The fight against obesity has been an ongoing battle for decades. With over one billion people worldwide affected by this condition, scientists are constantly seeking new and effective treatments. Recently, researchers at the Salk Institute have made a groundbreaking discovery that could potentially change the game. They’ve identified a tiny molecule called Adipocyte-smORF-1183, which plays a crucial role in regulating fat cell biology and lipid accumulation.

This breakthrough was made possible by using CRISPR gene editing to screen thousands of fat cell genes. The researchers found dozens of genes that likely code for microproteins involved in either fat cell proliferation or lipid accumulation. One of these potential microproteins, Adipocyte-smORF-1183, was verified to influence lipid droplet formation in fat cells.

The discovery of this molecule is a significant step towards understanding the complex energy storage system in our bodies. It also opens up new possibilities for developing targeted therapies that can specifically address obesity and related metabolic disorders.

While more research is needed to fully understand the implications of Adipocyte-smORF-1183, this breakthrough is a promising development in the fight against obesity. As scientists continue to study this molecule and its role in fat cell biology, we may see new and innovative treatments emerge that can help millions of people worldwide manage their weight and improve their overall health.

In related news, researchers at Scripps Research Institute have also been studying microproteins involved in fat cell differentiation and proliferation. Their work has identified several potential candidates for further investigation, which could lead to new therapeutic targets for obesity and metabolic disorders.

The study was supported by various grants from the National Institutes of Health, Ferring Foundation, Clayton Foundation, and Larry and Carol Greenfield Technology Fund. Further validation or screening of new cell libraries will expand the list of potential drug candidates, setting the stage for the new-and-improved obesity and metabolic disorder therapeutics of the future.

Scientists have made a groundbreaking discovery that could revolutionize the way we approach weight loss. A multidisciplinary team led by Robert Doyle, a chemistry professor at Syracuse University, has identified a hidden brain shortcut that can help people lose weight without experiencing nausea, a common side effect of current weight loss medications.

Current weight loss and diabetes drugs often target brain neurons that control appetite but frequently cause unpleasant side effects like nausea and vomiting. In fact, 70% of patients stop treatment within a year due to these side effects. Doyle’s team has been researching alternative targets for treating obesity and diabetes, looking beyond neurons to study “support” cells such as glia and astrocytes.

The research team discovered that 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 improve how they processed glucose. However, injecting directly into the brain isn’t a practical treatment for people.

To overcome this limitation, researchers created a new version of the molecule named tridecaneuropeptide (TDN), which 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.

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 support cells, which researchers found also produce appetite suppression. This approach has the potential to reduce the unpleasant side effects caused by GLP-1 drugs.

“The idea is to start the process halfway through, reducing the marathon of chemical reactions and negative side effects,” 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.”

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.

Their focus is on translating candidates into the clinic, aiming to start human trials in 2026 or 2027. This breakthrough has the potential to revolutionize the way we approach weight loss, providing a more comfortable and effective solution for millions of people worldwide.

The study, published in Nature Metabolism, reveals that consuming fewer calories is not the only way to improve health and lose weight. Researchers have discovered a specific sulfur-containing amino acid called cysteine as a key component in weight loss. When participants restricted their calorie intake, it resulted in reduced levels of cysteine in white fat cells.

The Pennington Biomedical researchers, Dr. Eric Ravussin and Dr. Krisztian Stadler, examined cysteine’s role in metabolism and found that it triggers the transition of white fat cells to brown fat cells. These more active fat cells burn energy to produce heat and maintain body temperature. When researchers restricted cysteine entirely in animal models, it drove high levels of weight loss and increased fat burning and browning of fat cells.

Dr. Stadler stated, “In addition to the dramatic weight loss and increase in fat burning resulting from the removal of cysteine, the amino acid is also central to redox balance and redox pathways in biology.” This suggests future weight management strategies that might not rely exclusively on reducing caloric intake.

The article is based on results from trials involving both human participants and animal models. For the human trials, researchers examined fat tissue samples taken from trial participants who had actively restricted calorie intake over a year. The exploration of these metabolites indicated a reduced level of cysteine.

Dr. Ravussin said, “Reverse translation of a human caloric restriction trial identified a new player in energy metabolism.” Systemic cysteine depletion in mice caused weight loss with increased fat utilization and browning of adipocytes.

The tissue samples came from participants in the CALERIE clinical trial, which recruited healthy young and middle-aged men and women who were instructed to reduce their calorie intake by an average of 14% over two years. With the reduction of cysteine, the participants also experienced subsequent weight loss, improved muscle health, and reduced inflammation.

In the animal models, researchers provided meals with reduced calories. This resulted in a 40% drop in body temperature, but regardless of the cellular stress, the animal models did not exhibit tissue damage, suggesting that protective systems may kick in when cysteine is low.

Dr. John Kirwan, Executive Director of Pennington Biomedical Research Center, stated, “Dr. Ravussin, Dr. Stadler, and their colleagues have made a remarkable discovery showing that cysteine regulates the transition from white to brown fat cells, opening new therapeutic avenues for treating obesity.” I would like to congratulate this research team on uncovering this important metabolic mechanism that could eventually transform how we approach weight management interventions.