A natural compound from licorice called liquiritigenin reduced insulin resistance in obese mice by calming inflamed immune cells in fat tissue, according to Gram Research analysis of a 2026 study. The compound worked by reducing harmful molecules in immune cell mitochondria and restoring proper energy production, which prevented these cells from attacking fat cells and damaging their ability to respond to insulin. The effects were stronger than some common anti-inflammatory medications in laboratory tests.
Scientists discovered that a natural compound found in licorice called liquiritigenin may help fight obesity and improve how your body handles blood sugar. In studies with mice on high-fat diets, the compound worked by calming down immune cells in fat tissue that were causing inflammation and insulin resistance. According to Gram Research analysis, liquiritigenin reduced harmful molecules in mitochondria (the energy factories inside cells) and restored proper energy production, which helped fat cells respond better to insulin. The compound appeared to work even better than some common anti-inflammatory medications tested in the same experiments.
Key Statistics
A 2026 research article found that liquiritigenin improved glucose tolerance and insulin sensitivity in high-fat diet-fed mice by suppressing pro-inflammatory immune cell polarization through mitochondrial reactive oxygen species reduction.
In laboratory experiments, liquiritigenin’s protective effects against insulin resistance were more pronounced than dexamethasone, a standard anti-inflammatory medication, when tested under identical conditions.
The 2026 study demonstrated that palmitic acid (a saturated fat) triggered harmful immune cell inflammation in adipose tissue not through direct fat cell damage, but by increasing mitochondrial reactive oxygen species and disrupting energy production in macrophages.
The Quick Take
- What they studied: Whether a natural licorice compound could reverse insulin resistance and obesity in mice fed high-fat diets, and how it works inside the body
- Who participated: Laboratory mice fed high-fat diets to create obesity and insulin resistance, plus immune cells and fat cells studied in controlled lab conditions
- Key finding: Liquiritigenin improved glucose tolerance and insulin sensitivity by reducing harmful molecules in immune cells, which then stopped attacking fat cells and allowed them to work properly again
- What it means for you: This research suggests a natural compound might help people with obesity-related blood sugar problems, but human studies are needed before it can be recommended as a treatment
The Research Details
Researchers used multiple approaches to understand how liquiritigenin works. First, they gave obese mice the compound and measured changes in their blood sugar control, insulin sensitivity, and fat tissue health. They used advanced genetic and chemical analysis tools to track exactly which pathways in the body were affected. They also created a laboratory system where immune cells and fat cells were grown together to watch how liquiritigenin changed their interaction. This combination of whole-animal studies, genetic analysis, and cell culture experiments allowed them to identify the specific mechanism of action.
The key innovation was discovering that the problem wasn’t directly in the fat cells themselves, but in immune cells (macrophages) living in fat tissue. These immune cells were becoming inflamed and damaging the fat cells’ ability to respond to insulin. The researchers traced this back to a specific problem: harmful molecules called reactive oxygen species building up in the mitochondria of immune cells, disrupting their energy production.
To prove this was the real mechanism, they used special chemicals that either blocked or activated these harmful molecules. When they blocked them, the benefits appeared; when they activated them, the benefits disappeared. This type of proof is considered strong evidence that they found the true cause.
Understanding the exact mechanism is crucial because it explains why liquiritigenin works and suggests it could be developed into a real medicine. Rather than just treating symptoms, this approach targets the root cause of obesity-related insulin resistance: inflammation in immune cells. This is important because current treatments often have side effects, and a natural compound might offer a gentler alternative.
This study used multiple complementary research methods (multi-omics), which strengthens confidence in the findings. The researchers included proper control groups and used specific molecular tools to prove cause-and-effect relationships. However, this is animal research, so results may not directly translate to humans. The study was published in a peer-reviewed scientific journal, indicating it passed expert review. The specific sample size for animal studies wasn’t clearly stated in the abstract, which is a minor limitation.
What the Results Show
Liquiritigenin significantly improved how well mice’s bodies handled glucose (blood sugar) and responded to insulin after being fed high-fat diets. The compound restored normal levels of key proteins involved in insulin signaling—specifically p-IRS1, p-AKT, and GLUT4—which are like the locks and keys that allow glucose to enter cells. In the fat tissue, liquiritigenin reversed the harmful changes caused by the high-fat diet, including oxidative stress (cellular damage from harmful molecules), broken mitochondria, and inflammatory pathways.
The breakthrough finding was understanding how this worked: the compound reduced harmful reactive oxygen species (mtROS) in the mitochondria of immune cells called macrophages. These immune cells were being damaged by the high-fat diet, which caused them to switch into an inflammatory mode (called M1 polarization) that attacked fat cells. By restoring proper energy production in these immune cells, liquiritigenin prevented this inflammatory switch and allowed fat cells to respond normally to insulin again.
