Publisher Health

Researchers at the Obesity Research Unit of the University of Helsinki have found that obesity clearly reduces mitochondrial gene expression in fat tissue, or adipose tissue. Mitochondria are important cellular powerplants which process all of our energy intake. If the pathways associated with breaking down nutrients are lazy, the changes can often have health-related consequences.
A total of 49 pairs of identical twins discordant for body weight participated in the study conducted at the University of Helsinki: their body composition and metabolism were studied in detail, and biopsies from adipose and muscle tissue were collected. Multiple techniques for analysing the genome-wide gene expression, the proteome and the metabolome were used in the study.
The study was recently published in the journal Cell Reports Medicine.
According to the findings, the pathways responsible for mitochondrial metabolism in adipose tissue were greatly reduced by obesity. Since mitochondria are key to cellular energy production, their reduced function can maintain obesity. For the first time, the study also compared the effects of obesity specifically on the mitochondria in muscle tissue in these identical twin pairs: muscle mitochondria too were found to be out of tune, but the change was less distinct than in adipose tissue.
The study provided strong evidence of a connection between the low performance of adipose tissue mitochondria and a proinflammatory state. Furthermore, the findings indicate that metabolic changes in adipose tissue are associated with increased accumulation of fat in the liver, prediabetic disorders of glucose and insulin metabolism as well as cholesterol.
“If mitochondria, the cellular powerplants, are compared to the engine of a car, you could say that the power output decreases as weight increases. A low-powered mitochondrial engine may also generate toxic exhaust fumes, which can cause a proinflammatory state in adipose tissue and, consequently, the onset of diseases associated with obesity,” says Professor Kirsi Pietiläinen from the Obesity Research Unit, University of Helsinki.
“What was surprising was that the mitochondrial pathways in muscle had no association with these adverse health effects,” Pietiläinen adds.
Obesity also affected amino acid metabolism
In the study, changes in mitochondrial function were also seen in amino acid metabolism. The metabolism of branched-chain amino acids, which are essential to humans, was weakened in the mitochondria of both adipose tissue and muscle tissue.
“This finding was of particular significance because the reduced breakdown of these amino acids and the resulting heightened concentration in blood have also been directly linked with prediabetic changes and the accumulation of liver fat in prior twin studies,” says Pietiläinen.
Obesity, with its numerous associated diseases, is a common phenomenon that is continuously increasing in prevalence. While lifestyle influence the onset of obesity, genes also have a significant role.
“Identical twins have the same genes, and their weight is usually fairly similar. In fact, studying twins is the best way to investigate the interplay between genes and lifestyle. In spite of their identical genome, the genes and even mitochondria of twins can function on different activity levels. We utilised this characteristic in our study when looking into the effects of weight on tissue function,” Pietiläinen says.
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Early in the coronavirus pandemic, a team of immunologists from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg and physicians from the University of Freiburg Medical Center joined forces to learn more about immunity in people recovering from coronavirus infections. The study revealed a yet unknown involvement of Interleukin 33, an important alarm-signal, when immune cells get exposed to Sars-CoV-2 for a second time.
Since the beginning of the coronavirus pandemic, scientists and physicians worldwide undertook enormous efforts to understand the disease caused by the virus. In their latest collaborative study, researchers from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg and physicians from the University of Freiburg Medical Center unveil a novel feature of COVID-19 immunity, which could have implications for future therapies. The study points to the involvement of Interleukin 33, an important danger signal, when immune cells encounter Sars-CoV-2 for a second time.
“We started the study at a very early stage of the pandemic in 2020 when not much was known about the immune response post-infection,” says Erika Pearce, group leader at the Max Planck Institute of Immunobiology and Epigenetics. “Our aim was to examine the development of immunity in people recovering from Covid-19.”
Antibodies stick around
An infection with Sars-CoV-2 triggers a complex immune response necessary for the development of immunity to the virus. In simple terms, two linked branches of our immune system need to remember the virus to prevent reinfection, namely antibody-producing B cells and memory T cells. Understanding how this happens in Sars-CoV-2 infection is key for controlling the Covid-19 pandemic and critical for the success of the vaccination efforts.
For the study, the team examined blood samples of 155 individuals who mostly had mild disease. They measured the amount of antibodies against the SARS-CoV-2 spike protein and found that patients maintain high levels of antibodies more than two months after infection, indicating that they will likely be protected from re-infection. “We thought this was very encouraging, but we also wanted to understand better how the immune system would react to a second encounter with the virus,” says Petya Apostolova, physician and researcher in the lab of Erika Pearce.
