Cutting down daily sedentary time can have a positive effect on the risk factors of cardiovascular disease and type 2 diabetes in as little as three months, according to a study published in the Journal of Science and Medicine in Sport. The study findings suggest that simply one hour less sitting daily and increasing light physical activity can help in the prevention of these diseases.
Regular exercise is well known to be beneficial in weight management and prevention of chronic diseases. However, many adults do not meet the weekly recommendation of 2.5 hours of moderate-intensity exercise, and the majority of the day is typically spent sitting.
In an intervention study, researchers investigated whether health benefits can be achieved by reducing daily sedentary time during a three-month intervention period. The research participants were sedentary and physically inactive working-age adults with an increased risk of type 2 diabetes and cardiovascular diseases.
The researchers compared two groups: the intervention group was guided to reduce their sitting time by one hour per day by increasing standing and light-intensity physical activity, while the control group was instructed to maintain their usual habits and sedentary lifestyle.
“What makes our research design unique is that sedentary time and physical activity of both groups were measured with accelerometers throughout the entire three-month period, whereas in earlier studies activity has typically been measured only for a few days at the beginning and end of the study period. This makes it possible to receive more information on the actual behaviour changes over a longer time period,” explained Doctoral Candidate Taru Garthwaite from the University of Turku in Finland.
The intervention group reduced sedentary time by 50 minutes per day on average, mainly by increasing the amount of light- and moderate-intensity physical activity. Over the three-month period, the researchers observed benefits in health outcomes related to blood sugar regulation, insulin sensitivity and liver health in the intervention group.
“It is an encouraging thought that health benefits can be achieved by reducing the time spent sitting and increasing the amount of even light-intensity physical activity. For many, this may be an easier starting point than increasing actual exercise,” said Garthwaite.
People who do not meet the weekly physical activity recommendations atre the most likely to benefit the most from replacing sedentary time with light physical activity. However, reducing sedentary time is probably not enough in itself to prevent diseases if the person has several risk factors of diabetes and cardiovascular diseases.
Garthwaite stressed the encouraging nature of the findings: “Reducing the time spent sitting might still slow down the development of these diseases, but greater benefits can of course be gained by increasing the amount or intensity of physical activity in addition to sitting less.”
The researchers next aim to study how changes in daily activity and sedentary time affect energy metabolism and body composition in addition to the risk factors of diabetes and cardiovascular diseases over a six-month study period.
In infants treated with antibiotics, fungal gut microbiota are more abundant and diverse compared with the control group even six weeks following the start of the antibiotic course, according to a study published in the Journal of Fungi. The study’s authors suggest that reduced competition from gut bacteria being killed by antibiotics left more space for fungi to multiply.
“The results of our research strongly indicate that bacteria in the gut regulate the fungal microbiota and keep it under control. When bacteria are disrupted by antibiotics, fungi, Candida in particular, have the chance to reproduce,” explained PhD student Rebecka Ventin-Holmberg from the University of Helsinki.
A new key finding in the study was that the changes in the fungal gut microbiota, together with the bacterial microbiota, may be partly responsible for the long-term adverse effects of antibiotics on human health.
Antibiotics are the most commonly prescribed drugs for infants, causing changes in the gut microbiota at its most important developmental stage. These changes are more long-term compared to those in adults.
“Antibiotics can have adverse effects on both the bacterial and the fungal microbiota, which can result in, for example, antibiotic-associated diarrhoea,” Ventin-Holmberg said.
“In addition, antibiotics increase the risk of developing chronic inflammatory diseases, such as inflammatory bowel disease (IBD), and they have been found also to have a link to overweight,” she added.
These long-term effects are thought to be caused, at least in part, by an imbalance in the gut microbiota.
This study involved infants with a respiratory syncytial virus (RSV) infection who had never previously received antibiotics. While some of the children were given antibiotics due to complications, others received no antibiotic therapy throughout the study.
“Investigating the effects of antibiotics is important for the development of techniques that can be used to avoid chronic inflammatory diseases and other disruptions to the gut microbiota in the future,” Ventin-Holmberg emphasised.
While there have been many studies on the effect of antibiotics on bacterial microbiota, there has been a lack of studies on fungal microbiota. This study’s findings indicate that fungal microbiota may also have a role in the long-term effects of imbalance in the gut microbiota.