When researchers used special chemicals to block the harmful molecules, liquiritigenin’s benefits appeared. When they used chemicals to activate these harmful molecules, the benefits disappeared. This proves that the mitochondrial damage pathway is the real mechanism. Remarkably, liquiritigenin’s effects were stronger than dexamethasone, a common anti-inflammatory medication tested under identical conditions.
The research showed that liquiritigenin also improved overall lipid metabolism (how the body processes fats), suggesting benefits beyond just blood sugar control. The compound restored proper function of oxidative phosphorylation (OXPHOS), which is the main way cells produce energy in their mitochondria. This restoration of energy production in immune cells appears to be the key to preventing inflammation. The study also demonstrated that the problem in obesity isn’t that fat cells are inherently broken, but that immune cells in fat tissue become dysfunctional and damage the fat cells from the outside.
Previous research suggested that liquiritigenin had metabolic benefits, but the specific mechanism was unknown. This study fills that gap by identifying the mitochondrial dysfunction in immune cells as the critical problem. The finding that immune cell inflammation, rather than direct fat cell damage, drives insulin resistance aligns with growing evidence in obesity research that immune system dysfunction is central to metabolic disease. The comparison to dexamethasone is notable because it suggests a natural compound might match or exceed pharmaceutical anti-inflammatory drugs.
This research was conducted in mice, not humans, so results may not directly apply to people. The study didn’t test different doses of liquiritigenin to find optimal amounts. The specific number of animals used wasn’t stated in the abstract. The research was done in laboratory conditions that may not perfectly reflect the complexity of living organisms. Long-term safety and effectiveness in humans remain unknown. The study doesn’t address whether liquiritigenin could help people who are already obese, or only prevent obesity from developing.
The Bottom Line
Based on this research, liquiritigenin shows promise as a potential treatment for obesity-related insulin resistance, but it’s not ready for human use yet. The evidence is strong for the mechanism (how it works) but limited to animal studies. Anyone interested in this compound should wait for human clinical trials before considering it as a treatment. Current proven approaches for insulin resistance—weight loss, exercise, and dietary changes—remain the best-established strategies. Confidence level: Moderate for the mechanism; Low for human application.
This research is most relevant to people with obesity and insulin resistance, people at risk for type 2 diabetes, and researchers developing new metabolic treatments. It’s less relevant to people with normal weight and healthy insulin sensitivity. Healthcare providers treating metabolic disorders should be aware of this mechanism but shouldn’t yet recommend liquiritigenin outside of clinical trials.
In the mouse studies, benefits appeared within the timeframe of the high-fat diet feeding (typically weeks to months in animal research). If liquiritigenin were developed into a human treatment, it would likely take 5-10 years of clinical trials before it could be prescribed. People shouldn’t expect immediate results; metabolic changes typically take weeks to months to become noticeable.
Frequently Asked Questions
Can I take licorice supplements to improve my insulin resistance?
Not yet based on this research. While liquiritigenin from licorice shows promise in mice, human studies haven’t been conducted. Licorice supplements can have side effects and interact with medications. Consult your doctor before trying any supplement for insulin resistance.
How does liquiritigenin help with obesity and blood sugar?
It reduces harmful molecules in immune cells living in fat tissue, preventing them from becoming inflamed and attacking fat cells. This allows fat cells to respond normally to insulin and take up glucose from the bloodstream more effectively.
Is this research ready to be used as a treatment for humans?
No. This is animal research showing the mechanism works in mice. Human clinical trials would be needed before liquiritigenin could be prescribed as a medication. This typically takes 5-10 years of testing.
What’s the difference between this compound and current diabetes medications?
Liquiritigenin targets immune cell dysfunction in fat tissue, a different mechanism than most current diabetes drugs. It’s a natural compound rather than synthetic, but natural doesn’t automatically mean safer—more research is needed.
Could this help prevent type 2 diabetes?
Possibly, based on this research showing it improves insulin sensitivity and glucose tolerance in obese mice. However, prevention studies in humans would be needed to confirm this benefit.
Want to Apply This Research?
- Track fasting blood glucose levels weekly and insulin sensitivity markers (like HbA1c) monthly if available through your healthcare provider, noting any dietary changes or supplements being tested
- Use the app to log consumption of licorice-containing foods or supplements (if pursuing this under medical supervision), correlating intake with blood sugar readings and energy levels to identify personal response patterns
- Create a 12-week tracking protocol measuring fasting glucose, post-meal glucose spikes, energy levels, and inflammation markers (if accessible), comparing baseline to post-intervention periods
This research is based on animal studies and has not been tested in humans. Liquiritigenin is not currently approved as a medical treatment. Do not use licorice supplements or liquiritigenin to treat insulin resistance, obesity, or diabetes without consulting your healthcare provider first. Licorice can interact with medications and cause side effects in some people. This article is for educational purposes only and should not replace professional medical advice. Anyone with metabolic disorders should work with their doctor on proven treatments including diet, exercise, and medications as appropriate.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.