Geologists have now discovered that the earthquake began almost simultaneously at two different points on the fault, allowing the seismic rupture to encircle and break through a resistant area on the fault known as a barrier. This rare “dual-initiation” mechanism applied intense pressure from both sides of the barrier, leading to the powerful release of energy and substantial ground shaking across the Noto Peninsula.

The Noto earthquake was preceded by intense seismic swarms, which are sequences of many small earthquakes that can sometimes lead to a larger, catastrophic event. By using advanced seismic and geodetic technologies, the research team meticulously analyzed the movements within the Earth during this swarm that led to the earthquake.

The study, published in the journal Science, offers insight into the role of fault barriers, also known as asperities, in earthquake genesis, and will help improve seismic risk assessments and future earthquake forecasting.

Earthquakes happen when fractures in the Earth’s crust, known as faults, allow blocks of rocks on either side of the fault to move past each other. This movement is localized, not continuous along the fault line, because the line is not even or smooth, which dissipates energy and eventually stops the movement.

A barrier is a rough area that locks the two sides of a fault in place. Barriers absorb the energy of fault movement, slowing it down or stopping it altogether. But there’s only so much energy the barrier can absorb, and under the right conditions, the pent-up energy causes it to break violently, leading to strong shaking. A swarm of small earthquakes might not be enough to break a barrier, but if much stronger subsequent movement occurs on the fault, the barrier’s rupture will release all that stored-up energy.

Led by Lingsen Meng, a UCLA associate professor of earth, planetary and space sciences, UCLA graduate student Liuwei Xu and UC Santa Barbara geophysics professor Chen Ji, an international team of researchers from the United States, France, China and Japan analyzed geospatial data and recordings of seismic waves to understand the relationships between the swarm of smaller tremors and the larger earthquake that followed them. They identified a previously unknown barrier in the region of the swarm.

To their surprise, the New Year’s Day earthquake began almost simultaneously in two separate locations on the fault. Energy from each location moved toward the barrier, causing a violent rupture and extremely strong shaking.

“The earthquake started in two places and circled together,” Meng said. “The first one started waves that traveled fast and triggered a different epicenter. Then both parts propagated outward together and met in middle, where the barrier was, and broke it.”

The mechanics resemble bending a pencil on both ends until it snaps in the middle.

The finding was surprising because although dual initiation, as the process is known, has been seen in simulations, it has been much harder to observe in nature. Dual-initiation mechanisms require just the right conditions, which can be set in the lab but are less predictable in the real world.

“We were able to observe it because Japan has very good seismic monitoring stations and we also used GPS and satellite radar data. We grabbed all the data we could find! It’s only through all of this data together that we got really good resolution on this fault and could get into these fine details,” Meng said.

The vast majority of earthquakes don’t have anywhere near this level of data collected, so it’s possible that earthquakes with dual-initiation mechanisms are more common than geologists think.

“It could be that through better imaging and resolution, we’ll identify more like this in the future,” Meng said.

Earthquakes with dual epicenters have a higher risk for stronger shaking because there is stronger movement. Meng’s group plans to consider future scenarios to learn about the conditions and probabilities of these earthquakes.

“Our findings emphasize the complex nature of earthquake initiation and the critical conditions that can lead to large-scale seismic events,” Meng said. “Understanding these processes is vital for improving our ability to predict and mitigate the impacts of future earthquakes.”

Key takeaways

• The 7.5- magnitude earthquake beneath Japan’s Noto Peninsula on Jan. 1, 2024, occurred when a “dual-initiation mechanism” applied enough energy from two different locations to break through a fault barrier — an area that locks two sides of a fault in place and absorbs the energy of fault movement, slowing it down or stopping it altogether.
• An international team of researchers led by UCLA graduate student Liuwei Xu, professor Lingsen Meng and UC Santa Barbara’s Chen Ji analyzed a preceding seismic swarm and identified a previously unknown barrier in the region of the swarm.
• The team’s data collection methods could aid future research into the conditions and probabilities of dual-initiation earthquakes.

But a unique experiment led by Peter Reich of the University of Michigan is showing that, on a warming planet, more carbon is escaping the soil than is being added by plants.

“This is not good news because it suggests that, as the world warms, soils are going to give back some of their carbon to the atmosphere,” said Reich, director of the Institute for Global Change Biology at U-M.