“Consequently, future research should focus on all micro-organisms in the gut together to better understand their interconnections and to obtain a better overview of the microbiome as a whole,” Ventin-Holmberg noted.
The US Supreme Court has voted to strike down the landmark Roe v Wade decision which constitutionally protects abortion rights, according to an initial draft majority opinion leaked by news outlet POLITICO. This comes at a time when abortion rights are being challenged in a number of US states, and such a ruling would cause abortion to become immediately illegal in 22 US states.
In 2019, there were 630 000 reported abortions in the US in 2019, according to the US Centers for Disease Control, an 18% decrease compared with 2010. Women in their 20s accounted for 57% of abortions in 2019. Abortions are highest among black American women, with a rate of 27 per 1000 for ages 15–44.
The Roe v Wade decision in 1973 gave women in the US an absolute right to an abortion in the first three months of pregnancy, and limited rights in the second trimester.
In 1992, in Planned Parenthood v Casey, it was ruled that states could not place an “undue burden” on women seeking abortions before a foetus could survive outside the womb, at about 24 weeks.
The draft opinion written by Justice Samuel Alito completely refutes the 1973 decision which guaranteed constitutional protections of abortion rights in the US, and also a subsequent 1992 decision – Planned Parenthood v. Casey – that largely maintained the right. “Roe was egregiously wrong from the start,” Justice Alito wrote.
“We hold that Roe and Casey must be overruled,” he writes in the document, labelled as the “Opinion of the Court.” “It is time to heed the Constitution and return the issue of abortion to the people’s elected representatives.”
In the past, deliberations on controversial cases have been fluid, with justices occasionally changing their votes as draft opinions circulate. This represents a rare breach of Supreme Court secrecy and tradition around its deliberations. The final, binding decision, is expected to be published in two months. Currently, five Republican appointees including Justice Alito have voted in favour of repealing Roe and Casey, while the three Democrat appointees are dissenting. It is not known how the last member, Chief Justice John Roberts, will vote.
The ruling as it currently stands would end the 49 year old US constitutional protection of abortion rights, instead allowing each US state to restrict or ban abortions outright.
POLITICO notes that public disclosure of a draft decision is unprecedented in the court’s modern history. Some observers had predicted that the conservative majority would have chipped away at abortion rights without overturning it.
The draft shows that the court is seeking to reject Roe’s logic and legal protections. “The inescapable conclusion is that a right to abortion is not deeply rooted in the Nation’s history and traditions,” Justice Alito wrote, declaring that one Roe’s central tenets, the “viability” distinction between foetuses not capable of surviving outside the uterus and those which can, “makes no sense.”
Justice Alito also described doctors and nurses who terminate pregnancies as “abortionists”, instead of the more neutral term “abortion providers” used by Chief Justice Roberts.
Carbon monoxide (CO) is an odourless and colourless gas is produced from incomplete burning, and is a silent killer, binding to haemoglobin with few treatments available other than administering oxygen. Now, research published in Chemical Communications suggests a path to a possible antidote.
In the US, more than 400 deaths and 20 000 emergency room visits are attributable to carbon monoxide (CO) poisoning every year. While CO detectors and making sure fireplace and heaters work correctly can help prevent exposure, there are limited treatment options for those suffering from CO poisoning.
To address this, Tim Johnstone, an assistant professor of chemistry and biochemistry at UC Santa Cruz, has been working to develop an easy-to-administer antidote.
“If you are exposed to carbon monoxide, the primary treatment right now is fresh air,” said A/Prof Johnstone. “It is a question of time. In fresh air, you need four to six hours for the level of CO in your blood to be cut in half. With 100 percent oxygen or hyperbaric oxygen, the half-life shortens further. Even then, the high blood levels of CO can persist long enough to lead to long-term deficits and neurological problems.”
A/Prof Johnstone has been studying the chemistry of carbon monoxide. In a biological context, CO binds to metal centres such as the iron in haemoglobin, preventing this protein from carrying out its oxygen carrying function.
To mitigate this, A/Prof Johnstone has designed small molecules that possess many of the features of the active site of haemoglobin but can bind CO much more tightly than the protein. In his most recent study, his group described the ability of one such molecule to bind CO, sequester CO that is already bonded to haemoglobin, and rescue red blood cells exposed to CO: all promising signs for a future antidote.