When the virus hits the second time
Effective immunity to a virus is reached when sufficient antibodies and memory T cells are present in the blood of a person who has recovered from the disease or has been vaccinated. To test how this happens after Covid-19, the team exposed blood cells from participants who had antibodies against Sars-CoV-2 to a portion of the virus. They observed that memory T cells had developed and quickly responded to viral proteins. “We measured a broad panel of molecules that our immune cells use to communicate with each other. It was most fascinating to us that of all these measurements, the amount of Interleukin 33 was the closest match to the amount of antibodies people had, and to the activation of their memory T cells,” explains Apostolova. Interleukin 33 (IL-33) is released by cells that sense danger in their environment and has been previously linked to chronic lung disease. IL-33 can have beneficial effects by activating T cells and inducing antibody production, but it can also promote inflammation of the lung. For the first time, this study has linked IL-33 production to immunity to Sars-CoV-2.
“We believe that Interleukin 33, which is normally produced as an alarm-signal, could be an important link between protection and disease severity,” says Cornelius Waller from the University of Freiburg Medical Center. Indeed, by analyzing public data of lung cells taken from patients during Sars-CoV-2 infection, the researchers were able to show that Interleukin 33 was produced in their lungs. However, identifying the implications of these findings also in the context of lung tissue damage after severe Covid-19 infections will require more investigation.
The group of researchers hopes this collaboration will continue. As Waller pointed out, “we were able to discover this much so quickly through this fantastic synergy between clinicians experienced in the care for Covid-19 patients and experts in the immunology field.” The researchers hope that this study might pave the way to better understanding immunity to Sars-CoV-2 and other viral infections.

A team of scientists has analyzed how microbes in the gut process the plant-based, sulfur-containing sugar sulfoquinovose. Their study discovered that specialized bacteria cooperate in the utilization of the sulfosugar, producing hydrogen sulfide. This gas has disparate effects on human health: at low concentrations, it has an anti-inflammatory effect, while increased amounts of hydrogen sulfide in the intestine, in turn, are associated with diseases such as cancer.
Diet and the gut microbiome
With the consumption of a single type of vegetable such as spinach, hundreds of chemical components enter our digestive tract. There, they are further metabolized by the gut microbiome, a unique collection of hundreds of microbial species. The gut microbiome thus plays a major role in determining how nutrition affects our health. “So far, however, the metabolic capabilities of many of these microorganisms in the microbiome are still unknown. That means we don’t know what substances they feed on and how they process them,” explains Buck Hanson, lead author of the study and a microbiologist at the Center for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna. “By exploring the microbial metabolism of the sulfosugar sulfoquinovose in the gut for the first time, we have shed some light into this black box,” he adds. The study thus generates knowledge that is necessary to therapeutically target the interactions between nutrition and the microbiome in the future.
Sulfosugars from green plants and algae
Sulfoquinovose is a sulfonic acid derivative of glucose and is found as a chemical building block primarily in green vegetables such as spinach, lettuce, and in algae. From previous studies by the research group led by microbiologist David Schleheck at the University of Konstanz, it was known that other microorganisms can in principle use the sulfosugar as a nutrient. In their current study, the researchers from the Universities of Konstanz and Vienna used analyses of stool samples to determine how these processes specifically take place in the human intestine. “We have now been able to show that, unlike glucose, for example, which feeds a large number of microorganisms in the gut, sulfoquinovose stimulates the growth of very specific key organisms in the gut microbiome,” says David Schleheck. These key organisms include the bacterium of the species Eubacterium rectale, which is one of the ten most common gut microbes in healthy people. “The E. rectale bacteria ferment sulfoquinovose via a metabolic pathway that we have only recently deciphered, producing, among other things, a sulfur compound, dihydroxypropane sulfonate or DHPS for short, which in turn serves as an energy source for other intestinal bacteria such as Bilophila wadsworthia. Bilophila wadsworthia ultimately produces hydrogen sulfide from DHPS via a metabolic pathway that was also only recently discovered,” explains the microbiologist.
