Great apes native to the rainforests of Indonesia and Malaysia, orangutans are marvels of adaptation to the vagaries of food supply in the wild, according to an international team of researchers led by a Rutgers University-New Brunswick scientist. The critically endangered primates outshine modern humans in avoiding obesity through their balanced choices of food and exercise, the scientists found.

The researchers reported their findings, based on 15 years of firsthand observations of wild orangutans in the jungles of Borneo, in Science Advances.

"These findings show how wild Bornean orangutans adapt to changes in their environment by adjusting their nutrient intake, behavior and energy use," said Erin Vogel, the Henry Rutgers Term Chair Professor in the Department of Anthropology in the School of Arts and Sciences, who led the study. "The work highlights the importance of understanding natural dietary patterns and their impact on health, both for orangutans and humans."

Orangutans are one of the closest living relatives to humans, sharing a common ancestor, Vogel said. This evolutionary relationship means that orangutans and humans have similar physiological and metabolic processes, dietary needs and behavioral adaptations. Studying orangutans can provide insights into the evolutionary adaptations that might also be relevant to humans, she said.

Humans also exhibit metabolic flexibility, Vogel said, but modern diets high in processed foods can disrupt this balance, leading to metabolic disorders such as diabetes.

While orangutans reduce physical activity during low fruit periods to conserve energy, Vogel said, humans, especially those with sedentary lifestyles, may not adjust their energy expenditure to match their caloric intake, leading to weight gain and associated health issues.

"Understanding these adaptations can help us learn more about how humans can manage their diets and health," Vogel said. "It also highlights the importance of conserving orangutan habitats to ensure their survival."

The research was conducted at the Tuanan Orangutan Research Station in the Mawas Conservation Area in Central Kalimantan, Indonesia, on the island of Borneo. The conservation area, a peat swamp forest, protects about 764,000 acres, an area roughly the size of Rhode Island. Peat forests are richly biodiverse, ancient ecosystems with landscapes dominated by waterlogged trees that grow on layers of dead leaves and plant material.

Understanding the dietary strategies of orangutans can inform better nutritional practices for humans, said Vogel, who also is director of the Center for Human Evolutionary Studies at Rutgers.

"In essence, the research on orangutans underscores the importance of dietary balance and metabolic flexibility, which are crucial for maintaining health in both orangutans and humans," Vogel said. "It suggests that modern dietary habits, characterized by high consumption of processed foods rich in sugars and fats, can lead to metabolic imbalances and health issues."

In earlier studies, Vogel and an international team of colleagues established the patterns by which orangutans fed. Orangutans prefer to eat fruit because it is rich in carbohydrates, but when fruit is scarce, they switch to eating more leaves, bark and other foods that can provide more protein but fewer sugary carbohydrates. In times of high fruit availability, orangutans still consume protein but get most of their energy from carbohydrates and fats in the fruit.

"We wanted to find out how their bodies handle these changes," Vogel said. "We tested how the availability of fruit affects their diet and how their bodies adapt to avoid energy imbalance. We looked at how they switch between different types of fuel - like fats and proteins - when preferred food availability changes."

To conduct the study, Vogel, research colleagues, students and a staff that mostly included field technicians indigenous to the island of Borneo collected data for more than a decade on what the orangutans ate daily and analyzed their urine to see how their bodies responded to any nutritional changes. This required staying in close proximity to the ape in the equatorial, humid jungle from dawn until night.

The scientists made a number of key findings:

• Orangutans avoid obesity as part of a response to the significant fluctuations - in both magnitude and duration - in fruit availability in their natural habitat. Unlike humans in Western culture, who have constant access to high-calorie foods, orangutans experience periods of both abundance and scarcity. The periods of scarcity and resulting low caloric intake, similar to humans' intermittent fasting, may help maintain their health by reducing oxidative stress.
• During periods of fruit scarcity, orangutans exhibit metabolic flexibility, switching to using stored body fat and muscle protein for energy. This allows them to survive when food is scarce.
• During periods of fruit scarcity, orangutans exhibit behavioral adaptability, relying on reduced physical activity as well as stored energy and muscles to conserve energy. They rest more, go to sleep earlier, travel less and spend less time with other orangutans. This flexibility enables them to use body fat and protein for fuel when needed. They rebuild fat reserves and muscle when fruit availability is high.
• The orangutan diet also prioritizes a consistent level of protein, which contrasts with a modern Western diet, which often can be rich in low-cost, energy-dense, protein-poor foods. Those choices contribute to obesity and metabolic diseases in humans.

