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The researchers say their findings add further evidence to the relevance of brain structure to weight and food consumption.

Current estimations suggest that over 1.9 billion people worldwide are either overweight or obese. In the UK, according to the Office for Health Improvement & Disparities, almost two-thirds of adults are overweight or living with obesity. This increases an individual’s risk of developing a number of health problems, including type 2 diabetes, heart disease and stroke, cancer and poorer mental health.

A large number of factors influence how much we eat and the types of food we eat, including our genetics, hormone regulation, and the environment in which we live. What happens in our brains to tell us that we are hungry or full is not entirely clear, though studies have shown that the hypothalamus, a small region of the brain about the size of an almond, plays an important role.

Dr Stephanie Brown from the Department of Psychiatry and Lucy Cavendish College, University of Cambridge, said: “Although we know the hypothalamus is important for determining how much we eat, we actually have very little direct information about this brain region in living humans. That’s because it is very small and hard to make out on traditional MRI brain scans.”

The majority of evidence for the role of the hypothalamus in appetite regulation comes from animal studies. These show that there are complex interacting pathways within the hypothalamus, with different cell populations acting together to tell us when we are hungry or full.

To get around this, Dr Brown and colleagues used an algorithm developed using machine learning to analyse MRI brain scans taken from 1,351 young adults across a range of BMI scores, looking for differences in the hypothalamus when comparing individuals who are underweight, healthy weight, overweight and living with obesity.

In a study published today in Neuroimage: Clinical, the team found that the overall volume of the hypothalamus was significantly larger in the overweight and obese groups of young adults. In fact, the team found a significant relationship between volume of the hypothalamus and body-mass index (BMI).

These volume differences were most apparent in those sub-regions of the hypothalamus that control appetite through the release of hormones to balance hunger and fullness.

While the precise significance of the finding is unclear – including whether the structural changes are a cause or a consequence of the changes in body weight – one possibility is that the change relates to inflammation. Previous animal studies have shown that a high fat diet can cause inflammation of the hypothalamus, which in turn prompts insulin resistance and obesity. In mice, just three days of a fat-rich diet is enough to cause this inflammation. Other studies have shown that this inflammation can raise the threshold at which animals are full – in other words, they have to eat more food than usual to feel full.

Dr Brown, the study’s first author, added: “If what we see in mice is the case in people, then eating a high-fat diet could trigger inflammation of our appetite control centre. Over time, this would change our ability to tell when we’ve eaten enough and to how our body processes blood sugar, leading us to put on weight.”

Inflammation may explain why the hypothalamus is larger in these individuals, the team say. One suggestion is that the body reacts to inflammation by increasing the size of the brain’s specialist immune cells, known as glia.

Professor Paul Fletcher, the study’s senior author, from the Department of Psychiatry and Clare College, Cambridge, said: “The last two decades have given us important insights about appetite control and how it may be altered in obesity. Metabolic researchers at Cambridge have played a leading role in this.

“Our hope is that by taking this new approach to analysing brain scans in large datasets, we can further extend this work into humans, ultimately relating these subtle structural brain findings to changes in appetite and eating and generating a more comprehensive understanding of obesity.”

The team say more research is needed to confirm whether increased volume in the hypothalamus is a result of being overweight or whether people with larger hypothalami are predisposed to eat more in the first place. It is also possible that these two factors interact with each other causing a feedback loop.

The research was supported by the Bernard Wolfe Health Neuroscience Fund, Wellcome and the NIHR Cambridge Biomedical Research Centre, with additional funding from Alzheimer’s Research UK.

Reference
Brown, SSG, et al. Hypothalamic volume is associated with body mass index. Neuroimage: Clinical; 8 Aug 2023; DOI: 10.1016/j.nicl.2023.103478

Cambridge scientists have shown that the hypothalamus, a key region of the brain involved in controlling appetite, is different in the brains of people who are overweight and people with obesity when compared to people who are a healthy weight.

Although we know the hypothalamus is important for determining how much we eat, we actually have very little direct information about this brain region in living humansStephanie BrownWorld Obesity FederationMan playing basketball

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The team is exploring the capacity robots have to inspire self-reflection, and support the work of psychologists and clinicians. 

The unborn baby ‘remote controls’ its mother’s metabolism so the two are in a nutritional tug of war. The mother’s body wants the baby to survive but needs to keep enough glucose and fats circulating in her system for her own health, to be able to deliver the baby, breastfeed and to reproduce again.

A new study from the University of Cambridge published today examines how the placenta communicates with the mother through the release of hormones so she will accommodate her baby’s growth. The placenta is a vital organ that develops with the fetus in pregnant women and other female mammals to support the developing fetus. In pregnant mice, scientists selectively altered the signalling cells in the placenta that tell mothers to allocate nutrients to her developing fetuses.

Professor Amanda Sferruzzi-Perri, Professor in Fetal and Placental Physiology, a Fellow of St John’s College and co-senior author of the paper, said: “It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetus.”