A question of dose: hydrogen sulfide in the intestine
Hydrogen sulfide is produced in the intestine by our own body cells as well as by specialized microorganisms and has a variety of effects on our body. “This gas is a Janus-faced metabolic product,” explains Alexander Loy, head of the research group at the University of Vienna. “According to current knowledge, it can have a positive but also a negative effect on intestinal health.” A decisive factor, he says, is the dose: in low amounts, hydrogen sulfide can have an anti-inflammatory effect on the intestinal mucosa, among other things. Increased hydrogen sulfide production by gut microbes, on the other hand, is associated with chronic inflammatory diseases and cancer. Until now, mainly sulfate and taurine, which are found in increased amounts in the intestine as a result of a diet rich in meat or fat, were known to be sources of hydrogen sulfide for microorganisms. The discovery that sulfoquinovose from green foods such as spinach and algae also contribute to the production of the gas in the gut therefore comes as a surprise.
“We have shown that we can use sulfoquinovose to promote the growth of very specific gut bacteria that are an important component of our gut microbiome. We now also know that these bacteria in turn produce the contradictory hydrogen sulfide from it,” Loy sums up. Further studies by the scientists from Konstanz and Vienna will now clarify whether and how the intake of the plant-based sulfosugar can have a health-promoting effect. “It is also possible that sulfoquinovose could be used as a so-called prebiotic,” adds Schleheck. Prebiotics are food ingredients or additives that are metabolized by specific microorganisms and used to explicitly support the intestinal microbiome.
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Stretching the time between the first and second doses would greatly accelerate the rate at which people get at least partial protection. But some experts fear it could also lead to new variants.The prospect of a fourth wave of the coronavirus, with new cases climbing sharply in the Upper Midwest, has reignited a debate among vaccine experts over how long to wait between the first and second doses. Extending that period would swiftly increase the number of people with the partial protection of a single shot, but some experts fear it could also give rise to dangerous new variants.In the United States, two-dose vaccines are spaced three to four weeks apart, matching what was tested in clinical trials. But in Britain, health authorities have delayed doses by up to 12 weeks in order to reach more people more quickly. And in Canada, which has precious few vaccines to go around, a government advisory committee recommended on Wednesday that second doses be delayed even longer, up to four months.Some health experts think the United States should follow suit. Dr. Ezekiel J. Emanuel, a co-director of the Healthcare Transformation Institute at the University of Pennsylvania, has proposed that for the next few weeks, all U.S. vaccines should go to people receiving their first dose.“That should be enough to quell the fourth surge, especially in places like Michigan, like Minnesota,” he said in an interview. Dr. Emanuel and his colleagues published the proposal in an op-ed on Thursday in USA Today.But opponents, including health advisers to the Biden administration, argue that delaying doses is a bad idea. They warn it will leave the country vulnerable to variants — those already circulating, as well as new ones that could evolve inside the bodies of partially vaccinated people who are not able to swiftly fight off an infection.“It’s a very dangerous proposal to leave the second dose to a later date,” said Dr. Luciana Borio, the former acting chief scientist of the Food and Drug Administration. Dr. Anthony S. Fauci, the nation’s top infectious-disease expert, agreed. “Let’s go with what we know is the optimal degree of protection,” he said.The seeds of the debate were planted in December, when clinical trials gave scientists their first good look at how well the vaccines worked. In the clinical trial for the Pfizer-BioNTech vaccines, for example, volunteers enjoyed robust protection from Covid-19 two weeks after the second dose. But just 10 days after the first dose, researchers could see that the volunteers were getting sick less often than those who got the placebo.In the same month, Britain experienced a surge of cases caused by a new, highly transmissible variant called B.1.1.7. Once the British government authorized two vaccines — from Pfizer-BioNTech and AstraZeneca — it decided to fight the variant by delaying the second doses of both formulations by 12 weeks.That policy has allowed Britain to get first doses into an impressive number of arms. As of Thursday, 48 percent of the British population has received at least one dose. By contrast, the United States has delivered at least one dose to just 33 percent of Americans.A mass Pfizer-BioNTech vaccination clinic set up at the Derby Arena in England last month.Oli Scarff/Agence France-Presse — Getty ImagesIn January, some researchers lobbied for the United States to follow Britain’s example.