Tag: obesity

Categories : Metabolic DisordersTags :

Why do Some People with Obesity Remain Healthy?

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Source: Pixabay CC0

Although obese individuals are at greater risk of diabetes, high blood pressure or high cholesterol, not all obese people develop metabolic diseases of this kind. With around a quarter of all obese individuals are healthy, scientists are trying to work out why some obese people become unhealthy while others do not.

Now, a comprehensive study by researchers from Zurich and Leipzig has provided a vital basis for this work. Specifically, the researchers have produced a detailed atlas with data from healthy and unhealthy overweight people, on their fat (adipose) tissue, and on the gene activity in this tissue’s cells. “Our results can be used to look for cellular markers that provide information on the risk of developing metabolic diseases,” explains Adhideb Ghosh, a researcher in ETH Professor Christian Wolfrum’s group and one of the two lead authors of the study. “The data is also of great interest for basic research. It could help us develop new therapies for metabolic diseases.”

The study appears in Cell Metabolism.

Investigating a large biobank

For this study, Ghosh and his colleagues used the Leipzig Obesity Biobank, an extensive collection of biopsies taken from obese individuals. Compiled by scientists from the University of Leipzig, these samples originate from obese patients who underwent elective surgery and consented to the collection of adipose tissue samples for research purposes. The collection also includes extensive medical information on the patients’ health.

Since the tissue samples were all taken from obese individuals with or without metabolic diseases, they allow comparison between individuals with healthy and unhealthy obesity. In samples from 70 volunteers, the researchers at ETH Zurich examined which genes were active, and to what extent, on a cell-by-cell basis for two types of adipose tissue: subcutaneous and visceral.

Scientists and medical experts assume that visceral fat, which lies deep in the abdominal cavity and surrounds the internal organs, is primarily responsible for metabolic diseases. By contrast, experts generally believe that fat located directly beneath the skin is less problematic.

For the study, it was vital that the adipose tissue cells were not all simply lumped together, as this tissue comprises not only fat cells (adipocytes) but also cells of other types. “In fact, the adipocytes are in the minority,” explains lead author Isabel Reinisch, a postdoc in Wolfrum’s group. A large part of adipose tissue is made up of immune cells, cells that form blood vessels, and immature precursor cells of adipocytes. Another cell type, known as mesothelial cells, are found only in visceral adipose tissue and mark its outer boundary.

Abdominal fat remodelled – and gender differences

As the researchers were able to show, there are significant functional changes in cells in the visceral adipose tissue of people with metabolic diseases. This remodelling affects almost every cell type in this form of tissue. For example, the genetic analyses showed that the adipocytes of unhealthy individuals could no longer burn fats as effectively and instead produced greater quantities of immunologic messenger molecules. “These substances trigger an immune response in the visceral fat of obese people,” explains Reinisch. “It’s conceivable that this response promotes the development of metabolic diseases.”

The researchers also found very clear differences in the number and function of mesothelial cells: in healthy obese individuals, there is a far greater proportion of mesothelial cells in the visceral fat and these cells exhibit greater functional flexibility. Specifically, the cells can switch into a sort of stem cell mode and therefore convert into different cell types, such as adipocytes, in healthy individuals. “The ability of fully differentiated cells to convert into stem cells is otherwise primarily associated with cancer,” says Reinisch. She was surprised, therefore, to find this ability in adipose tissue as well. “We suspect that the flexible cells at the edge of the adipose tissue in healthy obese individuals facilitate smooth tissue expansion.”

Finally, the researchers also found differences between men and women: a certain type of progenitor cell is present only in the visceral fat of women. “This could explain differences in the development of metabolic diseases between men and women,” says Reinisch.

Finding new biomarkers

The new atlas of gene activity in overweight people describes the composition of cell types in adipose tissue and their function. “However, we cannot say whether the differences are the reason why someone is metabolically healthy or whether, conversely, metabolic diseases cause these differences,” says Ghosh. Instead, the scientists view their work as providing the basis for further research. They have published all the data in a publicly accessible web app so that it is available for other researchers to work with.