“The big picture story is that losing more carbon is always going to be a bad thing for climate,” said Guopeng Liang, the lead author of the study published in Nature Geoscience. Liang was a postdoctoral researcher at the University of Minnesota during the study and is now a postdoctoral researcher at Yale University and an exchange fellow at the Institute for Global Change Biology.

By understanding how rising temperatures affect the flow of carbon into and out of soils, scientists can better understand and forecast changes in our planet’s climate. Forests, for their part, store roughly 40% of the Earth’s soil carbon.

Because of that, there have been many research projects studying how climate change affects the carbon flux from forest soils. But few have lasted for longer than three years and most look at warming either in the soil or in air above it, but not both, Reich said.

In the experiment believed to be the first of its kind led by Reich, researchers controlled both the soil and above-ground temperatures in open air, without the use of any kind of enclosure. They also kept the study running for more than a dozen years.

“Our experiment is unique,” said Reich, who is also a professor at the U-M School for Environment and Sustainability. “It’s far and away the most realistic experiment like this in the world.”

The trade-off is that running such a sophisticated experiment for so long is expensive. The research was supported by the National Science Foundation, the U.S. Department of Energy and the University of Minnesota, where Reich is also a Distinguished McKnight University Professor.

Joining Reich and Liang on the study were colleagues from the University of Minnesota, the University of Illinois and the Smithsonian Environmental Research Center.

The team worked at two sites in northern Minnesota on a total of 72 plots, investigating two different warming scenarios compared with ambient conditions.

In one, plots were kept at 1.7 degrees Celsius above ambient and, in the other, the difference was 3.3 degrees Celsius (or about 3 and 6 degrees Fahrenheit, respectively). Soil respiration — the process that releases carbon dioxide — increased by 7% in the more modest warming case and by 17% in the more extreme case.

The respired carbon comes from the metabolism of plant roots and of soil microbes feeding on carbon-containing snacks available to them: sugars and starches leached out of roots, dead and decaying plant parts, soil organic matter, and other live and dead microorganisms.

“The microbes are a lot like us. Some of what we eat is respired back to the atmosphere,” Reich said. “They use the same exact metabolic process we do to breathe CO2 back out into the air.”

Although the amount of respired carbon dioxide increased in plots at higher temperatures, it likely didn’t jump as much as it could have, the researchers found.

Their experimental setup also accounted for soil moisture, which decreased at warmer temperatures that cause faster water loss from plants and soils. Microbes, however, prefer wetter soils and the drier soils constrained respiration.

“The take-home message here is that forests are going to lose more carbon than we would like,” Reich said. “But maybe not as they would if this drying wasn’t happening.”

Rice University bioengineers report harnessing the lotus effect to develop a system for culturing cancer cell clusters that can shed light on hard-to-study tumor properties. The new zinc oxide-based culturing surface mimics the lotus leaf surface structure, providing a highly tunable platform for the high-throughput generation of three-dimensional nanoscale tumor models.

The superhydrophobic array device (SHArD) designed by Rice bioengineer Michael King and collaborators can be used to create tunable, compact, physiologically relevant models for studying the progression of cancer, including metastasis — the stage in the disease when cancerous cells travel through the bloodstream from a primary tumor site to other parts of the body.

“The study of metastasis — the leading cause of cancer deaths — poses a particular challenge in part due to the difficulty of developing accurate, high-throughput models,” said King, who is corresponding author on a study published in ACS Nano that describes the new culturing platform. “We hope this tool will unlock new knowledge about this problematic stage of the disease and help us identify ways to intervene in order to stop or prevent it from happening.”

Scientists and clinicians now rely on blood samples containing circulating tumor cells — a key marker of metastasis — to understand the properties of primary tumors as well as what causes cancer to spread. Often referred to as “liquid biopsy,” this sampling approach typically does not yield enough of a “catch” to enable in-depth, large-scale studies of metastatic processes.

“‘Safety in numbers’ unfortunately also applies to cancer cells circulating in the bloodstream,” said Alexandria Carter, a researcher in the King lab who is a co-author on the study. “Cancer cells traveling alone are more likely to succumb to shear stress destruction or immune cell attacks. However, when they travel in groups, the likelihood that they successfully reach and settle in other parts of the body increases.

