Publisher Health

Mitochondria are important cellular power plants whose diminished activity has been previously demonstrated to be associated with obesity by a group of researchers at the University of Helsinki. Now, in a new international study coordinated by the University of Helsinki, the researchers have determined that the method of weight loss affects the metabolic pathways of mitochondria in fat tissue, also known as adipose tissue.
The study was recently published in the Journal of Clinical Endocrinology and Metabolism.
The researchers combined two datasets on calorie restriction diets and two datasets on weight loss surgery, or bariatric surgery, from Europe, monitoring dieters’ weight loss as well as metabolism. A biopsy was taken from the study subjects’ adipose tissue both at the beginning and the end of their weight reduction.
Ordinary dieting based on calorie restrictions put the mitochondria in the adipose tissue out of tune, further reducing the expression of related genes. In the case of similar weight loss resulting from bariatric surgery, the function of mitochondrial genes was improved and the activity level of mitochondrial metabolic pathways was higher.
The analyses conducted in the study were set in proportion to weight loss so that the results did not depend on greater weight loss in patients who had undergone surgery.
Why does lost weight come back? Impaired mitochondrial function is a potential cause.
Weight loss brings improvements to many metabolic changes associated with obesity, including disorders of glucose and lipid metabolism. Such beneficial effects were also observed in the new study, both in those who followed a regular diet and in those who underwent bariatric surgery.
“This is why it was astonishing to see that the activity of mitochondrial metabolic pathways in adipose tissue was entirely opposite in the two different groups,” says researcher Birgitta van der Kolk from the University of Helsinki’s Obesity Research Unit.
“Our observations indicate that impaired mitochondrial activity after losing weight by dieting may be the cause of adipose tissue rapidly building up again after weight loss. At the same time, bariatric surgery patients are better protected against regaining weight, which makes us suspect that a recovery of activity by mitochondria in the adipose tissue may be a factor underlying this phenomenon,” says Professor Kirsi Pietiläinen, who led the study.
The study utilised a technique known as transcriptomics analysis, which makes it possible to read the genome as a whole.
“By combining these broad-based techniques, biocomputing and extensive European datasets, we observed entirely unexpected links between dieting and the mitochondria of adipose tissue. In the future, it is important to investigate the relevance of these mechanisms to the functioning of such tissue and weight regain,” Pietiläinen adds.
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Materials provided by University of Helsinki. Note: Content may be edited for style and length.

If you reach for water when a muscle cramp strikes, you might want to think again. New research from Edith Cowan University (ECU) has revealed drinking electrolytes instead of pure water can help prevent muscle cramps.
The study, published in the Journal of the International Society of Sports Nutrition, found that people who drank electrolyte enhanced water during and after exercise were less susceptible to muscle cramps than those who drank pure water.
Muscle cramps are a common painful condition affecting many people, including around 39 per cent of marathon runners, 52 per cent of rugby players and 60 per cent of cyclists.
Dilution solution
Lead researcher Professor Ken Nosaka, from ECU’s School of Medical and Health Sciences, said the study builds on the evidence that a lack of electrolytes contributes to muscle cramps, not dehydration.
“Many people think dehydration causes muscle cramps and will drink pure water while exercising to prevent cramping,” he said.

Scientists are learning that a lesser-studied region on the pandemic coronavirus is recognized by COVID-19 infection-fighting antibodies. These antibodies were identified in blood samples from previously infected patients, and were found to potently prevent the virus from infecting cells.
The coronavirus spike protein is the key that unlocks the door to the cell, and antibodies bind to the spike protein to jam this function. Much attention has been given to studying antibodies that target the receptor-binding domain on the coronavirus spike protein. (The receptor-binding domain of the spike is responsible for triggering the merging of the virus with a host cell to achieve a takeover.)
However, some of the recovered patients’ antibodies blocked the coronavirus by binding to a different place on the virus spike — the N-terminal domain. These antibodies were as strong as those that bind to receptor-binding domain, a recent study shows.
Using electron cryo-microscopy (cryoEM) to map where these antibodies bound showed that all the antibodies that prevent infection bind a single place on the N-terminal domain. The research published in Cell demonstrated that these antibodies protected Syrian hamsters from SARS-CoV-2, the coronavirus that causes COVID-19 in people.
Additional recent findings indicate that the virus is slowly defying these antibodies that people are acquiring. The virus is adapting to these antibodies by accumulating mutations that help the virus escape these defenses, becoming so-called variants-of-concern.
Some of these variants, such as those first detected in the United Kingdom and South Africa, contain mutations that appear to make the virus less vulnerable to the neutralizing power of the N-terminal domain antibodies.