In particular, this atlas now makes it possible to find new markers that provide information on the risk of developing a metabolic disease. At present, the ETH researchers are also looking for these kinds of markers, which could help to improve the treatment of such diseases. For example, there is a new class of drugs that suppress the appetite and promote insulin release in the pancreas – but these medications are in short supply. “Biomarkers that can be derived from our data could help to identify those patients who are most in need of this treatment,” says Reinisch.

Source: ETH Zurich

Categories : Diet and Nutrition Metabolic DisordersTags :

In Obesity or Not, Individuals Prefer High-calorie Food

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Calorie content drives food preference despite similar taste in individuals with and without obesity

Source: Pixabay CC0

Higher calorie foods were preferred among individuals with and without obesity despite similar taste and texture, according to a study published December 17th in the open-access journal PLOS Biology by Albino Oliveira-Maia from the Champalimaud Foundation, Portugal, and colleagues.

Eating sends signals to the brain with information about a food’s energy content, which can influence food preferences irrespective of flavor. People with obesity often have impairments in areas of the brain where dopamine is released, which may drive reward-related eating and a preference for energy-dense foods rich in fat and sugars. Weight loss due to bariatric surgery has been associated to a normalization of reward-related eating with a shift of preferences toward healthier options, but the underlying mechanisms are not well understood.

In this study, after examining a large group of healthy volunteers, researchers compared food preferences in three groups: 11 individuals with obesity, 23 post-bariatric surgery patients, and 27 non-obese control subjects. They gave participants sweetened low-fat yogurt with and without maltodextrin (a carbohydrate that adds calories to the yogurt with no impact on taste or texture). Participants ate the yogurt at home, alternating between the maltodextrin-containing and -free yogurt. All three groups ate more of the maltodextrin-containing yogurt, despite rating both as equally pleasant. Somewhat unexpectedly, the effects of maltodextrin on yogurt consumption were similar in individuals with obesity relative to their non-obese counterparts.

The study also used radioactive iodine labelling and single photon emission computed tomography to visualise dopamine receptors in the brain. Consistent with previous studies, individuals with obesity had lower dopamine receptor availability than non-obese controls. Dopamine receptor availability was similar in the surgical and non-obese groups and was associated with more restrained eating. These results suggest that obesity-related brain changes can be reversed after bariatric surgery, potentially impacting the amount of food consumed but not necessarily the types of food preferred.

The authors add, “We were very intrigued that, while behaviour was guided towards eating yoghurts with higher energy-content, this did not seem to be a result of explicit choices, since consistent changes in pleasantness of flavours enriched with carbohydrates were not found. Importantly, this behaviour was maintained in patients with obesity and after weight-loss surgery, even though there were important differences in their brain dopaminergic system.”

Provided by PLOS

Categories : General Interest Medical Research & TechnologyTags :

Healthcare Trends to Watch in 2025

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AI image made with Gencraft using Quicknews’ prompts.

Quicknews takes a look at some of the big events and concerns that defined healthcare 2024, and looks into its crystal ball identify to new trends and emerging opportunities from various news and opinion pieces. There’s a lot going on right now: the battle to make universal healthcare a reality for South Africans, growing noncommunicable diseases and new technologies and treatments – plus some hope in the fight against HIV and certain other diseases.

1. The uncertainty over NHI will continue

For South Africa, the biggest event in healthcare was the signing into law of the National Health Insurance (NHI) by President Ramaphosa in May 2024, right before the elections. This occurred in the face of stiff opposition from many healthcare associations. It has since been bogged down in legal battles, with a section governing the Certificate of Need to practice recently struck down by the High Court as it infringed on at least six constitutional rights.