“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce a serious illness and deaths that are going to occur over the weeks ahead,” Michael T. Osterholm of the University of Minnesota said on Jan. 31 on NBC’s “Meet the Press.”But the government stayed the course, arguing that it would be unwise to veer off into the unknown in the middle of a pandemic. Although the clinical trials did show some early protection from the first dose, no one knew how well that partial protection would last.“When you’re talking about doing something that may have real harm, you need empirical data to back that,” said Dr. Céline R. Gounder, an infectious-disease specialist at Bellevue Hospital Center and a member of Mr. Biden’s coronavirus advisory board. “I don’t think you can logic your way out of this.”But in recent weeks, proponents of delaying doses have been able to point to mounting evidence suggesting that a first dose can provide potent protection that lasts for a number of weeks.The Centers for Disease Control and Prevention reported that two weeks after a single dose of either the Moderna or the Pfizer-BioNTech vaccine, a person’s risk of coronavirus infection dropped by 80 percent. And researchers in Britain have found that first-dose protection is persistent for at least 12 weeks.Dr. Emanuel argued that Britain’s campaign to get first doses into more people had played a role in the 95 percent drop in cases since their peak in January. “It’s been pretty stunning,” Dr. Emanuel said.He points to data like this as further evidence that the United States should stretch out vaccinations. He and his colleagues estimate that if the country had used a 12-week schedule from the start of its rollout, an additional 47 million people would have gotten at least one dose by April 5.Sarah E. Cobey, an epidemiologist and evolutionary biologist at the University of Chicago, said she thought that the United States had lost a precious opportunity to save many lives with such a strategy. “We’ve missed a window, and people have died,” she said.But even now, Dr. Emanuel said, it’s worth delaying doses. The United States is giving out roughly three million vaccines a day, but nearly half are going to people who have already received one shot. The nation’s entire supply, he argued, should instead be going instead to first-timers.If that happened, it would take two or three weeks for the United States to catch up with Britain, according to his team’s calculations. The extra protection would not just save the lives of the vaccinated but would help reduce transmission of the virus to people yet to get any protection.Still, some scientists say it’s premature to credit the delayed vaccination schedule for Britain’s drop in cases.“They’ve done a few other things, like shut down,” Dr. Fauci said.“I think the real test will be whether we see a rebound in cases now that the U.K. is reopening.” Dr. Gounder said.By some calculations, if all vaccines in the U.S. went to first-time recipients, it would take two or three weeks to catch up with Britain.Bryan Anselm for The New York TimesInstead of experimenting with vaccination schedules, critics say it would be wiser to get serious about basic preventive measures like wearing masks. “It’s crucial that we don’t just reopen into a big national party,” Dr. Borio said.She and others are also worried by recent studies that show that a single dose of Moderna or Pfizer-BioNTech does not work as well against certain variants, such as B.1.351, which was first found in South Africa.“Relying on one dose of Moderna or Pfizer to stop variants like B.1.351 is like using a BB gun to stop a charging rhino,” said John P. Moore, a virologist at Weill Cornell Medicine.Dr. Moore said he also worried that delaying doses could promote the spread of new variants that can better resist vaccines. As coronaviruses replicate inside the bodies of some vaccinated people, they may acquire mutations that allow them to evade the antibodies generated by the vaccine.But Dr. Cobey, who studies the evolution of viruses, said she wasn’t worried about delayed doses breeding more variants. “I would put my money on it having the opposite effect,” she said.Last week, she and her colleagues published a commentary in Nature Reviews Immunology in defense of delaying doses. Getting more people vaccinated — even with moderately less protection — could translate into a bigger brake on the spread of the virus in a community than if fewer people had stronger protection, they said. And that decline wouldn’t just mean more lives were saved. Variants would also have a lower chance of emerging and spreading.“There are fewer infected people in which variants can arise,” she said.Dr. Adam S. Lauring, a virologist at the University of Michigan who was not involved in the commentary, said he felt that Dr. Cobey and her colleagues had made a compelling case. “The arguments in that piece really resonate with me,” he said.Although it seems unlikely that the United States will shift course, its neighbor to the north has embraced a delayed strategy to cope with a booming pandemic and a short supply of vaccines.Dr. Catherine Hankins, a public health specialist at McGill University in Montreal and a member of Canada’s Covid-19 Immunity Task Force, endorsed that decision, based on the emerging evidence about single doses. And she said she thought that other countries facing even worse shortfalls should consider it as well.“I will be advocating at the global level that countries take a close look at Canada’s strategy and think seriously about it,” Dr. Haskins said.