This research builds on a report published earlier this year in The American Journal of Biological Anthropology, led by doctoral student Will Aguado, as the first author. This study found that orangutans at Tuanan get most of their protein from the leaves and seeds of just one out of nearly 200 species in the diet -- a vine called Bowringia callicarpa. The protein in this plant fuels orangutans through seasons of fruit scarcity and likely allows orangutans at Tuanan to persist and for their population to grow.

Other scientists on the study from Rutgers included Malcolm Watford, a professor in the Department of Nutritional Sciences, Rutgers School of Environmental and Biological Sciences; and former Rutgers doctoral student Rebecca Brittain, Tatang Mitra-Setia and Sri Suci Utami from Universitas Nasional in Indonesia, graduate students William Aguado, Astri Zulfa and Alysse Moldawer, all with the Department of Anthropology in the School of Arts and Sciences. Former graduate student Timothy Bransford, who also contributed to the study, is now at Eckerd College, St. Petersburg, Fla.

Researchers from the following institutions also contributed to the study: The Max Planck Institute of Animal Behavior and the University of Konstanz in Germany; Yale University; Jagiellonian University in Krakow, Poland; the University of Cincinnati; the University of Colorado; Eckerd College in St. Petersburg, Fla.; Universitas Nasional in Jakarta, Indonesia; National Research and Innovation Agency in Cibinong-Bogor, Indonesia; University of Zurich in Switzerland; Hunter College of the City University of New York; and the University of Sydney in Australia.

"This study shows that air pollution doesn't just increase the risk of dementia -- it actually makes Alzheimer's disease worse," said Edward Lee, MD, PhD, co-director of Penn's Institute on Aging. "As researchers continue to search for new treatments, it's important to uncover all of the factors that contribute to the disease, including the influence of the environment in which they live."

Health risks from tiny air particles

Air pollution is made up of fine particulate matter, or the tiny, inhalable particles, ranging from 10 micrometers to less than 2.5 micrometers wide, about half the width of a single strand of spider web. It can come from wildfire smoke, car exhaust, construction site debris, or combustion from factories. Particulate matter 2.5 micrometers and smaller (PM_2.5) is so small that when inhaled, the particles can be absorbed into the blood stream and cause health concerns. Previous research has linked air pollution containing PM_2.5 with dementia, loss of cognitive function, and accelerated cognitive decline.

The researchers examined brain samples from over 600 autopsies from the Penn Medicine Brain Bank. Using data from satellites and local air quality monitors, the researchers modeled the amount of PM_2.5 in the air based on where each person lived. They found that for every increase of 1 microgram per cubic meter of PM_2.5, the risk for worse Alzheimer's disease amyloid and tau buildup increased by 19 percent.

Further, when they examined the clinical records of these individuals, researchers found that those who lived in areas with high concentrations of PM_2.5 with advanced pathology also had greater cognitive impairment and more rapid onset of symptoms, including memory loss, difficulty with speech, and diminished judgement, compared to people who lived in areas with lower concentrations of air pollution.

While this study focused on exposures to PM_2.5 based on geographic location, researchers acknowledgethat they could not account for individual-specific exposures to air pollution, such as exposure to second-hand smoke in the home, or working with potentially dangerous chemicals.

"In the United States, air pollution is at the lowest levels in decades, but even just a year living in an area with high levels of pollution can have a big impact on a person's risk for developing Alzheimer's disease," said Lee. "It underscores the value of environmental justice efforts that focus on reducing air pollution to improve public health."

This research is funded by the National Institutes of Health and the National Institute of Environmental Health Sciences (P30AG072979, P01AG066597, U19AG062418, P01AG084497, and P30ES013508).