Much uncertainty around the NHI has been expressed by various organisation such as the Health Funders Association (HFA). Potential pitfalls and also benefits and opportunities have been highlighted. But the biggest obstacle of all is the sheer cost of the project, estimated at some R1.3 trillion. This would need massive tax increases to fund it – an unworkable solution which would see an extra R37 000 in payroll tax. Modest economic growth of around 1.5% is expected for South Africa in 2025, but is nowhere near creating enough surplus wealth to match the national healthcare of a country like Japan. And yet, amidst all the uncertainty, the healthcare sector is expected to do well in 2025.

Whether the Government of National Unity (GNU) will be able to hammer out a workable path forward for NHI remains an open question, with various parties at loggerheads over its implementation. Public–private partnerships are preferred by the DA and groups such as Solidarity, but whether the fragile GNU will last long enough for a compromise remains anybody’s guess.

It is reported that latest NHI proposal from the ANC includes forcing medical aid schemes to lower their prices by competing with government – although Health Minister Aaron Motsoaledi has dismissed these reports. In any case, medical aid schemes are already increasing their rates as healthcare costs continue to rise in what is an inexorable global trend – fuelled in large part by ageing populations and increases in noncommunicable diseases.

2. New obesity treatments will be developed

Non-communicable diseases account for 56% of deaths in South Africa, and obesity is a major risk factor, along with hypertension and hyperglycaemia, which are often comorbid. GLP-1 agonists were all over the news in 2023 and 2024 as they became approved in certain countries for the treatment of obesity. But in South Africa, they are only approved for use in obesity with a diabetes diagnosis, after diet and exercise have failed to make a difference, with one exception. Doctors also caution against using them as a ‘silver bullet’. Some are calling for cost reductions as they can be quite expensive; a generic for liraglutide in SA is expected in the next few years.

Further on the horizon, there are a host of experimental drugs undergoing testing for obesity treatment, according to a review published in Nature. While GLP-1 remains a target for many new drugs, others focus on gut hormones involved in appetite: GIP-1, glucagon, PYY and amylin. There are 5 new drugs in Phase 3 trials, expected variously to finish between 2025 and 2027, 10 drugs in Phase 2 clinical trials and 18 in Phase 1. Some are also finding applications beside obesity. The GLP-1 agonist survodutide, for example have received FDA approval not for obesity but for liver fibrosis.

With steadily increasing rates of overweight/obesity and disorders associated with them, this will continue to be a prominent research area. In the US, where the health costs of poor diet match what consumers spend on groceries, ‘food as medicine’ has become a major buzzword as companies strive to deliver healthy nutritional solutions. Retailers are providing much of the push, and South Africa is no exception. Medical aid scheme benefits are giving way to initiatives such as Pick n Pay’s Live Well Club, which simply offers triple Smart Shopper points to members who sign up.

Another promising approach to the obesity fight is precision medicine, which factors in many data about the patient to identify the best interventions. This could include detailed study of energy balance regulation, helping to select the right antiobesity medication based on actionable behavioural and phsyiologic traits. Genotyping, multi-omics, and big data analysis are growing fields that might also uncover additional signatures or phenotypes better responsive to certain interventions.

3. AI tools become the norm

Wearable health monitoring technology has gone from the lab to commonly available consumer products. Continued innovation in this field will lead to cheaper, more accurate devices with greater functionality. Smart rings, microneedle patches and even health monitoring using Bluetooth earphones such as Apple’s Airpods show how these devices are becoming smaller and more discrete. But health insurance schemes remain unconvinced as to their benefits.

After making a huge splash in 2024 as it rapidly evolved, AI technology is now maturing and entering a consolidation phase. Already, its use has become commonplace in many areas: the image at the top of the article is AI-generated, although it took a few attempts with the doctors exhibiting polydactyly and AI choosing to write “20215” instead of “2025”. An emerging area is to use AI in patient phenotyping (classifying patients based on biological, behavioural, or genetic attributes) and digital twins (virtual simulations of individual patients), enabling precision medicine. Digital twins for example, can serve as a “placebo” in a trial of a new treatment, as is being investigated in ALS research.