An international research team led by Monash University has uncovered a new technique that could speed up recovery from bone replacements by altering the shape and nucleus of individual stem cells.
The research collaboration involving Monash University, the Melbourne Centre for Nanofabrication, CSIRO, the Max Planck Institute for Medical Research and the Swiss Federal Institute of Technology in Lausanne, developed micropillar arrays using UV nanoimprint lithography that essentially ‘trick’ the cells to become bone.
Nanoimprint lithography allows for the creation of microscale patterns with low cost, high throughput and high resolution.
When implanted into the body as part of a bone replacement procedure, such as a hip or knee, researchers found these pillars — which are 10 times smaller than the width of a human hair — changed the shape, nucleus and genetic material inside stem cells.
Not only was the research team able to define the topography of the pillar sizes and the effects it had on stem cells, but they discovered four times as much bone could be produced compared to current methods.
The findings were published in Advanced Science.

For the millions of people worldwide who have sickle cell disease, there are only a few treatment options, which include risky bone marrow transplants, gene therapy or other treatments that address a subset of symptoms. Today, researchers will describe the discovery of a small molecule with the potential to address the root cause of sickle cell disease by boosting levels of fetal hemoglobin, a healthy form that adults normally do not make. The drug could be formulated into a convenient daily tablet.
The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2021 is being held online April 5-30. 
“Using our proprietary small molecule probe and CRISPR guide RNA libraries, we screened a disease-relevant cell model that allowed us to pinpoint a treatment target,” says Ivan V. Efremov, Ph.D., senior director, head of medicinal chemistry of Fulcrum Therapeutics, who is presenting the work.
Sickle cell disease occurs when the gene responsible for instructing cells to produce two of hemoglobin’s four proteins contains an error. The mutation causes hemoglobin to adopt a rigid, sickle-like shape, which results in reduced oxygen transport throughout the body. The irregularly shaped cells get stuck in the blood vessels, causing painful episodes known as vaso-occlusive crises. The cells also die much sooner than normal red blood cells, leading to anemia. In addition to these symptoms, patients are at high risk of developing stroke, heart disease, kidney failure and other life-threatening conditions.
Interestingly, sickle cell patients don’t begin life with malfunctioning hemoglobin. While in the womb, humans make “fetal” hemoglobin that carries oxygen normally. Three or four months after birth, however, cells stop expressing fetal hemoglobin and switch to an adult version. The adult hemoglobin expressed by sickle cell patients is defective, but they still carry stem cells in their bone marrow with the potential to produce fetal hemoglobin.
Patients that have what is called a hereditary persistence of fetal hemoglobin tap this resource automatically. “They have the sickle cell mutation, but additional mutations result in continued expression of fetal hemoglobin into adulthood,” says Christopher Moxham, Ph.D., chief scientific officer of Fulcrum Therapeutics. With fetal hemoglobin levels around 25-30%, he says, enough red blood cell function is restored so that these patients may become asymptomatic.
The team developed a drug, called FTX-6058, that mimics the effect seen in patients with the hereditary persistence of fetal hemoglobin, as demonstrated in human-derived cell assay systems and mouse models. The drug attaches to a protein inside bone marrow stem cells destined to become mature red blood cells and reinstates their fetal hemoglobin expression. “What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” Efremov says. “If some red blood cells did not express this, they could still sickle and cause disease symptoms.” Fulcrum began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments showed an increase in fetal hemoglobin levels to around 25-30%.
“What distinguishes FTX-6058 is that we are targeting the root cause of sickle cell disease,” Moxham says. “Other drugs approved in this space, particularly since 2019, are treating the disease’s symptoms, either the anemia or the vaso-occlusive crises.” Preclinical experiments comparing FTX-6058 with another fetal hemoglobin booster, hydroxyurea, approved in the 1990s, showed the new drug candidate outperforms the current treatment and, according to Moxham, offers the potential for a transformative therapy.
The team is currently designing a phase 2 clinical trial for people living with sickle cell disease that they plan to initiate by the end of 2021. They are also in the process of characterizing the therapeutic molecule further, using genomic technologies and additional cell assay systems to fill in the details of exactly how it works. Beyond sickle cell disease, Fulcrum is also considering a clinical strategy to explore the use of FTX-6058 in people living with ?-thalassemia, a blood disorder in which hemoglobin production is reduced.
