According to the researchers, the findings provide new clues about how tirzepatide works and could help guide the development of broader treatments for obesity and other metabolic disorders.

The research was led by Marion Peyrou, Ramón y Cajal researcher at the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), the Sant Joan de Déu Research Institute (IRSJD) and the CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN).

Tirzepatide Targets Two Hormone Receptors

Tirzepatide (generic name of the drug Mounjaro) is approved for weight management in adults with obesity or overweight with comorbidities, as well as for treating poorly controlled type 2 diabetes mellitus.

Unlike some other obesity medications, tirzepatide targets the receptors for two hormonal factors at the same time: GIP and GLP-1. This dual mechanism can produce substantial weight loss, largely because the drug reduces food intake.

Researchers wanted to determine whether tirzepatide also produces metabolic changes that cannot be explained simply by eating less.

To investigate, the team examined how the drug affected different fat deposits in an experimental mouse model, since this kind of detailed tissue analysis cannot readily be performed in humans. Obese mice — fed a high-fat diet — were treated with tirzepatide.

The researchers then compared those animals with mice that did not receive the drug but were given the same amount of food. By controlling food intake this way, the scientists could distinguish changes caused directly by tirzepatide from those resulting from reduced calorie consumption.

Mounjaro Activates Calorie-Burning Brown Fat

The analysis showed that tirzepatide activated brown adipose tissue. Unlike white adipose tissue, which primarily stores fat and tends to accumulate in obesity, brown fat specializes in using energy and ‘burning’ calories from food.

“This activation is associated with an increased capacity to burn metabolic energy and with the production of batokines by brown adipose tissue, molecules that are beneficial for metabolism,” says Marion Peyrou.

The finding suggests that tirzepatide may influence metabolism in ways that extend beyond the weight loss caused by appetite suppression and reduced food intake.

“This drug not only reduces body weight, but also has beneficial effects on metabolism. Active brown adipose tissue ‘burns’ glucose and fat within the body, which would contribute to its positive effect not only in reducing body weight, but also in lowering blood glucose and fat levels, and improving metabolism,” the researcher points out.

A Broader Strategy for Treating Obesity

Scientists have long viewed brown fat activation as a potentially useful strategy for treating obesity and other metabolic diseases. However, previous efforts to activate brown adipose tissue with drugs have often been unsuccessful because of unwanted side effects, particularly those affecting the heart.

“Tirzepatide, although it activates brown adipose tissue, does not have these negative effects; on the contrary, it shows cardiovascular benefits. If our findings are confirmed in humans, it would reinforce the importance of developing therapeutic strategies that not only reduce food intake but also increase energy expenditure and brown fat activation,” explains the researcher.

The results support the idea that obesity therapies may be more effective when they target several physiological processes at once instead of focusing only on appetite.

“This could help improve weight control and reduce associated disorders, such as type 2 diabetes and other metabolic disorders,” she adds.

Toward More Personalized Obesity Treatment

A clearer picture of how tirzepatide works could also influence how drugs in this class are prescribed in the future.

“Identifying which patient profiles could benefit most, for example those with more compromised energy expenditure, would open the door to more personalized medicine, based not only on appetite or weight control, but also on overall metabolic status,” she emphasizes.

The researchers caution, however, that the findings come from mice and cannot yet be assumed to apply in the same way to people. Human and mouse metabolism can differ substantially, as can the distribution of fat tissue and responses to medications.

“As this is a study conducted on mice, we must be cautious, as there may be significant differences between species in terms of metabolism regulation, adipose tissue distribution and response to drugs. Therefore, we need more clinical evidence on the action of these drugs on fat in humans,” concludes Peyrou.

Sleep offers a useful way to study that question. Although the body is resting, the brain remains active, especially during rapid eye movement (REM) sleep, which is closely associated with dreaming and memory processing. REM sleep is often described as “paradoxical sleep” because the body is mostly still while brain activity resembles wakefulness.

Researchers at Tohoku University have now identified another REM sleep paradox. During this stage, the apparent energy supply to the dreaming brain increases, yet levels of the energy molecule neurons directly use actually decline.