Rather than replacing human doctors, it is likely that AI’s key application is reducing lowering workforce costs, a major component of healthcare costs. Chatbots, for example, could engage with patients and help them navigate the healthcare system. Other AI application include tools to speed up and improve diagnosis, eg in radiology, and aiding communication within the healthcare system by helping come up with and structure notes.

4. Emerging solutions to labour shortages

Given the long lead times to recruit and train healthcare workers, 2025 will not likely see any change to the massive shortages of all positions from nurses to specialists.

At the same time, public healthcare has seen freezes on hiring resulting in the paradoxical situation of unemployed junior doctors in a country desperately in need of more doctors – 800 at the start of 2024 were without posts. The DA has tabled a Bill to amend the Health Professions Act at would allow private healthcare to recruit interns and those doing community service. Critics have pointed out that it would exacerbate the existing public–private healthcare gap.

But there are some welcome developments: thanks to a five-year plan from the Department of Health, family physicians in SA are finally going to get their chance to shine and address many problems in healthcare delivery. These ‘super generalists’ are equipped with a four-year specialisation and are set to take up roles as clinical managers, leading multi-disciplinary district hospital teams.

Less obvious is where the country will be able to secure enough nurses to meet its needs. The main challenge is that nurses, especially specialist nurses, are ageing – and it’s not clear where their replacements are coming from. In the next 15 years, some 48% of the country’s nurses are set to retire. Coupled with that is the general consensus that the new nursing training curriculum is a flop: the old one, from 1987 to 2020, produced nurses with well-rounded skills, says Simon Hlungwani, president of the Democratic Nursing Organisation of South Africa (Denosa). There’s also a skills bottleneck: institutions like Baragwanath used to cater for 300 students at a time, now they are only approved to handle 80. The drive for recruitment will also have to be accompanied by some serious educational reform to get back on track.

5. Progress against many diseases

Sub-Saharan Africa continues to drive declines in new HIV infections.  Lifetime odds of getting HIV have fallen by 60% since the 1995 peak. It also saw the largest decrease in population without a suppressed level of HIV (PUV), from 19.7 million people in 2003 to 11.3 million people in 2021. While there is a slowing in the increase of population living with HIV, it is predicted to peak by 2039 at 44.4 million people globally. But the UNAIDS HIV targets for 2030 are unlikely to be met.

As human papillomavirus (HPV) vaccination programmes continue, cervical cancer deaths in young women are plummeting, a trend which is certain to continue.

A ‘new’ respiratory virus currently circulating in China will fortunately not be the next COVID. Unlike SARS-CoV-2, human metapneumovirus (HMPV) has been around for decades, and only causes a few days of mild illness, with bed rest and fluids as the primary treatment. The virus has limited pandemic potential, according to experts.

Categories : Cancer PaediatricsTags :

Does Obesity Affect Children’s Chances of Survival after Cancer Diagnosis?

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Photo by Patrick Fore on Unsplash

A recent population-based study indicates that among children with cancer, those with obesity at the time of diagnosis may face an elevated risk of dying. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

The retrospective study was based on information from the Cancer in Young People in Canada (CYP-C) database, including all children with newly diagnosed cancer aged 2 to 18 years across Canada from 2001 to 2020. Obesity was defined as age and sex-adjusted body mass index at or above the 95th percentile.

Among 11 291 children with cancer, 10.5% were obese at the time of diagnosis. Investigators assessed 5-year event-free survival (survival free of cancer relapse), as well as overall survival.

Compared with patients without obesity at the time of initial cancer diagnosis, those with obesity had lower rates of 5-year event-free survival (77.5% versus 79.6%) and overall survival (83.0% versus 85.9%).

After adjusting for factors including age, sex, ethnicity, neighbourhood income quintile, treatment era, and cancer categories, obesity at diagnosis was linked with a 16% increase in the risk of relapse and a 29% increase in the risk of death. The negative impact of obesity on prognosis was especially pronounced in patients with acute lymphoblastic leukaemia and brain tumours.