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A dementia diagnosis turns the world upside down, not only for the person affected but also for their relatives, as brain function gradually declines. Those affected lose their ability to plan, remember things or behave appropriately. At the same time, their motor skills also deteriorate. Ultimately, dementia patients are no longer able to handle daily life alone and need comprehensive care. In Switzerland alone, more than 150,000 people share this fate, and each year a further 30,000 new cases are diagnosed.
To date, all attempts to find a drug to cure this disease have failed. Dementia, including Alzheimer’s — the most common of several forms of dementia — remains incurable. However, a clinical study carried out in Belgium with the involvement of ETH researcher Eling de Bruin has now shown for the first time that cognitive motor training improves both the cognitive and physical skills of significantly impaired dementia patients. A fitness game, known as “Exergame,” developed by the ETH spin-off Dividat was used in the study.
Better cognitive ability thanks to training
In 2015, a team of scientists led by ETH researcher Patrick Eggenberger showed that older people who train both body and mind simultaneously demonstrate better cognitive performance and can thereby also prevent cognitive impairment (as reported by ETH News). However, this study was carried out on healthy subjects only.
“It has been suspected for some time that physical and cognitive training also have a positive effect on dementia,” explains de Bruin, who worked with Eggenberger at the Institute of Human Movement Sciences and Sport at ETH Zurich. “However, in the past it has been difficult to motivate dementia patients to undertake physical activity over extended periods.”
ETH spin-off combines exercise and fun
With a view to changing this, Eva van het Reve, a former ETH doctoral student, founded the ETH spin-off Dividat in 2013 together with her PhD supervisor Eling de Bruin and another doctoral student. “We wanted to devise a customised training programme that would improve the lives of older people,” says van het Reve. Fun exercises were developed in order to encourage people who were already experiencing physical and cognitive impairments to participate in training, and the Senso training platform was born.

Exercise and a healthy diet in childhood leads to adults with bigger brains and lower levels of anxiety, according to new UC Riverside research in mice.
Though diet and exercise are consistently recommended as ways to promote health, this study is the first to examine the long-lasting, combined effects of both factors when they are experienced early in life.
“Any time you go to the doctor with concerns about your weight, almost without fail, they recommend you exercise and eat less,” said study lead and UCR physiology doctoral student Marcell Cadney. “That’s why it’s surprising most studies only look at diet or exercise separately. In this study, we wanted to include both.”
The researchers determined that early-life exercise generally reduced anxious behaviors in adults. It also led to an increase in adult muscle and brain mass. When fed “Western” style diets high in fat and sugar, the mice not only became fatter, but also grew into adults that preferred unhealthy foods.
These findings have recently been published in the journal Physiology and Behavior. To obtain them, the researchers divided the young mice into four groups — those with access to exercise, those without access, those fed a standard, healthy diet and those who ate a Western diet.
Mice started on their diets immediately after weaning, and continued on them for three weeks, until they reached sexual maturity. After an additional eight weeks of “washout,” during which all mice were housed without wheels and on the healthy diet, the researchers did behavioral analysis, measured aerobic capacity, and levels of several different hormones.

As demonstrated by multiple studies over the years, women who breastfeed have a lower risk for developing cardiovascular disease and diabetes when compared to those who don’t or can’t. However, the mechanisms by which these risks are reduced for lactating women are still not fully understood.
Duke Appiah, Ph.D., an assistant professor of public health at the Texas Tech University Health Sciences Center and director of the university’s master’s program in public health, said the presence of excess fat, specifically visceral and pericardial fat could help explain this finding. Using that hypothesis, Appiah and a team of researchers recently completed a study titled, “The Association of Lactation Duration with Visceral and Pericardial Fat Volumes in Parous Women: The CARDIA Study.” The Journal of Clinical Endocrinology & Metabolism published the results in its February issue.
The Appiah team included Cora E. Lewis, M.D., and James M. Shikany (University of Alabama at Birmingham); David R. Jacobs, Jr., Ph.D., and Myron Gross, Ph.D., (University of Minnesota); Jeff Carr, M.D., (Vanderbilt University Medical Center); and Charles P. Quesenberry, Jr., Ph.D., Stephen Sidney, M.D., and senior research scientist Erica P. Gunderson, Ph.D., (Kaiser Permanente Northern California). The National Institute of Diabetes and Digestive and Kidney Diseases provided funding to Gunderson, the study’s senior author, for creating the pregnancy-related derived variables, and for the analysis of lactation and the development of cardiometabolic diseases in Coronary Artery Risk Development in Young Adults (CARDIA) study women.