These are early results, said A/Prof Johnstone, but the hope is to create a point-of-care treatment that can be administered quickly. The most common carbon monoxide poisoning symptoms are headache, dizziness, weakness, upset stomach, vomiting, chest pain, and confusion. Because it mimics the flu, people may experience symptoms without realizing the danger and delay seeking treatment.
Investigating the state of affairs in public clinics, Spotlight’s Daniel Steyn and Vusi Mokoena investigate whether the right technology could help them out of their predicament.
“I never look forward to clinic day,” says Nomtsato Tsietsi, 74, on a Monday morning while standing in the queue at Kayamandi Clinic in Stellenbosch, which she visits up to three times a month to collect pills, consult with a doctor, and have her blood tests taken.
Tsietsi has several diseases including diabetes and hypertension (high blood pressure). “We sit there for too long, sometimes all day,” she says.
Her experience is typical for people visiting state clinics. But for about 80% of South Africans, this is the only option: for most people private healthcare is unaffordable and public clinic services are free.
Some patients in the Kayamandi clinic queue said they sometimes pay people up to R80 to stand in the queue for them. One man, who had been paid by someone to stand in the queue, said that he had been there since 5am.
For employed people, a day at the clinic typically means taking a day off work, often without pay.
The pubIic health system is beset with problems: long waiting times, insufficient record keeping, poorly maintained infrastructure, and poor service delivery.
A 2018 study of nurses and doctors in Cape Town found that of 16 essential skills, ten were not performed in more than half of the consultations. In more than 60% of consultations, nurses and doctors in Cape Town did not greet patients, and in 90% of consultations, they did not attempt to understand the patient’s perspective. In nother study, 76% of Cape Town-based doctors in primary care reported that they are suffering from burnout.
During our visit to Kayamandi Clinic, we asked patients whether they would embrace technological solutions to make the experience more efficient. They all said they would. Almost all of them are smartphone users and some said they could not understand why appointments cannot be made and managed digitally, or why they cannot communicate with health workers online rather than in person.
Innovative technology solutions for primary care exist in South Africa.Phukulisa Health Solutions, for example, offers a platform that mimics a consultation with a healthcare practitioner. Equipped with Bluetooth sensors, the platform can screen patients for a range of health issues, focused specifically on HIV, TB, diabetes, and heart diseases.
Phukulisa’s CEO Raymond Campbell says that this testing and screening platform offers a more efficient screening service with a faster turnaround time. For example, the platform has been tested at an antenatal unit in Mamelodi, where the platform provided test results within 14 minutes, opposed to the usual 23 hours.
But Campbell says there is little interest from the public sector in his technology. Instead, he is finding more success licensing the platform to players in the private sector.
There have been some attempts to use innovative computer technology in public sector clinics. In Limpopo, the deputy director-general of the health department, Dr Muthei Dombo, has the vision to create a “clinic in the cloud”.
In 2018, Dombo partnered with theMint Group to conduct a trial funded by Microsoft at Rethabile clinic. Dombo provided the team at Mint Group with several problems to solve.
The team, led by Peter Reid, developed a technology to alleviate the high rate of fraud at medicine dispensing points, the difficulty of transferring medical records between different clinics, and the long waiting times.
When a patient entered the clinic, they would register at reception. Their identity document would be scanned and a picture would be taken of the patient. At every station in the clinic visited by the patient, a camera would identify the patient and the patient’s records would pop up on the screen. When the patient left the station, the profile would automatically lock.
This ensured that only patients due for specific medication would receive that medication, thereby eliminating fraud. Because the records were all kept in the cloud, the records could easily be transferred to another clinic. Without this technology, patients need to return to the same clinic every time they need to restock their medication.
The trial also assisted with queue management. Upon entering the clinic, patients would choose a “journey” based on their reason for visiting the clinic. The system would then guide the patient from one station to the next on big screens on the wall. This made the journey more seamless while also providing visual feedback to officials at the clinic helping them to manage the queues more effectively.
The trial ended shortly before the start of the Covid pandemic. The project has not yet been restarted.
One project that has been implemented widely in the public sector is Vula Mobile. Founded by Dr William Mapham in 2014, Vula aims to bridge the gap between health workers and specialists.
There is a shortage of specialist doctors in the public sector and health workers at the primary care level often lack the information to refer patients to a relevant specialist.
