids in T cells’ internal communication and boosts their cancer-fighting properties. The findings may help optimize T cells’ ability to combat cancer and other diseases.

A study describing the work published today in Cell Metabolism.

“Immune cells are highly influenced by their environment” said Joseph Longo, Ph.D., the study’s first author and a postdoctoral fellow in the lab of Russell Jones, Ph.D. “We knew that T cells need access to glucose to function, but we didn’t know exactly why. It was previously thought that T cells mainly break down glucose for energy, but our new work shows that T cells use glucose as a building block for other molecules that are necessary to support T cells’ anti-cancer properties.”

The findings reveal that T cells allocate significant portions of glucose to build large molecules called glycosphingolipids (GSLs). These sugar-fat compounds are essential for T cell growth and making proteins that T cells use to combat cancer.

GSLs help form fat-rich structures on T cell surfaces called lipid rafts, which bring together cell signaling proteins that instruct the T cell to kill cancer cells. Without GSLs, these signals are weaker, making T cells less effective at destroying tumors.

Both T cells and cancer cells leverage different nutrients to support varying aspects of their function. The more we know about these different fuel sources, the better we can support T cells’ innate cancer-fighting abilities while also developing ways to possibly make cancer cells more vulnerable to immune attack.”

Russell Jones, Ph.D., Van Andel Research Institute

Do you find yourself reaching for a cup of coffee at night to stay alert? A new study from The University of Texas at El Paso suggests you might want to reconsider. A team of UTEP biologists have discovered that nighttime caffeine consumption can increase impulsive behavior, potentially leading to reckless actions.

The study, published in iScience, examined how nighttime caffeine intake affects inhibition and impulsivity in fruit flies and was led by Erick Saldes, Ph.D., Paul Sabandal, Ph.D., and Kyung-An Han, Ph.D. Drosophila melanogaster, the fruit fly species used in the study, is a powerful model to study complex behaviors due to its genetic and neural parallels with humans, said Han.

Caffeine is the most widely consumed psychoactive substance in the world, with about 85% of adults in the U.S. using it regularly. Given caffeine’s popularity, we wanted to explore whether additional factors influence its impact on behavioral control.”

Paul Sabandal, Ph.D., research assistant professor in UTEP’s Department of Biological Sciences

The team designed a series of experiments introducing caffeine into the flies’ diets under various conditions, including different caffeine doses, nighttime versus daytime consumption and in combination with sleep deprivation. The team then assessed impulsivity by measuring the flies’ ability to suppress movement in response to strong airflow, a naturally unpleasant stimulus.

“Under normal circumstances, flies stop moving when exposed to strong airflow,” said Saldes, now a science research specialist at the University of Illinois College of Medicine Peoria and a former doctoral student at UTEP. “We found that flies consuming caffeine at night were less able to suppress movement, displaying impulsive behaviors such as reckless flying despite these aversive conditions.”

Interestingly, caffeine consumed by the flies during the daytime did not lead to the same reckless flying, the team said.

The team also discovered notable sex differences. Despite having comparable levels of caffeine in the body, females exhibited significantly greater caffeine-induced impulsivity than males.

“Flies don’t have human hormones like estrogen, suggesting that other genetic or physiological factors are driving the heightened sensitivity in females,” said Biological Sciences Professor Kyung-An Han. “Uncovering these mechanisms will help us better understand how nighttime physiology and sex-specific factors modulate caffeine’s effects.”

The team warns that the findings could have negative implications for shift workers, health care and military personnel who consume coffee at night, particularly females.

This study was conducted in Han’s lab within UTEP’s Department of Biological Sciences. The lab focuses on the neurobiological basis of behavioral plasticity including learning, memory and addiction as well as gene-by-environment interactions relevant to Alzheimer’s disease and related dementia.

A total of 250 one-day-old male broiler chickens were raised for 35 days in five separate groups.

One of the groups was challenged with E.coli and had supplements of 3% fermented chives (FC3) to assess it as an alternative to antibiotics.

This group showed significantly improved growth performance in terms of higher body weight gain, feed intake, survival rate, and production efficiency.

“The FC3 group achieved weight gain and feed intake levels comparable to those of the antibiotic (AB) and negative control (NC) groups, with significantly higher values than the positive control (PC) group.”

Additionally, the researchers observed enhanced immune responses, stronger intestinal barrier, and balanced inflammatory response.

The treatment was found to be very effective at reducing E.coli and Salmonella while increasing beneficial Lactobacillus.

“The observed performance improvements may be linked to bioactive compounds present in chive, such as polyphenols, flavonoids, and organosulfur compounds, known for their antioxidant, anti-inflammatory, and antimicrobial properties. These compounds potentially inhibit E. coli proliferation in the gastrointestinal tract, thereby enhancing gut health and supporting growth,” said the study.

It concluded that fermented chives could serve as a promising antibiotic alternative in poultry farming.