“Our study highlights the negative impact of obesity among all types of childhood cancers. It provides the rationale to evaluate different strategies to mitigate the adverse risk of obesity on cancer outcomes in future trials,” said co–senior author Thai Hoa Tran, MD, of the Centre Hospitalier Universitaire Sainte-Justine, in Montreal. “It also reinforces the urgent need to reduce the epidemic of childhood obesity as it can result in significant health consequences.”

Source: Wiley

Categories : Cancer Surgeries & ProceduresTags :

Can Metabolic-bariatric Surgery help Prevent Pancreatic Cancer in Obesity?

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Sleeve gastrectomy. Credit: Scientific Animations CC4.0

Obesity and type 2 diabetes are risk factors for various malignancies, including pancreatic cancer, which has a high death rate. A new analysis in Diabetes/Metabolism Research and Reviews suggests that metabolic-bariatric surgery may lower the risk of developing pancreatic cancer in people with obesity, especially in those who also have type 2 diabetes.

In the systematic review and meta-analysis, investigators identified 12 relevant studies that explored the effects of metabolic-bariatric surgery on pancreatic cancer incidence, with a total of 3 711 243 adults with obesity. Surgery was associated with a 44% reduction in pancreatic cancer risk among individuals with obesity but without type 2 diabetes and a 79% risk reduction in those with both obesity and type 2 diabetes.

“Metabolic-bariatric surgery not only has beneficial effects on obesity and type 2 diabetes but also may play a crucial role in reducing the risk of pancreatic cancer in these individuals,” said corresponding author Angeliki M. Angelidi, PhD, of the Broad Institute of MIT and Harvard. “These findings underscore the need for further research to elucidate the underlying mechanisms and understand the full spectrum of health benefits of metabolic-bariatric surgery beyond weight loss.”

Source: Wiley

Categories : Cancer Metabolic DisordersTags :

The Outcomes of Cancer Therapies and BMI Have a Complex Relationship

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Risk of mortality during cancer treatment in relation to BMI. For non-small cell lung cancer treatment, immunotherapy seems to pose less risk for persons under a certain BMI, while conventional chemotherapy appears optimal for persons who might be overweight or obese. Credit: Osaka Metropolitan University

While being overweight increases the risk of developing lifestyle-related diseases, there is a phenomenon known as the obesity paradox where a decreased risk of death has been seen during cancer therapy. However, that paradox might not hold true for all cancer therapies, an Osaka Metropolitan University team reports in JAMA Network Open, a publication of the American Medical Association.

Led by graduate student Mr Yasutaka Ihara and Professor Ayumi Shintani of the Graduate School of Medicine’s Department of Medical Statistics, the team used a Japanese administrative claims database of more than 500 000 lung cancer patients and examined the relation between body mass index (BMI) and the risk of mortality during immunotherapy and conventional chemotherapy.

Focusing only on patients with advanced non-small cell lung cancer, the team found that the higher the BMI, the lower the risk of mortality when undergoing both immunotherapy and chemotherapy, though it does a U-turn around a BMI of 24. Patients with a BMI under 28 showed lower risk of mortality when undergoing immunotherapy compared to conventional chemotherapy, but for those at or over that figure, the risk increases with immunotherapy while it continues to get lower with chemotherapy.

“Immunotherapy might not always be the optimal treatment method for obese patients with advanced non-small cell lung cancer, so the use of conventional chemotherapy should also be considered,” Mr. Ihara stated. “In addition to BMI, age, hormones, and gut microbiota have been reported as factors that influence the effectiveness of immunotherapy. Evaluation of whether immunotherapy or conventional chemotherapy improves survival in the presence of these factors is expected to contribute to the development of precision medicine.”

Source: Osaka Metropolitan University

Categories : Metabolic Disorders OphthalmologyTags :

Study Reveals Association Between Semaglutide Use and Optic Neuropathy

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Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers from Mass Eye and Ear have discovered an association between semaglutide use and an increased risk of nonarteritic anterior ischaemic optic neuropathy (NAION) in patients with type 2 diabetes, overweight or obesity. The findings, which appear in JAMA Ophthalmology, only show an association and cannot establish causation.