But why lack of sleep -- in particular the early, deep phase called non-REM sleep -- lowers levels of growth hormone has been a mystery.

In a study published in the current issue of the journal Cell, researchers from University of California, Berkeley, dissect the brain circuits that control growth hormone release during sleep and report a novel feedback mechanism in the brain that keeps growth hormone levels finely balanced.

The findings provide a map for understanding how sleep and hormone regulation interact. The new feedback mechanism could open avenues for treating people with sleep disorders tied to metabolic conditions like diabetes, as well as degenerative diseases like Parkinson's and Alzheimer's.

"People know that growth hormone release is tightly related to sleep, but only through drawing blood and checking growth hormone levels during sleep," said study first author Xinlu Ding, a postdoctoral fellow in UC Berkeley's Department of Neuroscience and the Helen Wills Neuroscience Institute. "We're actually directly recording neural activity in mice to see what's going on. We are providing a basic circuit to work on in the future to develop different treatments."

Because growth hormone regulates glucose and fat metabolism, insufficient sleep can also worsen risks for obesity, diabetes and cardiovascular disease.

The sleep-wake cycle

The neurons that orchestrate growth hormone release during the sleep-wake cycle -- growth hormone releasing hormone (GHRH) neurons and two types of somatostatin neurons -- are buried deep in the hypothalamus, an ancient brain hub conserved in all mammals. Once released, growth hormone increases the activity of neurons in the locus coeruleus, an area in the brainstem involved in arousal, attention, cognition and novelty seeking. Dysregulation of locus coeruleus neurons is implicated in numerous psychiatric and neurological disorders.

"Understanding the neural circuit for growth hormone release could eventually point toward new hormonal therapies to improve sleep quality or restore normal growth hormone balance," said Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author. "There are some experimental gene therapies where you target a specific cell type. This circuit could be a novel handle to try to dial back the excitability of the locus coeruleus, which hasn't been talked about before."

The researchers, working in the lab of Yang Dan, a professor of neuroscience and of molecular and cell biology, explored the neuroendocrine circuit by inserting electrodes in the brains of mice and measuring changes in activity after stimulating neurons in the hypothalamus with light. Mice sleep for short periods -- several minutes at a time -- throughout the day and night, providing many opportunities to study growth hormone changes during sleep-wake cycles.

Using state-of-the-art circuit tracing, the team found that the two small-peptide hormones that control the release of growth hormone in the brain -- GHRH, which promotes release, and somatostatin, which inhibits release -- operate differently during REM and non-REM sleep. Somatostatin and GHRH surge during REM sleep to boost growth hormone, but somatostatin decreases and GHRH increases only moderately during non-REM sleep to boost growth hormone.

Released growth hormone regulates locus coeruleus activity, as a feedback mechanism to help create a homeostatic yin-yang effect. During sleep, growth hormone slowly accumulates to stimulate the locus coeruleus and promote wakefulness, the new study found. But when the locus coeruleus becomes overexcited, it paradoxically promotes sleepiness, as Silverman showed in a study published earlier this year.

"This suggests that sleep and growth hormone form a tightly balanced system: Too little sleep reduces growth hormone release, and too much growth hormone can in turn push the brain toward wakefulness," Silverman said. "Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health."

Because growth hormone acts in part through the locus coeruleus, which governs overall brain arousal during wakefulness, a proper balance could have a broader impact on attention and thinking.

"Growth hormone not only helps you build your muscle and bones and reduce your fat tissue, but may also have cognitive benefits, promoting your overall arousal level when you wake up," Ding said.

The work was funded by the Howard Hughes Medical Institute (HHMI), which until this year supported Dan as an HHMI investigator, and the Pivotal Life Sciences Chancellor's Chair fund. Dan is the Pivotal Life Sciences Chancellor's Chair in Neuroscience. Other co-authors of the paper are Peng Zhong, Bing Li, Chenyan Ma, Lihui Lu, Grace Jiang, Zhe Zhang, Xiaolin Huang, Xun Tu and Zhiyu Melissa Tian of UC Berkeley; and Fuu-Jiun Hwang and Jun Ding of Stanford University.