“Those few lone cancer cells in a single blood draw are already rare, so isolating enough clusters for a detailed study is especially challenging. This is why SHArD is an exciting new tool for understanding primary and metastatic cancer.”

The King lab had previously succeeded in creating nanorod layers of halloysite, a naturally occurring substance whose texture promotes the adhesion of circulating tumor cells while simultaneously repelling blood cells.

“When Kalana Jayawardana joined our lab as a new postdoctoral fellow in 2018, he started to experiment with growing zinc oxide nanorod surfaces,” said King, a Cancer Prevention and Research Institute of Texas Scholar who recently joined Rice as the E.D. Butcher Chair of Bioengineering and special adviser to the provost on life science collaborations with the Texas Medical Center. “At first, we didn’t have a specific application in mind, but we were curious and hopeful that the new material would have special properties that would be useful for cancer biology.”

The project was later taken over by a doctoral student in the King lab, Maria Lopez-Cavestany, and took off in an exciting direction. Cavestany, now a Ph.D. graduate, is the first author on the study.

Once they were able to grow a stable “carpet” of zinc oxide nanotubes, the researchers added a teflonlike coating on top, in essence recreating the lotus leaf structure — nanoscale roughness combined with a hydrophobic layer that together gave rise to true superhydrophobicity, a word stemming from the Greek for “extreme fear of water.” To create SHArD, the researchers added a microwell grid with perfectly sized compartments, then tested the system to assess its performance.

“SHArD is ready to use in biomedical research,” Carter said. “Any lab with clean room access can follow our protocols and create versions of this platform that meet the exact needs of their specific research projects.”

Initially intended as a means to reliably culture primary tumor models at a higher throughput, SHArD is highly tunable and can easily be adapted to culture metastatic clusters as well. The fact that SHArD was successfully used to grow spheroidal models of primary tumors already expands the cancer modeling toolkit, making it possible to create superhydrophobic culturing devices in the absence of highly specialized equipment.

“The cluster-forming device has opened the door to new areas of research into the dangerous clusters found in the bloodstream of late-stage cancer patients,” King said.

The study published this week in The Journal of Clinical Endocrinology & Metabolism.

“This study builds support for the importance of good sleep habits,” said lead author Brooke Shafer, Ph.D., a postdoctoral researcher in the Sleep, Chronobiology and Health Laboratory in the OHSU School of Nursing. “Sleep practices, like going to bed when you’re tired or setting aside your screen at night, can help to promote good overall health.”

The study recruited 30 people, split evenly between men and women. All had a body mass index above 25, which put them into an overweight or obese category.

“Obesity and cardiometabolic disease are growing public health concerns,” Shafer said. “Our research shows that disruptions in the body’s internal biological clock could contribute to negative health consequences for people who may already be vulnerable due to weight.”

Generally healthy participants contributed a saliva sample every 30 minutes until late in the night at a sleep lab on OHSU’s Marquam Hill campus to determine the time at which their body started naturally producing the hormone melatonin. Melatonin is generally understood to begin the process of falling asleep, and its onset varies with an individual’s internal biological clock.

Participants then went home and logged their sleep habits over the following seven days.

Researchers assessed the time difference between melatonin onset and average sleep timing for each participant, categorizing them into two groups: those who had a narrow window, with a short time duration between melatonin onset and sleep, and those with a wide window, with a longer duration between melatonin onset and sleep. A narrow window suggests someone who is staying awake too late for their internal body clock and is generally associated with poorer health outcomes.

The new study confirmed a variety of potentially harmful health measures in the group that went to sleep closer to melatonin onset.

It also found key differences between men and women. Men in this group had higher levels of belly fat and fatty triglycerides in the blood, and higher overall metabolic syndrome risk scores than the men who slept better. Women in this group had higher overall body fat percentage, glucose and resting heart rates.

“It was really somewhat surprising to see these differences present themselves in a sex-dependent manner,” said senior author Andrew McHill, Ph.D., assistant professor in the OHSU School of Nursing, the School of Medicine and the Oregon Institute of Occupational Health Sciences at OHSU. “It’s not one size fits all, as we sometimes think in academic medicine.”

The next phase of research will determine sex-specific differences in groups that experience more severe changes in sleep patterns, such as workers pulling overnight shifts.