The findings were published in Communications Biology.

“Ever felt exhausted after a vivid dream?” asks Professor Ko Matsui of Tohoku University. “Sleep may appear peaceful, but the brain is highly active — especially when dreaming. We were intrigued by this paradox, and wanted to look into the scientific basis behind why dreaming is somehow tiring.”

Watching the Sleeping Brain in Real Time

To investigate what happens to brain energy during sleep, the researchers used a UV-curable resin to keep the skulls of mice transparent, allowing them to observe the brain during natural sleep.

Using wide-field fluorescence imaging, they tracked changes in brain blood volume as a sign of incoming “fuel” supply. They also measured neuronal ATP, the energy molecule that powers neurons, along with astrocytic pyruvate, a key compound that connects glucose from the blood with energy metabolism in the brain.

Non-REM sleep is well known for strong neuronal activity in the delta-band frequency, but smaller theta-band fluctuations also occur. The researchers found that these theta-band changes could predict shifts in brain blood volume several seconds later. That pattern suggests the sleeping brain adjusts its blood vessels in response to changing neuronal activity and metabolic demand.

The Brain Prepares for REM Sleep in Advance

A different pattern appeared as the brain moved from non-REM sleep into REM sleep.

About 50 seconds before the classically defined beginning of REM sleep, brain blood volume started to increase. The change began in the posterior cortex and then moved forward, pointing to a large-scale process that may prepare the brain metabolically for REM sleep.

Once REM sleep began, astrocytic pyruvate also rose. That increase was consistent with either greater availability of metabolic fuel or increased glycolytic activity in astrocytes.

But at the same time, neuronal ATP fell.

Why Does Neuronal Energy Drop During Dreams?

There are several possible explanations for this decrease in ATP.

Neurons may use large amounts of ATP during REM sleep to support memory-related synaptic reorganization, communication between the hippocampus and cortex, or broad transitions across brain circuits.

Another possibility is that the transfer of metabolic resources from astrocytes to neurons changes during REM sleep. Mitochondrial production of ATP could also shift during this stage.

Whatever the mechanism, the findings suggest that the dreaming brain may be operating under unusually high energy demands even while its fuel supply increases.

A Broader Lesson About the Brain’s Energy Economy

The results may also reveal something more fundamental about biological computation.

Unlike conventional computers, animal brains must operate within strict metabolic limits. Rather than supplying energy evenly across the brain, the nervous system may redirect resources depending on behavioral state, memory demands, and other internal needs.

“Understanding how the brain balances energy supply and consumption may help explain what makes biological intelligence so efficient,” explains lead investigator Yusuke Takahashi. “REM sleep gives us a natural example of how the brain reorganizes its energy economy to support complex internal processing.”

Sleep plays a critical role in functions such as memory consolidation and maintaining mental performance the following day. By revealing how energy supply and energy use shift during REM sleep, the research adds another piece to the puzzle of why sleep is so important not only for the body, but also for the brain.

Some of the most important are known as inner triplets. These groups of three quadrupole magnets (hence the name) sit on both sides of the LHC’s four main experiments. Their job is to focus the particle beams as tightly as possible just before the particles collide inside the detectors.

The tighter the beams are “compressed,” the greater the chance that particles will collide. That makes the inner triplets essential for increasing the LHC’s luminosity, i.e. the number of collisions that occur in a given period of time. More luminosity means more collisions, giving researchers more data to analyze.

Preparing the LHC for a New Era

A major part of the future High-Luminosity LHC (HiLumi LHC) project involves replacing the existing inner triplets with a much more powerful generation of magnets.

The work is taking place during the third long shutdown (LS3). Reently, crews cut the first magnet interconnection, formally beginning the replacement operation. CERN Director-General Mark Thomson also visited LHC Point 1 (the ATLAS experiment) to mark the milestone.

“The replacement of these magnets with the new HiLumi LHC inner triplets is crucial for the coming high-luminosity years. The first quadrupole of the new triplets should arrive in the tunnel at the start of 2029. In total, 16 cryostats and 28 cryo-assemblies will be installed – a major undertaking,” explains Jean-Philippe Tock, Head of the LS3 Coordination Team.