With the Vula app, a nurse seeing a patient can be linked with the closest specialist. Through the built-in chat function, the nurse can provide the specialist with all the necessary info and refer the patient.
The app is available in six provinces with an emphasis on the Eastern Cape. More than 24,000 health workers are registered on the system.
But other innovators in the health space, frustrated by the public sector, are focusing on providing affordable private healthcare. This follows a growing trend in South Africa, as medical aid providers increasingly offer more affordable packages targeted to lower-income earners.
At the Kayamandi clinic during GroundUp’s visit, Mcoleseli Mlenze, a 34-year-old father who often visits the clinic for hypertension medication or when his son is sick, said that while he uses the clinic to collect medication, he has started seeing a private doctor when he is sick.
He says he cannot really afford the private doctor, which costs upwards of R350 per consultation. If there was some middle-ground where he could pay R150-R200 for a consultation at a clinic that is faster and more efficient, he would happily do so.
Others in the queue said they would pay up to R50 for a better healthcare experience.
Saul Kornik, the founder of Healthforce and the Kena App, aims to lower the cost of quality primary health care so that millions of people have access to it.
Available in almost 500 pharmacies throughout the country, Healthforce’s technology enables nurses to conduct all necessary screenings and diagnostic procedures. If and when a doctor becomes necessary, the nurse presses a button to start a video call with one of the doctors in the Healthforce network.
The nurse and patient can both see the doctor and the doctor, with the help of the nurse, can consult the patient. This reduces the amount of time that the doctor is needed, thereby reducing the cost.
The patient ends up paying on average R70 to R90 for the nurse and R115 to R250 for the doctor. If needed, the doctor can prescribe medication that the patient can purchase at the pharmacy or pick up from a government dispensary.
There are Healthforce doctors available to speak any of the 11 official languages and they are available seven days a week.
In March, Healthforce launched the Kena Health app, through which patients can have consultations with nurses, doctors and mental health practitioners via chat, voice or video. The first three consultations per year are free.
After the consultation, if necessary, the doctor can provide a script for medication and a sick note.
At Kayamandi clinic, Gcobisa Malithafa, a 30-year-old mother of a toddler told GroundUp that although she would pay a small amount for a better experience, it should not have to come to that.
Malithafa suggests that instead, the clinic’s management should consult the community on a regular basis and make immediate improvements to the running of the clinic. “This thing of having one doctor at the clinic is not right,” she says.
She is struggling to get her child immunised, having visited the clinic many times without success.
Whether they use technology or not, she says, something has to change.
Despite the greater safety and efficacy of a new short course treatment for HIV-related cryptococcal meningitis (CM), access to the treatment in South Africa will be a challenge, according to a pair of articles by Spotlight.
Following positive results of a trial, the World Health Organization last week announced new recommendations for the treatment of CM, with a single high dose of L-AmB followed by two weeks of flucytosine and fluconazole.
Using L-AmB (AmBisome) and flucytosine for the treatment of CM will be a welcome change for South Africa, which has the world’s highest burden of the condition. This shorter course with fewer side effects than the current treatment involving amphotericin-B could save lives as well as clinical resources in the public sector, but at present the treatment is hamstrung by pricing and availability uncertainty, with a course of L-AmB currently only available at a steep cost.
“Amphotericin B [deoxycholate] is a drug that doctors and nurses used to call ampho-terrible,” Amir Shroufi, Médecins Sans Frontières (MSF) Southern Africa board member told Spotlight.
He explained that “it’s a really nasty drug, doctors and nurses don’t like it because it can cause severe anaemia. It’s toxic to the kidneys, so it can cause kidney damage and even kidney failure… and the infusion line used for the drug can often become infected and it can cause inflammation of the veins where it’s going into the body.”
L-AmB is a “much better drug”, he said, with great benefits of administering it for one day as opposed to a week or two. The seriousness of CM meant hospitalisation will still be required, pointed out Dr Jacqui Miot, division director of the Wits Health Economics and Epidemiology Research office, but means that patients won’t be tethered to a drip and may be able to go home sooner.
Under the treatment regimen, a patient receives a single high dose of L-AmB on the first day of treatment, followed by a 14-day course of flucytosine and fluconazole pills.
For a 60kg patient at the recommended dosage, twelve 50mg vials of L-AmB are needed, which at Gilead’s promised access price would be R2 880. Key Oncologics’ currently charges R34 560 for 12 vials.