“We want to figure out possible interventions that keep this vital core group of the workforce healthy,” Shafer said.

This work was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health, awards T32HL083808, K01HL146992, R01HL105495, R35HL155681; and the National Center For Advancing Translational Sciences of the NIH, awards UL1TR000128, UL1TR002369 ; and by the Oregon Institute of Occupational Health Sciences at OHSU via funds from the Division of Consumer and Business Services of the state of Oregon (ORS 656.630). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The fetus’s stool, called the “meconium,” is sterile but nevertheless causes inflammation of the abdominal cavity when it leaks out of the intestine after a perforation. Called “meconium peritonitis,” this is a life-threatening condition for the baby with a mortality rate of 10%-15% in humans, and neither a cause nor a treatment have been established.

The Kobe University pediatrician FUJIOKA Kazumichi and his team therefore decided to replicate the condition in mice. Since the intestinal development of mice and humans is different, the intestine of a newborn mouse pup is equivalent to that of a human fetus after the 12th week of pregnancy, but even so, the mouse pup is too small and fragile to induce the condition through an operation. The research team therefore created a slurry of meconium, which they took from human newborns, and injected it into the abdominal cavity of the pups. They then characterized the resulting condition and compared the pups’ mortality rates in response to different treatments.

Their results, published in the journal Pediatric Research, show that mortality was not influenced by antibiotic treatment, ruling out a bacterial cause. However, when they heat-treated the meconium slurry before injection, which disrupts the natural shapes of proteins, they found a significant reduction in mortality. This indicates that proteins contained in the meconium are responsible for the inflammation and in particular the researchers assume digestive enzymes that are abundant in the meconium to be the culprits.

The Kobe University development has more general implications, too. In a different set of experiments, Fujioka and his team characterized the condition of the mice pups after the meconium slurry administration by analyzing the mice’s biochemical and gene expression profiles. Comparing that to the results of a previously established mouse model, where the pups were injected an extract of intestinal contents of adult mice, they could show that their model results in different symptoms. Believing that their model is thus likely to be specific to meconium-caused inflammation, the researchers argue that it is an apt platform to conduct more research on the condition.

Fujioka and his team hope that their work will enable the search for an effective treatment of the condition, which occurs in about one out of every 35,000 live births. They conclude their paper saying, “As our mouse model is simple and highly reproducible, it can be used in research to elucidate the pathophysiology of meconium peritonitis.”

This research was funded by the Japan Society for the Promotion of Science (grants 18K15710 and 20K08229), the Morinaga Hoshi-kai Foundation, the Kawano Masanori Memorial Public Interest Incorporated Foundation for the Promotion of Pediatrics and the Japan Foundation for Pediatric Research.

“When your senses decline, you can’t experience the world as well,” said Jayant Pinto, MD, a physician and expert in olfactory dysfunction at UChicago Medicine. “You can’t hear colleagues or friends at the dinner table; you can’t discern what’s going on in your environment; you may have a hard time reading or making things out when you’re in your neighborhood. It makes all your cognitive burdens a little harder, and that probably wears you down over time and causes mental health problems.”

Along with Alexander Wang, a medical student at the UChicago Pritzker School of Medicine, Pinto recently led a study examining the prevalence and impact of sensory impairments among older adults. They found that people with sensory disabilities tend to have worse mental health, and that different types of sensory disability were associated with different aspects of mental health.

Revealing associations between perception and emotion

The UChicago researchers analyzed data on sensory function (vision, hearing and sense of smell) and self-reported mental health from nearly 4,000 older adults, collected over 10 years of follow-up as part of the National Social Life, Health & Aging Project. They found that people who had multiple senses impaired experienced more loneliness and had significantly worse self-reported mental health overall, and people with three sensory disabilities were more likely to experience frequent depressive episodes. In analyses that differentiated between the senses, vision impairment was most strongly associated with both loneliness and poor self-rated mental health.

Scientists are still exploring how changes in all five senses can impact people, but the UChicago researchers can already point to many ways sensory decline contributes directly to feelings of loneliness, sadness and boredom.

Older people with vision impairment may have trouble getting out of the house or seeing the faces of their friends and family, and hearing loss can make conversations stilted and frustrating. Even loss of smell can affect someone’s ability to find joy in familiar scents — like a favorite home-cooked meal or a loved one’s signature perfume — and perceive pheromones, which (though not registered consciously) contribute to social dynamics.