Magnets About 40% Stronger

The new inner triplets are the product of years of research and development. They represent a major technological advance over the niobium-titanium magnets currently operating inside the LHC.

Instead of niobium-titanium, the upgraded magnets use niobium-tin superconducting coils. This allows them to generate magnetic fields reaching 11.3 tesla, about 40% stronger than the fields produced by the current magnets.

The new equipment will be installed around the ATLAS and CMS experiments, where the increased collision rate will be especially important.

ALICE and LHCb operate differently and pursue different physics programs, so they do not need the same increase in instantaneous luminosity. Their existing inner triplets can therefore remain in place. However, those magnets will still be upgraded so that both experiments can benefit from the overall increase in luminosity.

Removing 28 Superconducting Magnets

Since September 7, CERN teams have been dismantling sections of the collider on either side of ATLAS and CMS. The goal is to remove 28 superconducting magnets (including the inner triplets) that are scheduled to be replaced.

The operation marks the end of an era for hardware that has been part of the LHC since its construction.

“Today’s event is a major milestone for CERN, especially for the HiLumi LHC project team. The current inner triplets date back to the LHC construction phase and were installed in the machine between 2005 and 2007. After nearly twenty years of operation, they will give way to a new generation of even more powerful magnets. It’s truly remarkable to witness such a handover from one generation of innovation to the next,” says Markus Zerlauth, the HiLumi LHC Project Leader.

The discovery, reported in Science Advances, shows a subduction zone actively breaking into pieces. Subduction zones form where one tectonic plate is forced beneath another and pushed deep into Earth. They are responsible for some of the planet’s largest earthquakes, powerful volcanic eruptions, and long term changes to continents and ocean basins.

Until now, however, scientists have had few opportunities to see clearly how one of these enormous systems reaches the end of its life.

How a Subduction Zone Dies

Subduction is one of the main processes that continually reshapes Earth’s surface. As an oceanic plate sinks beneath another plate, material from the crust is carried downward toward the mantle, the hot layer beneath Earth’s crust.

These systems can remain active for millions of years, but they cannot continue indefinitely. Otherwise, continents would eventually pile into one another, oceans would disappear, and much of Earth’s geological history would be erased.

That leaves geologists with a fundamental question: what actually causes a mature subduction zone to stop?

“Getting a subduction zone started is like trying to push a train uphill — it takes a huge effort,” said Brandon Shuck, a geologist at Louisiana State University and lead author of the study. “But once it’s moving, it’s like the train is racing downhill, impossible to stop. Ending it requires something dramatic — basically, a train wreck.”

Scientists may now be watching that process unfold beneath Cascadia.

A Tectonic Plate Breaking Apart Beneath Cascadia

Off Vancouver Island, the Juan de Fuca and Explorer plates are slowly being forced beneath the North American plate. This area is part of the Cascadia subduction zone, a vast tectonic boundary stretching along the Pacific Northwest.

Researchers combined detailed earthquake records with seismic reflection imaging to look deep beneath the seafloor. The technique works somewhat like medical ultrasound. Scientists send sound waves into Earth and measure how those waves bounce back from different underground structures.

The seismic measurements came from the NSF funded 2021 Cascadia Seismic Imaging Experiment (CASIE21), during which researchers aboard a ship sent sound waves into the ocean floor. A 15-kilometer-long streamer carrying underwater listening instruments recorded the returning signals.

By analyzing those echoes, scientists created detailed images of structures hidden beneath the seafloor. What emerged was striking: large faults and fractures cutting through the sinking plate, including areas where the plate appears to be actively snapping apart.

“This is the first time we have a clear picture of a subduction zone caught in the act of dying,” said Shuck. “Rather than shutting down all at once, the plate is ripping apart piece by piece, creating smaller microplates and new boundaries. So instead of a big train wreck, it’s like watching a train slowly derail, one car at a time.”

A 75 Kilometer Tear Through the Plate

The researchers identified several tears running through the oceanic plate. One especially dramatic feature involves an enormous offset where part of the slab has dropped by roughly five kilometers.