Though NAION is relatively rare, occurring in in about 10 in 100 000, it is the second most common cause of optic nerve blindness, behind glaucoma, and it is the most common cause of sudden optic nerve blindness. Caused by decreased blood flow to the optic disc, it usually affects only one eye but in 15% of cases both eyes are involved. There are no treatments for this disease and little prospect for improvement, although it is painless.

The study was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School.

In mid-2023 Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend – three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. They did notice however that all three were taking semaglutide.

“The use of these drugs has exploded throughout industrialised countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, corresponding author of the study. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

This prompted the Mass Eye and Ear research team to run a retrospective analysis of their patient population to see if they could identify a link between this disease and these drugs.

They performed matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–GLP-1 receptor agonist medications for diabetes or obesity.

The researchers found that patients with diabetes who were prescribed and took semaglutide were four times (hazard ratio [HR], 4.28) more likely to be receive a NAION diagnosis. The odds increased to more than seven times (HR, 7.64) when the prescription was for weight control in obesity.

The researchers analysed the records of more than 17 000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analysed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

Study limitations include the fact that Mass Eye and Ear sees an unusually high number of people with rare eye diseases, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. Medication adherence could also not be assessed.

Only correlation can be shown by the study, not causality. How or why this association exists remains unknown. Likewise, the reason for the reported difference between diabetic and overweight groups – but this does not appear to result from a difference in baseline characteristics. The optic nerve is known to host GLP-1 receptors, but the study did not adequately address all the confounding factors. They also caution against generalising the results (from a majority white population) since Black individuals have a lower risk of NAION.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is pre-existing significant visual loss from other causes.”

Categories : Mental Health Obstetrics & GynaecologyTags :

Genetic Study Points to Oxytocin as Possible Treatment for Obesity and Postnatal Depression

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Photo by Patrick Fore on Unsplash

Scientists have identified a gene which, when missing or impaired, can cause obesity, behavioural problems and, in mothers, postnatal depression. The discovery, reported on 2 July in Cell, may have wider implications for the treatment of postnatal depression, with a study in mice suggesting that oxytocin may alleviate symptoms.

Obesity and postnatal depression are significant global health problems. Postnatal depression affects more than one in 10 women within a year of giving birth and is linked to an increased risk of suicide, which accounts for as many as one in five maternal deaths in high income countries. Meanwhile, obesity has more than doubled in adults since 1990 and quadrupled in adolescents, according to the World Health Organization.

While investigating two boys from different families with severe obesity, anxiety, autism, and behavioural problems triggered by sounds or smells, a team led by scientists at the University of Cambridge, UK, and Baylor College of Medicine, Houston, USA, discovered that the boys were missing a single gene, known as TRPC5, which sits on the X chromosome.

Further investigation revealed that both boys inherited the gene deletion from their mothers, who were missing the gene on one of their X chromosomes. The mothers also had obesity, but in addition had experienced postnatal depression.

To test if it was the TRPC5 gene that was causing the problems in the boys and their mothers, the researchers turned to animal models, genetically-engineering mice with a defective version of the gene (Trpc5 in mice).

Male mice with this defective gene displayed the same problems as the boys, including weight gain, anxiety, a dislike of social interactions, and aggressive behaviour. Female mice displayed the same behaviours, but when they became mothers, they also displayed depressive behaviour and impaired maternal care. Interestingly, male mice and female mice who were not mothers but carried the mutation did not show depression-like behaviour.

Dr Yong Xu, Associate Director for Basic Sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine, said: “What we saw in those mice was quite remarkable. They displayed very similar behaviours to those seen in people missing the TRPC5 gene, which in mothers included signs of depression and a difficulty caring for their babies. This shows us that this gene is causing these behaviours.”

TRPC5 is one of a family of genes that are involved in detecting sensory signals, such as heat, taste and touch. This particular gene acts on a pathway in the hypothalamus region of the brain, where it is known to control appetite.

