The Rutgers Health researchers have made a groundbreaking discovery about how our brains process hunger and fullness cues. Two new studies, published in Nature Metabolism and Nature Communications, have mapped the first complementary wiring diagram of hunger and satiety in ways that could refine today’s blockbuster weight-loss drugs and blunt their side effects.

One study, led by Zhiping Pang of Robert Wood Johnson Medical School’s Center for NeuroMetabolism, pinpointed a slender bundle of neurons that runs from the hypothalamus to the brainstem. This pathway, known as GLP-1 receptors, is mimicked by weight-loss drugs such as Ozempic. When Pang’s team used optogenetics to fire axons with laser light, well-fed mice quit eating; when they silenced the circuit or deleted the receptor, the animals packed on weight.

The cells in this pathway bristle with GLP-1 receptors, which are proteins that play a key role in regulating energy balance. The study found that fasting weakened the connection until a burst of natural or synthetic GLP-1 restored it. Pang warns that drugs that keep the signal high around the clock could disrupt the brain’s normal rhythm and create some of the side effects of GLP-1 drugs, such as nausea, vomiting, constipation or diarrhea and muscle wasting.

For the other paper, Mark Rossi, who co-leads the Center for NeuroMetabolism with Pang, charted the circuit that triggers hunger. His group traced inhibitory neurons in the stria terminalis to similar cells in the lateral hypothalamus. When researchers triggered the connection, a suddenly hungry mouse would sprint for sugar water; when they blocked it, the animals lounged even after a long fast.

Hormones modulated the effect. An injection of ghrelin, the gut’s hunger messenger, revved food seeking, while leptin, the satiety signal, slammed it shut. Overfed mice gradually lost the response, but it returned after diets made them thin again.

Pang’s pathway shuts things down,” Rossi said. “Ours steps on the accelerator.” Although the circuits sit in different corners of the brain, members of both teams saw the same principle: Energy state rewires synapses quickly. During a fast, the hunger circuit gains sensitivity while the satiety circuit loosens; after a meal, the relationship flips.

It is the first time researchers have watched the push-pull mechanism operate in parallel pathways, a yin-yang arrangement that may explain why diets and drugs that treat only one side of the equation often lose power over time. The studies suggest a therapy targeting only the brainstem circuit and sparing peripheral organs might curb eating without the side effects.

Conversely, Rossi’s work hints that restoring the body’s response to the hunger-regulating hormone ghrelin could help dieters who plateau after months of calorie cutting. Both projects relied on the modern toolkit of neural biology – optogenetics to fire axons with laser light, chemogenetics to silence them, fiber-optic photometry to watch calcium pulses and old-fashioned patch-clamp recordings to monitor single synapses.

Follow-up work from both teams will explore more questions that could improve drug design. Pang wants to measure GLP-1 release in real time to see whether short bursts, rather than constant exposure, are enough to calm appetite. Rossi is cataloging the molecular identity of his hunger-trigger cells in hopes of finding drug targets that steer craving without crushing the joy of eating.

“You want to keep the system’s flexibility,” Rossi said. “It’s the difference between dimming the lights and flicking them off.”

Unlocking Nature’s Secrets: Scientists Discover Natural Cancer-Fighting Sugar in Sea Cucumbers

In a groundbreaking study, researchers from the University of Mississippi and Georgetown University have discovered a natural sugar compound found in sea cucumbers that can effectively block Sulf-2, an enzyme crucial for cancer growth. This breakthrough has significant implications for the development of new cancer therapies.

The research team, led by Marwa Farrag, a fourth-year doctoral candidate in the UM Department of BioMolecular Sciences, worked tirelessly to isolate and study the sugar compound, fucosylated chondroitin sulfate, from the sea cucumber Holothuria floridana. This unique sugar is not commonly found in other organisms, making it an exciting area of research.

Human cells are covered in tiny, hairlike structures called glycans that help with cell communication, immune responses, and the recognition of threats such as pathogens. Cancer cells alter the expression of certain enzymes, including Sulf-2, which modifies the structure of glycans, helping cancer spread. By inhibiting this enzyme, researchers believe they can effectively fight against the spread of cancer.

Using both computer modeling and laboratory testing, the research team found that the sugar compound from sea cucumbers can effectively inhibit Sulf-2, a promising step towards developing new cancer therapies. This natural source is particularly appealing as it does not carry the risk of transferring viruses and other harmful agents, unlike extracting carbohydrate-based drugs from pigs or other land mammals.

While this discovery holds great promise, the researchers acknowledge that further study is needed to develop a viable treatment. One of the challenges lies in finding a way to synthesize the sugar compound for future testing. The interdisciplinary nature of the scientific study highlights the importance of cross-disciplinary collaboration in tackling complex diseases like cancer.

This groundbreaking research has far-reaching implications for the medical field and demonstrates the power of scientific discovery in unlocking nature’s secrets. As researchers continue to explore this area, they may uncover new therapies that can effectively combat cancer, ultimately saving lives and improving patient outcomes.

The quest for a cure to cancer has led scientists to explore the depths of nature, seeking answers that can unlock the secrets of this complex disease. One such natural compound is found in kencur ginger, which has shown promise in targeting the metabolic pathway of cancer cells.

In normal human cells, energy is produced through the oxidation of glucose, resulting in the production of ATP (adenosine triphosphate), the primary energy source necessary for life. However, cancer cells take a different approach, using glycolysis to produce ATP even when oxygen is present. This inefficient method, known as the Warburg effect, has puzzled scientists, leading them to wonder why cancer cells choose this pathway.

Associate Professor Akiko Kojima-Yuasa and her team at Osaka Metropolitan University’s Graduate School of Human Life and Ecology have been investigating the cinnamic acid ester ethyl p-methoxycinnamate, a main component of kencur ginger. Their previous research revealed that this compound has inhibitory effects on cancer cells. The team decided to further their study by administering the acid ester to Ehrlich ascites tumor cells, which resulted in some unexpected findings.

The researchers discovered that ethyl p-methoxycinnamate not only disrupts de novo fatty acid synthesis and lipid metabolism but also triggers increased glycolysis as a possible survival mechanism in the cells. This adaptability was theorized to be attributed to the compound’s inability to induce cell death.

“These findings not only provide new insights that supplement and expand the theory of the Warburg effect, which can be considered the starting point of cancer metabolism research, but are also expected to lead to the discovery of new therapeutic targets and the development of new treatment methods,” stated Professor Kojima-Yuasa.

The study’s results have significant implications for cancer research, opening up new avenues for investigation into the metabolic pathways of cancer cells. As scientists continue to explore the mysteries of nature, they may uncover even more secrets that can lead to a deeper understanding and potential cures for this complex disease.