Even given the availability of L-AmB, Shrouifi warns that “whatever you’re doing, you have to have flucytosine. That’s your baseline, even if you’re giving liposomal amphotericin B, you have to have the flucytosine”.
Flucytosine is an old, off-patent medicine developed in the 1950s. Despite its age and its demonstrated efficacy in the landmark ACTA trial four years ago, flucytosine was only recently authorised for use in South Africa and is only slowly being rolled out.
Amir Shroufi warned that access to the life-saving medicine remains a major issue. “Doctors are not being given the tools they need to treat [CM],” he said. “The first tool they have to have is flucytosine and they still don’t have flucytosine. So, that’s the thing that needs to happen urgently, you know, tomorrow! Everyone with cryptococcal meningitis must get access to flucytosine.”
Like L-AmB, Mylan’s 250mg and 500mg flucytosine tablets were only registered recently, in December 2021. The Department of Health’s target price for a pack of 100 tablets is R1 500. Fortunately, it appears that the Clinton Health Access Initiative (CHAI) will be able to secure packs of 100 at R1 470 each for use in South Africa’s flucytosine access programme.
The next steps for rollout of flucytosine will be inclusion on the national essential medicines list and in CM treatment guidelines before tenders can be put out.
For patients with painful finger osteoarthritis, lipofilling a nonsurgical procedure where a patient’s fat is transferred into the arthritic joints, may result in lasting improvements in hand function and especially pain, according to a study in Plastic and Reconstructive Surgery.
Researchers reported their experience with 18 patients undergoing fat transfer procedures for finger osteoarthritis.
“Even over a long-term follow-up, the transfer of fatty tissue to arthritic fingers joints appears to provide a safe and minimally invasive alternative to conventional surgery for patients with osteoarthritis,” commented the study’s lead author Max Meyer-Marcotty, MD, PhD.
In the lipofilling procedure, a sample of the patient’s own fatty tissue was obtained by liposuction from another part of the body: the upper thigh or hip area. Tiny volumes of lipid cells (< 1mL) were injected into the arthritic finger joints. For recovery, patients wore a splint around the treated finger and took pain relievers for a week. No infections or other complications were recorded.
The researchers analysed follow-up outcomes in a total of 25 finger joints treated by lipofilling. Hand function, pain scores, and patient satisfaction were evaluated an average of 44 months (maximum 50 months) after treatment.
Assessment showed a “highly significant clear improvement” in pain score: from a median of 6 points (on a 10-point scale) before treatment to 0.5 points at follow-up. “We believe that for our patients the reduction of pain represents the most striking and important result, which also has the most pronounced and highly significant effect,” Dr Meyer-Marcotty et al. wrote.
On functional evaluation, pinch grip strength of the treated fingers increased from a median of 2.0kg before lipofilling to 4.3kg at follow-up. Non-significant improvements were seen in fist closure force and score on a standard assessment of hand function during everyday tasks.
In severe cases of osteoarthritis, surgery is effective in relieving arthritis pain, but is associated with potential complications and lengthy recovery time.
Fat transfer procedures have been introduced in recent years for a growing range of purposes in plastic and reconstructive surgery. Animal studies have suggested that mesenchymal stromal cells found in fatty tissues can regenerate tissue in arthritic joints.
“The chance to preserve the joint with a minimally invasive procedure is of particular interest in the early, albeit painful, phases of finger osteoarthritis,” Dr. Meyer-Marcotty added. “Since the lipofilling procedure is nondestructive, conventional joint surgery can still be performed later, if needed.”
Larger long-term follow-up studies are needed to further corroborate these initial positive findings, the researchers said.
According to research published in Nature Aging, seven hours is the ideal amount of sleep for people in their middle age and upwards, with too little or too much little sleep associated with poorer cognitive performance and mental health.
Sleep plays an important role in enabling cognitive function and maintaining good psychological health, and also removes waste products from the brain. Alterations in sleep patterns appear during ageing, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the ageing population.
Scientists from the UK and China examined data from nearly 500 000 adults aged 38–73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40 000 of the study participants.
The researchers found in their analysis that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. The optimal amount of sleep was found to be seven hours per night for cognitive performance and good mental health. More symptoms of anxiety and depression and worse overall wellbeing were associated with sleeping for longer or shorter durations.