“There’s a very large fault that’s actively breaking the plate,” Shuck explained. “It’s not 100% torn off yet, but it’s close.”

Earthquake activity provides another clue about what is happening.

Along a tear stretching about 75 kilometers, some portions continue to produce earthquakes while others have become unusually quiet. That difference matters because earthquakes occur when connected blocks of rock build up stress and suddenly slip.

“Once a piece has completely broken off, it no longer produces earthquakes because the rocks aren’t stuck together anymore,” he said.

The absence of earthquakes along part of the tear therefore suggests that a section of the plate has already separated. According to the researchers, that detached area is gradually expanding.

Earth’s Crust May Break Apart Piece by Piece

Rather than failing in one enormous event, the subduction zone appears to be shutting down through a series of smaller breakups.

Researchers describe the process as “episodic” or “piecewise” termination. Individual sections tear away at different times, slowly dismantling the larger tectonic system.

Transform boundaries play an important role. These are faults where sections of Earth’s crust move sideways past one another. In this setting, they can act almost like geological scissors, cutting across the plate and helping isolate individual fragments.

Once a piece becomes separated, it can form a microplate. A microplate is essentially a smaller piece of Earth’s rigid outer shell that moves somewhat independently from the major tectonic plates surrounding it.

Meanwhile, nearby portions of the larger plate can continue sinking.

As more pieces detach, the remaining plate loses some of the downward pull that keeps subduction going. Shuck compares the process to removing cars from a runaway train. Eventually, there is not enough of the system left to continue in the same way.

The breakup of each individual section can take several million years. Together, however, these episodes can eventually bring an entire subduction zone to an end.

Ancient Tectonic Mysteries Begin to Make Sense

The discovery may help explain geological puzzles seen in other parts of the world.

Scientists have found abandoned plate fragments and unusual sequences of volcanic rocks that appear to record the final stages of ancient subduction systems. Until now, researchers had evidence that these systems had broken apart, but much less direct information about how the process unfolded.

One important example can be found off Baja California.

There, geologists have identified fossil microplates left behind by the Farallon plate, an enormous ancient oceanic plate that once extended across a large portion of the eastern Pacific.

Those fragments have long suggested that the Farallon plate did not simply disappear in one event. The Cascadia observations now offer a possible explanation for how such remnants form.

Instead of collapsing all at once, a dying subduction zone may gradually unravel, leaving smaller plate fragments scattered behind as geological evidence.

Tearing Plates Could Trigger Volcanic Changes

The breakup can also change what happens deeper beneath Earth’s surface.

When a piece of a sinking plate separates, an opening called a “slab window” can form. This gap allows hotter material from the mantle to rise toward the surface.

That rising material can alter magma production and potentially contribute to episodes of volcanic activity.

As the breakup continues, tectonic boundaries can shift, additional microplates can form, and different parts of the subduction system may shut down at different times.

“It’s a progressive breakdown, one episode at a time,” said Shuck. “And it matches really well with what we see in the geologic record, where volcanic rocks get younger or older in a sequence that reflects this step-by-step tearing.”

That connection between modern observations and ancient rocks gives researchers a new way to interpret the remains of long vanished plate boundaries.

What This Means for Cascadia Earthquakes

The findings also raise an important question for the Pacific Northwest: could these newly identified tears affect future earthquakes?

Researchers now want to understand whether a large earthquake could continue rupturing across one of the breaks or whether the damaged sections of the plate might alter the path of a rupture.

A rupture is the rapid movement along a fault that produces an earthquake. The distance a rupture travels, and the structures it encounters along the way, can strongly influence the size and behavior of an earthquake.

For now, the researchers emphasize that the discovery does not significantly change Cascadia’s earthquake hazard on a human timescale.

The region is still capable of producing extremely large earthquakes and tsunamis. The breakup observed beneath the ocean is unfolding over millions of years, not decades or centuries.

However, adding these newly discovered structures to earthquake models could eventually improve scientists’ understanding of how future ruptures may behave.