People who start eating before 8:30 a.m. had lower blood sugar levels and less insulin resistance, which could reduce the risk of developing type 2 diabetes, according to a study presented virtually at ENDO 2021, the Endocrine Society’s annual meeting.
“We found people who started eating earlier in the day had lower blood sugar levels and less insulin resistance, regardless of whether they restricted their food intake to less than 10 hours a day or their food intake was spread over more than 13 hours daily,” said lead researcher Marriam Ali, M.D., of Northwestern University in Chicago, Ill.
Insulin resistance occurs when the body doesn’t respond as well to the insulin that the pancreas is producing and glucose is less able to enter the cells. People with insulin resistance may be at higher risk of developing type 2 diabetes. Both insulin resistance and high blood sugar levels affect a person’s metabolism, the breaking down of food to its simpler components: proteins, carbohydrates (or sugars), and fats. Metabolic disorders such as diabetes occur when these normal processes become disrupted.
“With a rise in metabolic disorders such as diabetes, we wanted to expand our understanding of nutritional strategies to aid in addressing this growing concern,” Ali said. Previous studies have found that time-restricted eating, which consolidates eating to a shortened timeframe each day, has consistently demonstrated improvement in metabolic health, she noted. Her group wanted to see whether eating earlier in the day affected metabolic measures.
The researchers analyzed data from 10,575 adults who participated in the National Health and Nutrition Examination Survey. They divided participants into three groups depending on total duration of food intake: less than 10 hours, 10-13 hours, and more than 13 hours per day. They then created six subgroups based on eating duration start time (before or after 8:30 a.m.).
They analyzed this data to determine if eating duration and timing were associated with fasting blood sugar levels and estimated insulin resistance. Fasting blood sugar levels did not differ significantly among eating interval groups. Insulin resistance was higher with shorter eating interval duration, but lower across all groups with an eating start time before 8:30 a.m.
“These findings suggest that timing is more strongly associated with metabolic measures than duration, and support early eating strategies,” Ali said.
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Materials provided by The Endocrine Society. Note: Content may be edited for style and length.

A study conducted at Columbia University Mailman School of Public Health reports a high global prevalence of both depression and anxiety during the COVID-19 pandemic and shows how implementation of mitigation strategies including public transportation and school closures, and stay-at-home orders impacted such disorders. The results are published in Psychological Medicine.
“Our research found an elevated global prevalence of these mental health issues during COVID-19 and also revealed there was a wide variance in each at the region- and country-level,” said, João Castaldelli-Maia, MD, PhD, NIDA-INVEST Postdoctoral Fellow in the Department of Epidemiology, and lead author. In particular, Asia (most studies came from China) presented lower levels of both anxiety and depression, compared to the other regions of the world. Closure of public transportation increased levels of anxiety, whether it was two weeks or four weeks past the passage of closure enactment, especially in Europe.”
Using an end date of July 29th, 2020, the researchers analyzed data from Pubmed, MEDLINE, Web of Science, and medRxiv, among other databases, for depression and anxiety prevalence. They also reviewed the Oxford Covid-19 Government Response Tracker for the containment and closure policies indexes; and the Global Burden of Disease Study for previous levels of depression and anxiety. The WHO database which includes COVID literature for studies published by the same date was also used.
In total, 226,638 individuals were assessed within 60 included studies. Global prevalence of both depression and anxiety during the COVID-19 pandemic were 24 percent and 21 percent, respectively. Asia with rates of 18 percent for each, and China especially, had the lowest prevalence of both disorders. Regarding the impact of mitigation strategies on mental health — whether it was public transportation closures, school closings, workplace closures, cancellation of public events, or restrictions on gathering — only public transportation closures increased prevalence of anxiety, especially in Europe.
Castaldelli-Maia and colleagues found a 21 percent global prevalence of anxiety. Asia had lower levels of anxiety (18 percent) compared to other regions of the world (29 percent). In this case, Europe did not differ from Asia and other regions of the world. Again, a subgroup analysis at the country-level showed that China had a lower prevalence of anxiety at 15.5 percent compared to all other countries at 26 percent.
“Our study confirms how critical it is to investigate levels of mental health disorders and the possible impacts of social distancing measures on mental health outcomes, according to Silvia Martins, MD, PhD, associate professor of Epidemiology at Columbia Mailman School, and senior author. “Mental health concerns should not be viewed only as a delayed consequence of the COVID-19 pandemic, but also as a concurrent epidemic.”
Within the subgroup of Asian countries, estimates of depression prevalence ranged from 15 percent to 20 percent. When comparing the prevalence of depression in the pre-and post-COVID-19 eras, the estimates ranging from 1.3-3.4 percent, are demonstrably larger after the initiation of COVID-19.