“We saw that hearing and vision disability tended to be associated with lower self-rated mental health and feelings of loneliness, but olfactory disability had a weaker association,” Wang said. “This stood out to me because hearing and vision disabilities tend to be much more stigmatized than olfactory disability. This made me reflect on the ways in which social stigma may be driving this worse mental health.”

Caring for one another in an aging society

In the face of that stigma, the researchers say their results highlight the importance of improving access to mental health services and increasing awareness of the connection between sensory loss and mental distress. In particular, understanding how different sensory disabilities impact the long-term mental health of older adults could help healthcare professionals — especially primary care providers, otolaryngologists and ophthalmologists — screen for mental health conditions when they identify sensory loss in their patients, providing opportunities for personalized and timely interventions.

In addition to proactively treating older adults’ mental health, the researchers pointed to steps that can be taken to directly lessen the day-to-day effects of sensory difficulties, which would in turn lessen their negative mental health implications.

“We have an aging society; everybody has a relative who’s getting older and having a harder time in life. It’s a burden for us all to share,” Pinto said. “Lessening the burdens of your aging relatives and friends can have a huge impact on people’s lives, their productivity and their quality of life.”

On a personal level, family members and friends can help by being patient and finding ways to communicate more effectively, such as speaking clearly or using written notes. On a societal level, public policies and community programs can ensure accessibility in public spaces and provide resources that improve quality of life.

Pinto also highlighted a wide range of technologies and medical interventions are available that can help compensate for sensory impairment. For hearing loss, there are cochlear implants, hearing aids and other hearing-assistive devices — which research has indicated could slow cognitive decline in addition to improving quality of life. For vision loss, there are glasses, contacts, cataract surgery and LASIK surgery, along with accommodations like text-to-speech computer programs. Even for the sense of smell, health experts can sometimes help by reducing sinus inflammation or conducting smell training exercises.

“In many cases, we can mitigate sensory difficulties in ways that might actually improve people’s lives, mental health and sense of loneliness — which is a huge epidemic,” Pinto said. “These are simple ways we can intervene to help people and potentially have a huge impact on society.”

Recognizing and destigmatizing sensory disability

The researchers said they intentionally used the word “disability” throughout the paper to underscore the significant impact of sensory impairments on individuals’ lives. This terminology also aligns with efforts to destigmatize these conditions and promote a more inclusive approach to healthcare.

“To some extent, our society already considers decreased sensory function to be a disability: think of the blind and d/Deaf communities,” Wang said. “Like many marginalized communities, the disabled community has historically had a very contentious relationship with the medical field, which can cause distress and limit access to mental health services. With better understanding and compassion, we can strive to improve the care we provide to older adults and disabled patients.”

He said that by framing the data this way, he hopes to encourage more healthcare providers to move away from thinking in terms of the Medical Model of Disability and move towards the Social Model of Disability.

“My understanding is that the Medical Model characterizes disability as something that is ‘deficient’ with a person, thus requiring some sort of ‘fixing’ of the individual,” he explained. “The Social Model characterizes disability as more of an identity, so limitations relating to disability stem from a society’s lack of accessibility and accommodation for disabled people.”

Recognizing sensory impairments as disabilities and acknowledging their impact on mental health are important steps toward more comprehensive and compassionate care. By addressing the medical, social and environmental barriers that exacerbate these impairments, clinicians — and society as a whole — can better support older adults in maintaining their independence.

It is a major risk factor for cirrhosis and liver cancer. And because treatment options are limited, MASH is the second leading cause for liver transplants in the United States after cirrhosis caused by chronic hepatitis C infection.

A better understanding of the pathological processes that drive MASH is critical to creating effective treatments. In a new paper published August 19, 2024 in PNAS, a team of scientists from Sanford Burnham Prebys, the University of California San Diego School of Medicine and elsewhere, describe the complex interplay between diseased liver cells and macrophages — a type of white blood cell whose jobs include killing and removing harmful cells and pathogens and helping to spur normal healing.