The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave — ‘deep’ — sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid — a key protein which, when it misfolds, can cause ‘tangles’ in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain’s ability to rid itself of toxins.
The amount of sleep was also linked differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.
Consistently getting seven hours’ sleep each night was also important to cognitive performance and good mental health and wellbeing. Interrupted sleep patterns have previously been shown to be associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.
Professor Jianfeng Feng from Fudan University in China said: “While we can’t say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains.”
The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer’s disease and dementia, in which cognitive decline is a hallmark symptom.
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study’s authors, said: “Getting a good night’s sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias.”
New research published in Human Geneticsshows that people with blue eyes trace their ancestry back to a single individual. Researchers tracked down a genetic mutation which took place 6–10 000 years ago and is the cause of the eye colour of all blue-eyed humans without albinism alive on the planet today.
While blue eyes evolved only once, blonde hair has evolved at least twice: in Melanesian populations, blonde hair evolved independently to European populations, involving a mutation in a different gene.
“Originally, we all had brown eyes,” said Professor Hans Eiberg from the University of Copenhagen. “But a genetic mutation affecting the OCA2 gene in our chromosomes resulted in the creation of a ‘switch’, which literally ‘turned off’ the ability to produce brown eyes.” The OCA2 gene codes for the P protein, which is involved melanin production. This ‘switch’, located in the gene next to OCA2, does not completely shut off production but instead is limited to reducing the production of melanin in the iris, effectively ‘diluting’ brown eyes to blue. The switch’s effect on OCA2 is very specific therefore. If the OCA2 gene is completely destroyed or turned off, albinism would be the result.
Eye colours from brown to green depend on the amount of melanin in the iris, but blue-eyed individuals only have a small degree of variation in the amount of melanin in their eyes. “From this we can conclude that all blue-eyed individuals are linked to the same ancestor,” said Professor Eiberg. “They have all inherited the same switch at exactly the same spot in their DNA.” Brown-eyed individuals, by contrast, have considerable individual variation in the area of their DNA that controls melanin production.
Professor Eiberg and his team studied mitochondrial DNA and compared the eye colour of blue-eyed individuals in countries as diverse as Jordan, Denmark and Turkey. His research stretches back to 1996, when he first implicated the OCA2 gene as being responsible for eye colour.
The mutation of brown to blue eyes does not confer any evolutionary advantage, as with others such as hair colour.
As Professor Eiberg explained, “it simply shows that nature is constantly shuffling the human genome, creating a genetic cocktail of human chromosomes and trying out different changes as it does so.”
In a new study published in Nature, researchers found that treatments that were effective for atopic dermatitis (AD) in lean mice actually worsened the condition in obese mice.
Tracking the development of AD in obese and lean mice, the researchers found that obese mice developed more inflammation and more severe AD. This increased inflammation was present even after obese mice lost weight. There were similar results in an experimental model of asthma, with obese mice developing more inflammation.
The researchers next looked in detail at immune cells called T cells in lean and obese mice with AD. Lean mice had more TH2 cells, a class of T cells known to play a role in the development of AD. Obese mice had more of a class of T cells called TH17. These cells trigger a different type of inflammation.
Similar trends were seen in blood samples taken from people. Markers of TH17 cell activity increased along with body mass index (BMI) in a database of serum collected from people with AD. Conversely, in samples from patients with severe asthma, TH2 cell activity decreased as BMI increased.
Drugs that block TH2 cell activity are used in the treatment of severe AD as well as asthma and other inflammatory conditions. The researchers tested antibodies to block TH2 cell activity in lean and obese mice with severe AD. While the antibodies reduced skin inflammation in lean mice as expected, they made the condition worse in obese mice. Analysis of immune cells suggested that blocking TH2 cell activity in the obese mice worsened other forms of inflammation.
Obese mice were also found to have less activity of peroxisome proliferator-activated receptor-γ (PPARɣ) in their TH2 cells. When lean mice were engineered to lack PPARɣ, their inflammatory response resembled that of obese mice.
Drugs that increase PPARɣ activity increase insulin sensitivity and are approved for the treatment of type 2 diabetes. The researchers found that giving one of these drugs to obese mice changed their inflammatory response to resemble that of lean mice. It also restored their sensitivity to the antibodies that block TH2 cell activity.
“Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes,” said Dr Ronald Evans from the Salk Institute, who helped lead the work.