Our knowledge of Alzheimer’s disease has grown rapidly in the past few decades but it has proven difficult to translate fundamental discoveries about the disease into new treatments. Now researchers at the California National Primate Research Center at the University of California, Davis, have developed a model of the early stages of Alzheimer’s disease in rhesus macaques. The macaque model, published March 18 in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association could allow better testing of new treatments.
The model was developed by Professor John Morrison’s laboratory at the CNPRC, in collaboration with Professor Jeffrey Kordower of Rush University Medical Center and Paramita Chakrabarty, assistant professor at the University of Florida.
Alzheimer’s disease is thought to be caused by misfolding of the tau and amyloid proteins. Misfolded proteins spread through the brain, leading to inflammation and cell death. Tau protein is commonly found in neurons of the brain and central nervous system, but not elsewhere.
Researchers think that decades may elapse between the silent beginnings of the disease and the first signs of cognitive decline. Understanding what happens over these years could be key to preventing or reversing symptoms of Alzheimer’s disease. But it is difficult to study therapeutic strategies without a powerful animal model that resembles the human condition as closely as possible, Morrison said. Much research has focused on transgenic mice that express a human version of amyloid or tau proteins, but these studies have proven difficult to translate into new treatments.
New translational models needed
Humans and monkeys have two forms of the tau protein in their brains, but rodents only have one, said Danielle Beckman, postdoctoral researcher at the CNPRC and first author on the paper.

Low doses of propylparaben — a chemical preservative found in food, drugs and cosmetics — can alter pregnancy-related changes in the breast in ways that may lessen the protection against breast cancer that pregnancy hormones normally convey, according to University of Massachusetts Amherst research.
The findings, published March 16 in the journal Endocrinology, suggest that propylparaben is an endocrine-disrupting chemical that interferes with the actions of hormones, says environmental health scientist Laura Vandenberg, the study’s senior author. Endocrine disruptors can affect organs sensitive to hormones, including the mammary gland in the breast that produces milk.
“We found that propylparaben disrupts the mammary gland of mice at exposure levels that have previously been considered safe based on results from industry-sponsored studies. We also saw effects of propylparaben after doses many times lower, which are more reflective of human intake,” Vandenberg says. “Although our study did not evaluate breast cancer risk, these changes in the mammary tissue are involved in mitigating cancer risk in women.”
Hormones produced during pregnancy not only allow breast tissue to produce milk for the infant, but also are partly responsible for a reduced risk of breast cancer in women who give birth at a younger age.
The researchers, including co-lead author Joshua Mogus, a Ph.D. student in Vandenberg’s lab, tested whether propylparaben exposure during the vulnerable period of pregnancy and breastfeeding adversely alters the reorganization of the mammary gland. They examined the mothers’ mammary glands five weeks after they exposed the female mice to environmentally doses of propylparaben during pregnancy and breastfeeding.
Compared with pregnant mice that had not received propylparaben, the exposed mice had mammary gland changes not typical of pregnancy, the researchers report. These mice had increased rates of cell proliferation, which Vandenberg says is a possible risk factor for breast cancer. They also had less-dense epithelial structures, fewer immune cell types and thinner periductal collagen, the connective tissue in the mammary gland.
“Some of these changes may be consistent with a loss of the protective effects that are typically associated with pregnancy,” says Mogus, who was chosen to present the research, deemed “particularly newsworthy” by the Endocrine Society, at the international group’s virtual annual meeting, ENDO 2021, beginning March 20.
Mogus says future studies should address whether pregnant females exposed to propylparaben are actually more susceptible to breast cancer. “Because pregnant women are exposed to propylparaben in many personal care products and foods, it is possible that they are at risk,” Mogus says, adding that pregnant and breastfeeding women should try to avoid using products containing propylparaben and other parabens.
“This chemical is so widely used, it may be impossible to avoid entirely,” Mogus adds. “It is critical that relevant public health agencies address endocrine-disrupting chemicals as a matter of policy.”
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Materials provided by University of Massachusetts Amherst. Note: Content may be edited for style and length.