When the researchers looked in more detail at this brain region, they discovered that TRPC5 acts on oxytocin neurons – nerve cells that produce the hormone oxytocin, often nicknamed the ‘love hormone’ because of its release in response to displays of affection, emotion and bonding.

Deleting the gene from these oxytocin neurons led to otherwise healthy mice showing similar signs of anxiety, overeating and impaired sociability, and, in the case of mothers, postnatal depression. Restoring the gene in these neurons reduced body weight and symptoms of anxiety and postnatal depression.

In addition to acting on oxytocin neurons, the team showed that TRPC5 also acts on so-called POMC neurons, which have been known for some time to play an important role in regulating weight. Children in whom the POMC gene is not working properly often have an insatiable appetite and gain weight from an early age.

Professor Sadaf Farooqi from the Institute of Metabolic Science at the University of Cambridge said: “There’s a reason why people lacking TRPC5 develop all of these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ – which enable humans and animals to survive – such as looking for food, social interaction, the flight or fight response, and caring for their infants. Our work shows that TRPC5 acts on oxytocin neurons in the hypothalamus to play a critical role in regulating our instincts.”

While deletions of the TRPC5 gene are rare, an analysis of DNA samples from around 500,000 individuals in UK Biobank revealed 369 people – around three-quarters of whom were women – that carried variants of the gene and had a higher-than-average body mass index.

The researchers say their findings suggests that restoring oxytocin could help treat people with missing or defective TRPC5 genes, and potentially mothers experiencing postnatal depression.

Professor Farooqi said: “While some genetic conditions such as TRPC5 deficiency are very rare, they teach us important lessons about how the body works. In this instance, we have made a breakthrough in understanding postnatal depression, a serious health problem about which very little is known despite many decades of research. And importantly, it may point to oxytocin as a possible treatment for some mothers with this condition.”

There is already evidence in animals that the oxytocin system is involved in both depression and in maternal care and there have been small trials into the use of oxytocin as a treatment. The team say their work provides direct proof of oxytocin’s role, which will be crucial in supporting bigger, multi-centre trials. 

Professor Farooqi added: “This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology, whether that’s our eating behaviour, anxiety or postnatal depression. We need to be more understanding and sympathetic towards people who suffer with these conditions.” 

This work was supported by Wellcome, the National Institute for Health and Care Research (NIHR), NIHR Cambridge Biomedical Research Centre, Botnar Fondation and Bernard Wolfe Health Neuroscience Endowment.

Source: University of Cambridge.

The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Categories : Metabolic DisordersTags :

Study Trials First Drug Therapy for Sleep Apnoea

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Photo by Ketut Subiyanto on Pexels

In an international phase III study, researchers have demonstrated the potential of tirzepatide, known to manage type 2 diabetes, as the first effective drug therapy for obstructive sleep apnoea (OSA), a sleep-related disorder characterised by repeated episodes of irregular breathing due to complete or partial blockage of the upper airway.

The results, published in the New England Journal of Medicine, highlight the treatment’s potential to improve the quality of life for millions around the world affected by OSA.

“This study marks a significant milestone in the treatment of OSA, offering a promising new therapeutic option that addresses both respiratory and metabolic complications,” said Atul Malhotra, MD, lead author of the study, professor of medicine at University of California San Diego School of Medicine and director of sleep medicine at UC San Diego Health.

OSA can result in reduced blood oxygen levels and can also be associated with an increased risk of cardiovascular complications, such as hypertension and heart disease. Recent studies, also led by Malhotra, suggest that the number of OSA patients worldwide is close to 936 million.

Conducted in two Phase III, double-blinded, randomised, controlled trials, the new study cohort recruited 469 participants from 9 countries with clinical obesity and living with moderate-to-severe OSA. Participants either used or did not use continuous positive airway pressure (CPAP) therapy, the most common sleep apnoea treatment which uses a machine to maintain an open airway during sleep, preventing interruptions in breathing. Patients were administered either 10 or 15mg of the drug by injection or a placebo and followed for 52 weeks.