Debanjan Dhar, PhD, associate professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, is senior author of the study. David Brenner, MD, president and CEO of Sanford Burnham Prebys, and Christopher Glass, MD, PhD, professor of cellular and molecular medicine at UC San Diego, are corresponding authors. Souradipta Ganguly, PhD, a postdoctoral research fellow at UC San Diego and Sanford Burnham Prebys, is first author.

The researchers found that the heterogeneous mix of macrophages involved with MASH was different, depending on whether the disease was progressing or regressing. More importantly, they identified specific macrophage subpopulations that are critical for resolving MASH and liver fibrosis in which accumulating scar tissue impairs the organ’s ability to function or repair itself. These fibrotic bands restrict blood flow, imperiling the entire organ.

“In MASH, Kupffer cells (a type of macrophage that resides in the liver) are lost and replaced by four distinct macrophage subpopulations. When the disease is in regression — that is, symptoms or severity are decreasing — two lipid associated macrophage subpopulations are dominant and express TREM2, a cell receptor that regulates cell survival, proliferation and anti-inflammatory responses,” said Brenner.

“MASH regression occurs in the presence if TREM2+ macrophages. They not only restrict the progression of MASH-fibrosis, but effectively slow it and reduce inflammation. The absence of TREM2+ macrophages allows the disease to progress.”

In early and moderate stages, MASH often produces no tell-tale symptoms, which is part of the why it has reached epidemic proportions in the U.S. The American Liver Foundation estimates 80 to 100 million Americans have fatty liver disease which, undiagnosed and untreated, progresses to nonalcoholic steatohepatitis, MASH, cirrhosis, liver cancer and death, often in combination with other conditions, such as obesity.

An estimated 1.5% to 6.5% of U.S. adults have MASH. afflicted by the condition, and roughly 24% of adults have metabolic dysfunction-associated steatotic fatty liver disease, the starting point for MASH, cirrhosis and worse.

“Our findings suggest that lipid associated macrophages that express TREM2 and TREM2 are required both for the emergence of more liquid associated macrophages and for their reparative functions,” said Dhar.

“Effective degradation of scar tissue as a protective mechanism is mediated by TREM2, and the absence of TREM2+ macrophages not only disrupts the liver’s ability to remove fibrotic tissue, but it also harms the entire immune response and healing process.”

Going forward, the scientists say a TREM2 agonist — a drug or substance that mimics the function of TREM2 — might be beneficial for MASH/fibrosis therapy and help spur MASH and fibrosis regression in patients also undergoing lifestyle modification, weight loss or bariatric surgery.

“There is only one approved treatment for MASH, and it was only approved earlier this year,” said Glass. “Any opportunities to expand clinical options that benefit patients need to be thoroughly pursued because liver disease in this country — and around the world — is only getting worse.”

Additional authors on the study include Sara Brin Rosenthal, Kei Ishizuka, Theresa V. Rohm, Naser Khader, Sebastiano Archilei, Jerrold M. Olefsky, Ariel E. Feldstein, Tatiana Kisseleva and Rohit Loomba, all at UC San Diego; Ty D. Troutman, UC San Diego and Cincinnati Children’s Hospital Medical Center, and German Aleman Muench, Yasuyo Sano and Pejman Soroosh, Janssen Research & Development, San Diego.

This study was supported by National Institutes of Health grants to D.D. (R01DK137061, R01DK133930), Altman Clinical and Translational Research Institute (ACTRI — KL2TR001444) and the San Diego Digestive Diseases Research Center (NIH DK120515). It was partially supported by the ACTRI (NIH UL1TR001442). T.K. was supported by NIH grants DK099205, AA028550, DK101737, AA011999, DK120515, AA029019, DK091183; C.K.G by NIH grants DK091183 and HL147835. T.D.T. was supported by NIH grants P30DK063491, T32DK007044, P30DK078392, the American Association for the Study of Liver Diseases (PNC23-216751) and the Center for Inflammation and Tolerance through the Cincinnati Children’s Research Foundation. R.L. received funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835), the John C. Martin Foundation (RP124). J.M.O was supported by the Diabetes Research Center (P30DK063491) and Horton JPI MRA: Obesity and its metabolic complications (20175015). A.E.F was supported by the NIH grant R01DK113592. T.V.R was supported by grants from the Swiss National Science Foundation (P2BSP3_200177) and the Larry L. Hillblom Foundation (2023-D-012-FEL).