Scientists at Sanford Burnham Prebys Medical Discovery Institute demonstrated for the first time that blocking “cell drinking,” or macropinocytosis, in the thick tissue surrounding a pancreatic tumor slowed tumor growth — providing more evidence that macropinocytosis is a driver of pancreatic cancer growth and is an important therapeutic target. The study was published in Cancer Discovery, a journal of the American Association for Cancer Research.
“Now that we know that macropinocytosis is ‘revved up’ in both pancreatic cancer cells and the surrounding fibrotic tissue, blocking the process might provide a ‘double whammy’ to pancreatic tumors,” says Cosimo Commisso, Ph.D., associate professor and co-director of the Cell and Molecular Biology of Cancer Program at Sanford Burnham Prebys and senior author of the study. “Our lab is investigating several drug candidates that inhibit macropinocytosis, and this study provides the rationale that they should be advanced as quickly as possible.”
Pancreatic cancer remains one of the deadliest cancers. Only one in ten people survive longer than five years, according to the American Cancer Society, and its incidence is on the rise. Pancreatic cancer is predicted to become the second-leading cause of cancer-related deaths in the U.S. by 2030.
“If we want to create a world in which all people diagnosed with pancreatic cancer will thrive, we first need to understand the key drivers of tumor growth,” says Lynn Matrisian, Ph.D., chief science officer at the Pancreatic Cancer Action Network (PanCAN), who wasn’t involved in the study. “This study suggests that macropinocytosis is an important target for drug development, and that progressing this novel treatment approach may help more people survive pancreatic cancer.”
Starving the stroma
Pancreatic tumors are surrounded by an unusually thick layer of stroma, or glue-like connective tissue that holds cells together. This stromal barrier makes it difficult for treatments to reach the tumor, and fuels tumor growth by providing the tumor with nutrients. Commisso’s previous research showed that rapidly growing pancreatic tumors obtain nutrients through macropinocytosis, an alternative route that normal cells don’t use — and he wondered if macropinocytosis in the stroma may also fuel tumor growth.
To test this hypothesis, Commisso and his team blocked macropinocytosis in cells that surround and nourish pancreatic tumors, called pancreatic cancer-associated fibroblasts (CAFs), and co-transplanted the modified cells with pancreatic tumor cells into mice. The scientists found that tumor growth slowed in these mice — compared to control groups in which macropinocytosis remained active in the stroma — suggesting that the approach holds promise as a way to treat pancreatic cancer.
“We are excited about this approach because instead of removing the stroma, which can cause the tumor to spread throughout the body, we simply block the process that is driving tumor growth,” says Yijuan Zhang, Ph.D., postdoctoral researcher in the Commisso lab and first author of the study. “We also deciphered the molecular signals that drive macropinocytosis in the stroma, providing new therapeutic avenues for pancreatic cancer researchers to explore.”
Promising drug targets identified
Based on their ongoing macropinocytosis research, the scientists have identified many druggable targets that may inhibit the process. Bolstered by this study’s findings, they will continue to investigate the promise of drug candidates that inhibit macropinocytosis as potential pancreatic cancer treatments.
“We already knew that macropinocytosis was a very important growth driver for pancreatic cancer, as well as lung, prostate, bladder and colon tumors,” says Commisso. “This study further spurs our efforts to advance a drug that targets macropinocytosis, which may be the breakthrough we need to finally put an end to many deadly and devastating cancers.”

The triggers and causes of a severe scarring disease of the lungs — idiopathic pulmonary fibrosis, or IPF — remain unclear.
Now research published in Science Translational Medicine shows how cadmium and carbon black can trigger lung macrophages to produce a modified protein, citrullinated vimentin, or cit vim, which leads to lung fibrosis. Researchers from the University of Alabama at Birmingham and three other American universities also describe a sequence of mechanistic steps in lung macrophages and lung fibroblasts that leads to the lung scarring.
One of the enzymes involved in these steps — peptidylarginine deiminase 2, or PAD2 — may be a promising target to attenuate cadmium/carbon black-induced fibrosis, they say. The researchers also report a potential disease model for lung fibrosis and IPF — the use of cadmium chloride to induce interstitial fibrosis in mice.
The study, led by Veena Antony, M.D., included patients with IPF, tissue experiments and mouse models. Antony is the Endowed Professor of Environmental Medicine in the UAB Department of Medicine, and she directs the UAB Superfund Research Program.
“Altogether, these studies support a role for cit-vim as a damage-associated molecular pattern molecule, or DAMP, that is generated by lung macrophages in response to environmental cadmium/carbon black exposure,” Antony said. Cadmium is a toxic heavy metal recognized as a cause of lung fibrosis. Cadmium can adsorb onto carbon black particles. In the lung, such particles are ingested by macrophages, the sentinel host defense cells of the mammalian lung. Up to two-thirds of IPF patients have a history of smoking, and cigarette smoke contains both cadmium and carbon black. Air pollution from biomass fuels and coal furnaces is also a source of the two pollutants.
Data from human subjects
The researchers evaluated cadmium and cit-vim accumulation in tissue, using lung biopsies from 25 subjects with IPF — eight never-smokers and 17 smokers — and 14 controls — eight never-smokers and six smokers.