“Fermented chive represents a promising antibiotic alternative in poultry farming, contributing to intestinal disease control and sustainable livestock production.”

Boosting chive efficacy with probiotics

The researchers fermented chives (Allium schoenoprasum) with Lactobacillus plantarum 1582 to create the additive.

According to the paper, chives are rich in flavonoids such as quercetin and organosulfur compounds.

However, it was necessary to ferment the chives to enhance its bioactivity by increasing the release of polyphenols, free amino acids, and organosulfur compounds while also boosting antioxidant properties.

Fermentation would also encourage the proliferation of beneficial gut bacteria to benefit the overall gut health.

One of the authors from this study previously isolated L. plantarum 1582 from free-range native chicken faeces.

It was found to have “superior probiotic properties” among other strains and capable of E. coli inhibition.

The researchers said selecting the right strain was crucial to “maximising the benefits” of chives.

“Interestingly, fermentation not only preserves active compounds but also generates by-products, such as short-chain fatty acids, which nourish epithelial cells and maintain intestinal mucosal integrity,” they observed.

According to the researchers, FC3 also functions as a synbiotic, combining the prebiotics from chives and probiotics from the L. plantarum fermentation.

“This synbiotic effect promotes the survival of beneficial gut bacteria, increases lactic acid production to lower intestinal pH, and inhibits pathogenic E. coli. Chive also provides nutrients for beneficial bacteria, supporting microbiota balance, improving digestion, and enhancing growth performance.”

Source: Fermentation

Fermented Chive (Allium schoenoprasum) with Lactobacillus plantarum: A Potential Antibiotic Alternative Feed Additive for Broilers Challenged with Escherichia coli

Authors: Phan Vu Hai, Le Xuan Anh, and Nguyen Xuan Hoa

https://doi.org/10.3390/fermentation11050277

Weight loss and diabetes drugs on the market often do not achieve long-term weight loss for patients. GLP-1 drugs target brain neurons that control appetite but frequently cause side effects. Nausea and vomiting force 70% of patients to stop treatment within a year. Syracuse University chemistry professor Robert Doyle is leading a multidisciplinary team that has identified a different brain target for treating obesity and diabetes, potentially offering weight loss without gastrointestinal distress.

Neurons are the most well-known and obvious target in research and drug development for brain conditions. GLP-1 drugs, for example, target brain neurons in the hindbrain involved in appetite control. But researchers are looking beyond neurons to study “support” cells such as glia and astrocytes that could aid appetite reduction.

A collaborative research effort has revealed that support cells play a role in reducing feelings of hunger, although this process has not been studied in-depth.

“We wanted to know whether support cells might produce new peptides or new signaling molecules that might be critical in body weight reduction,” says Doyle, a medicinal chemist and the Jack and Laura H. Milton Professor of Chemistry in the College of Arts and Sciences at Syracuse University. Doyle is also a professor of pharmacology and medicine at SUNY Upstate Medical University.

How it works

Think of each brain neuron as a light bulb and support cells as the components that allow the light bulb to brighten, including the wiring, switch and filament.

All of those supporting parts beyond the light bulb play a role in making the light shine.”

Robert Doyle, chemistry professor, Syracuse University 

The research team discovered that some support cells in the hindbrain naturally produce a molecule named octadecaneuropeptide (ODN), which suppresses appetite. In lab tests, injecting ODN directly into rats’ brains made them lose weight and improved how they processed glucose.

However, injecting directly into the brain isn’t a practical treatment for people, so researchers created a new version of the molecule named tridecaneuropeptide (TDN). This molecule version could be given to human patients through regular injections akin to today’s Ozempic or Zepbound. When tested in obese mice and musk shrews, TDN helped the animals lose weight and respond better to insulin without causing nausea or vomiting.

Marathon shortcut

One goal of the research team is to produce weight loss without aiming new therapeutic molecules at neurons. The new TDN molecule bypasses neurons, taking a shortcut to directly target neurons’ downstream support cells, which researchers found also produce appetite suppression. TDN cuts short the “marathon” of chemical reactions and negative side-effects caused by GLP-1 drugs.

“Instead of running a marathon from the very beginning like current drugs do, our targeting downstream pathways in support cells is like starting the race halfway through, reducing the unpleasant side effects many people experience,” says Doyle. “If we could hit that downstream process directly, then potentially we wouldn’t have to use GLP-1 drugs with their side effects. Or we could reduce their dose, improving the toleration of these drugs. We could trigger weight loss signals that happen later in the pathway more directly.”

A new company called CoronationBio has been launched to turn this discovery into a real-world treatment. The company has licensed intellectual property related to ODN derivatives for the treatment of obesity and cardio-metabolic disease from Syracuse University and the University of Pennsylvania, with a focus on translating candidates into the clinic. They’re now teaming up with other companies to develop this treatment and aim to start human trials in 2026 or 2027.