When mice are exposed to cold temperatures, their bodies need more energy and they eat more food. Scientists discovered that their intestines actually grow larger to absorb more nutrients from the extra food they eat. This study found that two special hormone signals in the gut—called GLP-1 and GLP-2—are necessary for the intestines to expand when exposed to cold. Without the GLP-2 signal specifically, the intestines couldn’t grow properly even though the mice ate more. This research helps us understand how our bodies adapt to environmental stress and could eventually explain similar processes in humans.

The Quick Take

  • What they studied: Whether special gut hormones called GLP-1 and GLP-2 are needed for the intestines to grow bigger when exposed to cold temperatures
  • Who participated: Laboratory mice of both sexes, including normal mice and genetically modified mice missing certain hormone receptors, exposed to either cold (6°C) or warm (27°C) conditions for five weeks
  • Key finding: The GLP-2 hormone signal is essential for the small intestine to expand its absorptive surface when exposed to cold stress. Mice without this signal couldn’t grow their intestines properly, even though they ate significantly more food in the cold
  • What it means for you: This suggests that our bodies have built-in systems to adapt to environmental stress by changing how our digestive system works. Understanding these systems may eventually help treat digestive problems or metabolic disorders, though more research in humans is needed

The Research Details

Researchers studied three groups of mice: normal mice, mice missing two hormone receptors (GLP-1 and GIP), and mice missing two different hormone receptors (GLP-1 and GLP-2). They placed these mice in either cold conditions (6°C, similar to a refrigerator) or warm, comfortable conditions (27°C) for five weeks. They measured how much food the mice ate, how much their intestines grew, and how much weight they gained. They also measured hormone levels in the blood to understand what was happening inside their bodies.

This research design is important because it uses genetic tools to turn off specific hormone signals one at a time. This allows scientists to figure out which hormone signals are actually responsible for the intestinal changes, rather than just observing that changes happen. By comparing normal mice to genetically modified mice, researchers can identify the exact biological mechanisms at work

This is a controlled laboratory study published in a peer-reviewed scientific journal, which means other experts reviewed the work before publication. The researchers tested both male and female mice, which strengthens the findings. However, because this was done in mice rather than humans, the results may not directly apply to people. The study was well-designed with clear comparisons between different groups

What the Results Show

All three groups of mice—normal, DIRKO, and GLPDRKO—ate significantly more food when exposed to cold compared to warm conditions. This makes sense because their bodies needed extra energy to stay warm. However, the intestinal changes were very different between groups. In normal mice and DIRKO mice (missing GLP-1 and GIP signals), the small intestine grew larger in cold conditions, with longer finger-like projections (villi) and deeper pockets (crypts) that increase the surface area for absorbing nutrients. These structural changes did not occur in GLPDRKO mice (missing GLP-1 and GLP-2 signals), even though they ate just as much food as the other groups in the cold. This tells us that the GLP-2 hormone signal is specifically required for the intestine to expand.

An important secondary finding was that GLPDRKO mice failed to gain body weight over the five-week experiment, while normal mice gained weight normally. This suggests that even though these mice ate more food, without the GLP-2 signal allowing their intestines to grow, they couldn’t absorb enough nutrients to support weight gain. Interestingly, DIRKO mice (which still had GLP-2 signaling) did gain weight normally despite lacking GLP-1 and GIP signals, suggesting that GLP-2 signaling alone may be sufficient for weight gain under cold stress. Blood tests also showed that GLP-1 hormone levels were significantly elevated in GLPDRKO mice, indicating that the body was producing extra GLP-1 to try to compensate for the missing GLP-2 signal, but this compensation wasn’t enough

Previous research has shown that gut hormones like GLP-1 and GLP-2 are important for digestion and nutrient absorption under normal conditions. This study extends that knowledge by showing these hormones are also critical for how the gut adapts to environmental stress like cold exposure. The finding that GLP-2 is specifically required for intestinal growth during stress is new and helps explain how our bodies coordinate increased food intake with increased digestive capacity. This builds on earlier work showing that the intestines can physically adapt to changing nutritional demands

This study was conducted entirely in laboratory mice, so we cannot be certain the same mechanisms work in humans. The study lasted only five weeks, so we don’t know if these changes would continue, reverse, or change further over longer periods. The researchers didn’t measure all possible hormone signals that might be involved, so other factors could also play a role. Additionally, the study focused on acute cold exposure in controlled laboratory settings, which may not fully represent how human bodies respond to natural cold exposure or gradual temperature changes. The study also didn’t examine whether these intestinal changes have any negative effects or whether they reverse when mice return to warm conditions

The Bottom Line

Based on this research, there are no direct recommendations for human behavior yet, as this is early-stage animal research. However, it suggests that people exposed to chronic cold stress may experience changes in their digestive systems and nutrient absorption. If you live in a cold climate or are frequently exposed to cold, maintaining good nutrition and staying warm may help support normal digestive function. This research may eventually lead to treatments for people with digestive disorders or metabolic problems, but more human studies are needed first. (Confidence level: Low for human application; High for understanding the biological mechanism)

This research is most relevant to scientists studying digestion, metabolism, and how bodies adapt to stress. It may eventually matter to people with digestive disorders, metabolic diseases, or those living in extremely cold climates. It’s less immediately relevant to people living in temperate climates or those without digestive issues. Healthcare providers treating patients with GLP-1 or GLP-2 receptor-related conditions may find this information useful for understanding how these hormones work

In mice, the intestinal changes occurred over five weeks of continuous cold exposure. If similar processes occur in humans, changes would likely take weeks to months to develop. However, we don’t yet know if humans would show the same adaptations or on what timeline. Any potential health benefits or applications would likely take years of additional research to develop and test in human populations

Want to Apply This Research?

  • Track daily food intake and digestive symptoms (bloating, energy levels, appetite) during cold weather months versus warm months to identify personal patterns in how temperature affects hunger and digestion
  • Use the app to set reminders to maintain consistent meal timing and nutrition during winter months or cold exposure periods, and monitor whether digestive comfort changes with temperature or seasonal variations
  • Create a seasonal comparison log tracking appetite, food intake, energy levels, and digestive comfort across different seasons and temperature exposures over 3-6 months to identify personal metabolic patterns

This research was conducted in laboratory mice and has not been tested in humans. The findings do not yet have direct clinical applications for human health. If you have concerns about your digestive health, nutrient absorption, or metabolic function, especially related to cold exposure or seasonal changes, consult with a healthcare provider. Do not make changes to your diet or medical treatment based solely on this animal research. Anyone taking GLP-1 or GLP-2 receptor medications should discuss this research with their doctor, as it may provide context for understanding how these medications work, but should not influence medication use without medical guidance.