Visceral fat, often referred to as active fat, potentially can increase the risk of developing dangerous health issues such as cardiovascular disease, heart attacks, Type 2 diabetes, stroke, breast and colorectal cancer and Alzheimer’s disease. Though it can build up in the arteries, visceral fat typically is stored within the abdominal cavity near critical organs such as the stomach, liver and intestines.
Pericardial fat, a deposit of fatty tissue located on the outside of the heart, also may influence certain cardiovascular conditions.
“We know these two organ-related fats contribute to diabetes as well as cardiovascular disease, so we wanted to see how breastfeeding influences these types of fat,” Appiah explained. “If breastfeeding does affect these fats, then it means it could provide a physiologic mechanism by which we can understand how breastfeeding actually affects these two main diseases. That was basically the motivation for this study.”
Because these fats are related to insulin production and other cardio metabolic factors, Appiah said weight change could influence the relationship between breastfeeding and these fats. For instance, the visceral fat that builds up around the abdomen tends to also include adipokines, which are cytokines produced by fatty tissue. Adipokines also secrete hormones, which influence the insulin sensitivity of the muscles. When the amount of visceral fat increases, so too does the competition for insulin binding sites, which increases the risk of developing insulin resistance or glucose intolerance.

The good news: There are more shots available. The challenge is getting people to take them.When it comes to getting the coronavirus vaccine, Mississippi residents have an abundance of options. On Thursday, there were more than 73,000 slots to be had on the state’s scheduling website, up from 68,000 on Tuesday.In some ways, the growing glut of appointments in Mississippi is something to celebrate: It reflects the mounting supplies that have prompted states across the country to open up eligibility to anyone over 16.But public health experts say the pileup of unclaimed appointments in Mississippi exposes something more worrisome: the large number of people who are reluctant to get inoculated.“It’s time to do the heavy lifting needed to overcome the hesitancy we’re encountering,” said Dr. Obie McNair, an internal medicine practitioner in Jackson, the state capital, whose office has a plentiful supply of vaccines but not enough takers.Though access remains a problem in rural Mississippi, experts say that the state — one of the first to open eligibility to all adults three weeks ago — may be a harbinger of what much of the country will confront in the coming weeks, as increasing supplies enable most Americans who want the vaccine to easily make appointments.The hesitancy has national implications. Experts say between 70 percent to 90 percent of all Americans must be vaccinated for the country to reach herd immunity, the point at which the virus can no longer spread through the population.When it comes to rates of vaccination, Mississippi still has a way to go, with just a quarter of all residents having received at least one dose compared to the nationwide average of 33 percent, according to state data. Other southern states, among them Tennessee, Arkansas, Alabama and Georgia, have similarly low rates of vaccination.A closer look at Mississippi’s demographics explains why hesitancy may be especially pronounced.The state reliably votes Republican, a group that remains highly skeptical of the coronavirus vaccine. Nearly half of all Republican men and 40 percent of Republicans over all have said they do not plan to get vaccinated, according to several recent surveys. Those figures have barely budged in the months since vaccines first became available. By contrast, just 4 percent of Democrats have said they will not get the vaccine.Another factor in the state’s low vaccination rate may be Mississippi’s large Black community, which comprises 38 percent of the state’s population but accounts for 31 percent of the doses administered, according to state data. Vaccine hesitancy remains somewhat high among African-Americans, though the doubts and distrust — tied largely to past government malfeasance like the notorious Tuskegee syphilis experiments — have markedly declined in recent months.According to a survey by the Kaiser Family Foundation released last week, about 55 percent of Black adults said they had been vaccinated or planned to be soon, up 14 percentage points from February, a rate that approaches those of Hispanics, at 61 percent, and whites, at 64 percent.Gov. Tate Reeves of Mississippi during a Covid briefing in February. “I feel much better waking up every day knowing that I have been vaccinated,” Governor Reeves said on Tuesday.Rogelio V. Solis/Associated PressA number of other heavily Republican states are also finding themselves with surfeits of doses. On Thursday, officials in Oklahoma, which has delivered at least one dose to 34 percent of its residents, announced they would open up eligibility to out-of-state residents, and in recent weeks, Republican governors in Ohio and Georgia voiced concern about the lackluster vaccine