Scientists discovered a protein in the brain called GPR75 that plays a major role in controlling how much we eat and how our body uses energy. Using specially designed mice, researchers found that when this protein was removed from brain cells, the mice ate less food and stayed thinner, even when eating a high-fat diet. This discovery suggests that targeting this brain protein could lead to new treatments for obesity. The findings are exciting because they show that obesity isn’t just about willpower—it’s also about how our brain chemistry controls hunger and metabolism.

The Quick Take

  • What they studied: How a brain protein called GPR75 controls eating habits and weight gain, and whether removing it could prevent obesity
  • Who participated: Specially bred laboratory mice with different versions of the GPR75 gene removed from their brains or fat tissue. The mice were fed high-fat diets to see how they would respond compared to normal mice
  • Key finding: Mice without the GPR75 protein in their brain cells ate significantly less food and gained much less weight on a high-fat diet compared to regular mice. They also burned slightly more calories, which helped them stay thinner
  • What it means for you: This research suggests that a brain-targeted medication blocking GPR75 might help people feel less hungry and maintain a healthier weight. However, this is early-stage research in mice, and it will take many more years of testing before any human treatments become available

The Research Details

Researchers created special laboratory mice where they could turn off the GPR75 gene in specific parts of the body. They made two main groups: one where the gene was removed only from brain cells, and another where it was removed only from fat cells. This allowed them to see which body part the protein was most important in. The mice were then fed a high-fat diet to see how they would gain weight compared to normal mice.

The scientists carefully measured how much the mice ate, how much energy they burned, and how much weight they gained over time. They also looked at the mice’s brain tissue and fat tissue under a microscope and studied which genes were turned on or off in different parts of their bodies.

This approach is powerful because it lets researchers understand exactly where in the body a protein does its job, rather than just knowing it matters somewhere. By comparing brain-specific changes to fat-specific changes, they could figure out that the brain is the most important location for GPR75’s role in weight control.

Understanding where and how GPR75 works is crucial for developing better obesity treatments. If scientists know the protein mainly works in the brain to control hunger, they can design medicines that specifically target the brain rather than affecting the whole body. This could mean fewer side effects and better results. The study also helps explain why some people struggle with weight—their GPR75 might be working differently than in others

This study was published in Science Advances, a highly respected scientific journal, which suggests the research met strict quality standards. The researchers used a well-designed approach by testing the protein in different body locations separately, which is more informative than just removing it everywhere. However, this is animal research in mice, not humans, so results may not directly apply to people. The study appears to be preliminary research that opens doors for future investigation rather than providing final answers

What the Results Show

When researchers removed GPR75 from brain cells, the mice showed dramatic protection against weight gain. These mice ate noticeably less food than normal mice, even when high-fat food was available. They also burned slightly more calories throughout the day. Together, these changes meant the mice stayed significantly thinner than control mice eating the same diet.

The brain regions where GPR75 was most active were those known to control hunger and energy use. When the protein was removed from these areas, the mice’s appetite signals appeared to change, making them feel less hungry. This is important because it shows the protein directly influences the brain’s hunger control center.

In contrast, when researchers removed GPR75 only from fat cells, there was almost no effect on overall weight gain or eating behavior. The fat cells did show some changes in how they used energy when exposed to cold, but this wasn’t enough to prevent obesity. This finding clearly showed that the brain, not the fat tissue, is where GPR75 matters most for weight control.

The study revealed that when mice ate a high-fat diet, their brains made more GPR75 protein, while their fat tissue made less. This pattern suggests the body tries to adapt to unhealthy eating by increasing this protein in the brain, but this adaptation may actually backfire by making people hungrier. Additionally, mice without GPR75 in their brains showed changes in how their livers stored fat, suggesting the brain protein affects metabolism throughout the entire body. Brown fat (a special type of fat that burns calories for heat) showed increased activity in mice without GPR75, which may contribute to their higher energy burning

Previous research in humans found that people with certain genetic changes in the GPR75 gene were more likely to be obese. This new study helps explain why—the protein appears to be a key controller of hunger in the brain. The findings align with other research showing that brain-based treatments for obesity may be more effective than treatments targeting fat tissue alone. This study builds on growing evidence that obesity is not simply a matter of eating too much, but involves complex brain chemistry that controls appetite and metabolism

This research was conducted in mice, not humans, so the results may not work exactly the same way in people. The study didn’t specify exactly how many mice were used in each experiment, making it harder to assess the strength of the findings. The research is preliminary and shows that removing the protein helps, but it doesn’t yet show whether blocking the protein with a medication would work the same way. Long-term effects in humans are unknown, and there could be side effects from blocking this protein that weren’t discovered in this mouse study

The Bottom Line

Based on this research, there is moderate evidence that brain-targeted treatments blocking GPR75 could help with obesity in the future. However, no such treatments currently exist for humans. If you’re struggling with weight, current evidence-based approaches like balanced nutrition, regular physical activity, and working with healthcare providers remain the best options. This research is exciting but represents early-stage science that needs many more years of development before human treatments become available

This research is most relevant to people struggling with obesity and those interested in understanding how the brain controls weight. It’s also important for pharmaceutical companies and researchers developing new obesity treatments. People with genetic variations in GPR75 might find this particularly interesting. However, this is not yet applicable to individual treatment decisions—it’s foundational science that will inform future medicine development

This is very early-stage research. Even if a medication targeting GPR75 were developed today, it would typically take 5-10 years of testing before it could be available to patients. Any benefits would likely develop gradually as the medication takes effect on brain hunger signals, probably over weeks to months rather than days

Want to Apply This Research?

  • Track daily hunger levels on a 1-10 scale and correlate with food intake patterns. Users can log when they feel hungry versus when they actually eat, helping identify whether hunger is driving eating behavior or if other factors are involved. This creates a personal baseline for understanding individual hunger patterns
  • Use the app to set realistic meal timing and practice eating only when genuinely hungry rather than out of habit or emotion. Users can set reminders to pause before eating and rate their hunger level, building awareness of true hunger signals versus automatic eating patterns
  • Over 4-8 weeks, track the relationship between reported hunger levels and actual food intake. Monitor weight trends alongside hunger ratings to see if reducing unnecessary eating (when not truly hungry) correlates with weight changes. This long-term tracking helps users understand their personal hunger-eating patterns and identify opportunities for improvement

This research is preliminary animal-based science and does not yet apply to human treatment or medical decisions. GPR75-targeting medications do not currently exist for human use. If you are struggling with weight or obesity, please consult with your healthcare provider about evidence-based treatment options including nutrition, exercise, and medical interventions. Do not make changes to your diet or health regimen based solely on this research. This article is for educational purposes only and should not be considered medical advice.