Researchers found that tirzepatide led to a significant decrease in the number of breathing interruptions during sleep, a key indicator used to measure the severity of OSA. This improvement was much greater than what was seen in participants that were given a placebo. Importantly, some participants that took the drug reached a point where CPAP therapy might not be necessary. Considerable data suggest that a drug therapy that targets both sleep apnoea and obesity is beneficial rather than treating either condition alone.

Additionally, the drug therapy improved other aspects related to OSA, such as reducing the risk factors of cardiovascular diseases and improved body weight. The most common side effect reported was mild stomach issues.

“Historically, treating OSA meant using devices during sleep, like a CPAP machine, to alleviate breathing difficulties and symptoms,” Malhotra said. “However, its effectiveness relies on consistent use. This new drug treatment offers a more accessible alternative for individuals who cannot tolerate or adhere to existing therapies. We believe that the combination of CPAP therapy with weight loss will be optimal for improving cardiometabolic risk and symptoms. Tirzepatide can also target specific underlying mechanisms of sleep apnoea, potentially leading to more personalised and effective treatment.”

Malhotra adds that having a drug therapy for OSA represents a significant advancement in the field. 

“It means we can offer an innovative solution, signifying hope and a new standard of care to provide relief to countless individuals and their families who have struggled with the limitations of existing treatments,” said Malhotra. “This breakthrough opens the door to a new era of OSA management for people diagnosed with obesity, potentially transforming how we approach and treat this pervasive condition on a global scale.”

Next steps include conducting clinical trials to examine longer term effects of tirzepatide.

Source: Atrium Health Wake Forest Baptist

Categories : Metabolic DisordersTags :

Exercising during Pregnancy Normalises Eating Behaviours in Offspring from Obese Mice

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Source: Pixabay CC0

Maternal obesity impacts the eating behaviours of offspring via long-term overexpression of the microRNA miR-505-5p, according to a study publishing June 4 in the open-access journal PLOS Biology by Laura Dearden and Susan Ozanne from the MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, UK, and colleagues.

Previous studies in both humans and animal models have shown that the offspring of obese mothers have a higher risk of obesity and type 2 diabetes.

While this relationship is likely the result of a complex relationship between genetics and environment, emerging evidence has implicated that maternal obesity can disrupt the hypothalamus – the region of the brain responsible for nutrition sensing and energy homeostasis.

In animal models, offspring exposed to overnutrition during key periods of development eat more, but little is known about the molecular mechanisms that lead to these changes in eating behaviour.

In this study, researchers found that mice born from obese mothers had higher levels of the microRNA miR-505-5p in their hypothalamus – from as early as the foetal stage into adulthood.

The researchers found that the mice ate more and showed a preference for high-fat foods.

Interestingly, the effect of maternal obesity on miR-505-5p and eating behaviours was mitigated if the mothers exercised during pregnancy.

Cell culture experiments showed that miR-505-5p expression could be induced by exposing hypothalamic neurons to long-chain fatty acids and insulin, which are both high in pregnancies complicated by obesity.

The researchers identified miR-505-5p as a novel regulator of pathways involved in fatty acid uptake and metabolism, therefore high levels of the miRNA make the offspring brain unable to sense when eating high fat foods.

Several of the genes that miR-505-5p regulates have been associated with high body mass index in human genetic studies.

The study is one of the first to demonstrate the molecular mechanism linking nutritional exposure in utero to eating behaviour.

The authors add, “Our results show that obesity during pregnancy causes changes to the baby’s brain that makes them eat more high fat food in adulthood and more likely to develop obesity. Importantly we showed that moderate exercise, without weight loss, during pregnancies complicated by obesity prevented the changes to the baby’s brain. This helps us understand why the children of mothers living with obesity are more likely to become obese themselves, with early life exposures, genetics and current environment all being contributing factors.”

Provided by PLOS