demand among their residents.Tim Callaghan, an assistant professor at the Texas A&M University School of Public Health and an expert on vaccine skepticism, said that more research was needed to divine the reasons behind Mississippi’s slackening vaccine demand but that states with large rural populations, Republican voters and African-Americans were likely to be the first to confront the problem. “If you’re looking to see vaccine hesitancy to emerge, it’s going to be in red states like Mississippi,” he said.Mississippi officials are well aware of the challenge. On Tuesday, Gov. Tate Reeves held a news conference with a panel of medical experts who sought to dispel some of the misinformation surrounding the vaccines. They tried to explain the vaccine development process, rebutted claims that the vaccine can cause miscarriages and recounted their own personal experiences after getting the shot.“I had about 18 hours of turbulence,” Governor Reeves said, describing the mild, flulike symptoms he had felt after his second injection. “But I was able to continue and move on and work, and I feel much better waking up every day knowing that I have been vaccinated.”Access is still a challenge in swaths of rural Mississippi, especially among African-Americans who live far from the drive-through vaccination sites in urban areas that account for roughly half the doses administered by the state. The scheduling system has also proved frustrating for the poor and for older people, who often lack internet access to book appointments or the transportation to get them to distant vaccination sites.“We’ve got to take the vaccines to the people, to pop-up locations that don’t require internet or registration in advance,” said Pam Chatman, the founder of Boss Lady Workforce Transportation, a system of minivans that has been ferrying residents in the Mississippi Delta to mass vaccination locations.Demand among African-Americans was still robust, she said, noting long lines that formed this week outside a tent in Indianola, a small city in the Delta, where the single-dose Johnson & Johnson vaccine was being offered. (The tents offering the Pfizer and Moderna vaccines, which require two doses, were nearly empty.)But hesitancy is rife. Dr. Vernon Rayford, an internal medicine doctor in Tupelo, said he had been frustrated by patients who offered up a variety of reasons for rejecting the vaccine. They claim it will give them Covid-19 or render them infertile, and they worry about unknown repercussions that might emerge decades down the road. “I’ve heard some really wacky theories,” he said.A drive-through vaccination site on the campus of Delta State University in Cleveland, Miss., last month.Rory Doyle for The New York TimesDr. Rayford, who sees patients of all races, said he had discerned subtle differences in the skepticism: African-Americans voice mistrust of the health care system, while whites express a more amorphous distrust of government. “It’s like that line from ‘Anna Karenina,’” he said. “‘All happy families are alike; each unhappy family is unhappy in its own way.’”Dr. Brian Castrucci, president of the de Beaumont Foundation, which focuses on public health, has been working on ways to allay such fears. Dr. Castrucci, an epidemiologist, is especially worried about young conservatives, ages 18 to 34; he cited a recent survey that found that 55 percent of college-educated Republican women under age 49 would not get vaccinated.“Its polls like these that keep me awake at night,” he said.The biggest obstacles to greater vaccine acceptance, he said, are the misinformation that flourishes on social media and the mixed messaging from Republican governors that leave people confused.“By relaxing Covid restrictions, elected leaders in states like Florida, Mississippi, Texas and Georgia are pushing narratives about coronavirus that are working against a narrative that promotes the urgency of vaccinations,” he said. “And unfortunately, our vaccine campaigns are being undone late at night by Facebook and Twitter and Instagram.”Until now, Mississippi health officials have been focusing much of their vaccine hesitancy efforts on African-American and Hispanic residents through partnerships with churches and health clinics. Governor Reeves, a Republican, has so far declined to single out skepticism among white conservatives in the state, but health officials said they were planning to address the problem through Facebook and Zoom meetings with local organizations.Public health experts say what’s needed are well-crafted messages delivered by doctors, religious leaders and other figures who are trusted in a particular community. Dr. Thomas Friedan, a former director of the Centers for Disease Control and Prevention who took part in a focus group with vaccine-hesitant Trump voters that was organized last month by the de Beaumont Foundation, said participants wanted their fears acknowledged, and they craved factual information without being lectured or belittled. “There isn’t one right way to communicate about vaccines, but you need multiple messages with multiple messengers,” said Dr. Friedan, who leads the health advocacy group Resolve to Save Lives. “And people don’t want to hear from politicians.”