For geologists, Cascadia is offering something even rarer: a chance to watch one of Earth’s great tectonic systems slowly dismantle itself, one piece at a time.

The discovery is puzzling because, based on known mechanisms, this small stellar remnant should not be capable of producing the structure seen around it. The unexpected finding challenges current ideas about how dead stars exchange matter and energy with their surroundings.

“We found something never seen before and, more importantly, entirely unexpected,” says Simone Scaringi, associate professor at Durham University, UK and co-lead author of the study published in Nature Astronomy.

“Our observations reveal a powerful outflow that, according to our current understanding, shouldn’t be there,” says Krystian Ilkiewicz, a postdoctoral researcher at the Nicolaus Copernicus Astronomical Center in Warsaw, Poland and study co-lead.

Astronomers use the term ‘outflow’ to describe material expelled from an object in space.

A Shock Wave Around a Dead Star

RXJ0528+2838 lies about 730 light-years from Earth. Like the Sun and other stars, it travels around the center of the Milky Way. As it moves through space, it encounters gas between the stars, producing a type of shock wave known as a bow shock.

Noel Castro Segura, research fellow at the University of Warwick in the UK and collaborator in this study, describes it as “a curved arc of material, similar to the wave that builds up in front of a ship.”

Bow shocks are typically produced when material flowing away from a star slams into its surroundings. In the case of RXJ0528+2838, however, astronomers cannot identify any known process that fully accounts for what they observed.

A White Dwarf With No Disk

RXJ0528+2838 is a white dwarf, the leftover core of a dying low-mass star, and it is orbited by a Sun-like companion.

In binary systems like this one, material can be pulled away from the companion and transferred onto the white dwarf. That material often forms a disc around the dead star. The disc feeds the white dwarf, while some matter can also be thrown back into space in powerful outflows.

RXJ0528+2838 is different. Astronomers see no evidence of such a disc, leaving them without the usual explanation for the outflow and the surrounding nebula.

“The surprise that a supposedly quiet, discless system could drive such a spectacular nebula was one of those rare ‘wow’ moments,” says Scaringi.

VLT Observations Confirm the Source

The unusual structure was first noticed in images taken with the Isaac Newton Telescope in Spain. Its strange appearance prompted the researchers to investigate it more closely using the MUSE instrument on ESO’s VLT.

“Observations with the ESO MUSE instrument allowed us to map the bow shock in detail and analyse its composition. This was crucial to confirm that the structure really originates from the binary system and not from an unrelated nebula or interstellar cloud,” Ilkiewicz explains.

The bow shock’s size and shape suggest that RXJ0528+2838 has been producing a powerful outflow for at least 1000 years.

That creates another problem. Scientists do not yet know how a dead star without a disc could sustain such an outflow for so long, although the system’s magnetic field may provide an important clue.

A Magnetic Field May Hold Part of the Answer

RXJ0528+2838 is known to possess a strong magnetic field, something the MUSE observations also confirmed.

Instead of allowing material from the companion star to settle into a disc, the magnetic field appears to guide that matter directly onto the white dwarf.

“Our finding shows that even without a disc, these systems can drive powerful outflows, revealing a mechanism we do not yet understand. This discovery challenges the standard picture of how matter moves and interacts in these extreme binary systems,” Ilkiewicz explains.

The researchers suspect that the magnetic field could be connected to a hidden source of energy, which Scaringi describes as a ‘mystery engine.’ But the explanation remains incomplete.

According to the observations, the white dwarf’s present-day magnetic field could sustain a bow shock for only a few hundred years. The structure appears to have existed for at least 1000 years, meaning the magnetic field alone cannot yet explain the full phenomenon.

Searching for the “Mystery Engine”

Astronomers will need to investigate many more binary systems to determine how these powerful outflows can form without discs.

ESO’s upcoming Extremely Large Telescope (ELT) could play an important role by allowing scientists to study both known systems and much fainter examples in greater detail.

Scaringi expects the telescope “to map more of these systems as well as fainter ones and detect similar systems in detail, ultimately helping in understanding the mysterious energy source that remains unexplained.”