Dr Miguel Constancia, MRC Investigator based at the Wellcome-MRC Institute of Metabolic Science and co-senior author of the paper, said: “The baby’s remote control system is operated by genes that can be switched on or off depending on whether they are a ‘dad’s’ or ‘mum’s’ gene’, the so-called imprinted genes.

“Genes controlled by the father are ‘greedy’ and ‘selfish’ and will tend to manipulate maternal resources for the benefit of the fetuses, so to grow them big and fittest. Although pregnancy is largely cooperative, there is a big arena for potential conflict between the mother and the baby, with imprinted genes and the placenta thought to play key roles.”

The findings by researchers from the Centre for Trophoblast Research at Cambridge’s Department of Physiology, Development and Neuroscience and the Medical Research Council Metabolic Diseases Unit, part of the Wellcome-MRC Institute of Metabolic Science, have been published in Cell Metabolism.

The baby’s genes controlled by the father tend to promote fetal growth and those controlled by the mother tend to limit fetal growth.

Professor Sferruzzi-Perri explained: “Those genes from the mother that limit fetal growth are thought to be a mother’s way of ensuring her survival, so she doesn’t have a baby that takes all the nutrients and is too big and challenging to birth. The mother also has a chance of having subsequent pregnancies potentially with different males in the future to pass on her genes more widely.”

Researchers deleted the expression of an important imprinted gene called Igf2, which provides instructions for making a protein called ‘Insulin Like Growth Factor 2’. Similar to the hormone insulin, which is responsible for making and controlling glucose levels in our circulation, the gene promotes fetal growth and plays a key part in the development of fetal tissues including the placenta, liver and brain.

Dr Jorge Lopez-Tello, a lead author of the study based at the University’s Department of Physiology, Development and Neuroscience, said: “If the function of Igf2 from the father is switched off in signalling cells, the mother doesn’t make enough amounts of glucose and lipids – fats – available in her circulation. These nutrients therefore reach the fetus in insufficient amounts and the fetus doesn’t grow properly.”

The scientists found that deleting Igf2 from the placenta’s signalling cells affects the production of other hormones that modulate the way the mother’s pancreas produces insulin, and how her liver and other metabolic organs respond.

“We found Igf2 controls the hormones responsible for reducing insulin sensitivity in the mother during pregnancy. It means the mother’s tissues don’t absorb glucose so nutrients are more available in the circulation to be transferred to the fetus,” said Professor Sferruzzi-Perri.

Babies with Igf2 gene defects can be overgrown or growth-stunted. “Until now, we didn’t know that part of the Igf2 gene’s role is to regulate signalling to the mother to allocate nutrients to the fetus,” added Professor Sferruzzi-Perri.

The mice studied were smaller at birth and their offspring showed early signs of diabetes and obesity in later life.

Professor Sferruzzi-Perri said: “Our research highlights how important the controlled allocation of nutrients to the fetus is for the lifelong health of the offspring, and the direct role the placenta plays.

“The placenta is an amazing organ. At the end of pregnancy, the placenta is delivered by the mother, but the memories of how the placenta was functioning leaves a lasting legacy on the way those fetal organs have developed and then how they’re going to function through life.”

The next step is to understand how placental hormones are controlled by Igf2 and what those hormones are doing. Future research could help scientists discover new strategies to target the placenta to improve health outcomes for mums and babies.

Mice are used in research because the organisation of their DNA and their gene expression is similar to humans, with ninety-eight percent of human genes having a comparable gene in the mouse. They have similar reproductive and nervous systems to humans, and suffer from many of the same diseases such as obesity, cancer and diabetes.

Reference
Lopez-Tello, J et al. Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene. Cell Metabolism; 11 July 2023; DOI: 10.1016/j.cmet.2023.06.007

Adapted from a press release from St John’s College Cambridge

A study in mice has found that fetuses use a copy of a gene inherited from their dad to force their mum to release as much nutrition as possible during pregnancy.

It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetusAmanda Sferruzzi-PerriUnderstanding Animal ResearchBrown mouse

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Encouraging adolescents to feel capable and purposeful – rather than just happy – could improve their academic results as well as their mental health, according to new research which recommends changing how wellbeing is supported in schools.

The University of Cambridge study, involving over 600 teenagers from seven English schools, examined two separate aspects of their wellbeing: life satisfaction and ‘eudaimonia’. While life satisfaction roughly equates to how happy a person is, eudaimonia refers to how well that person feels they are functioning. It incorporates feelings of competence, motivation and self-esteem.

Researchers found that students with high levels of eudaimonia consistently outperformed their peers in GCSE-level assessments, especially Maths. On average, those achieving top Maths grades had eudaimonic wellbeing levels 1.5 times higher than those with the lowest grades.

No such link was found between academic performance and life satisfaction. Despite this, child wellbeing policy in England tends to focus on life satisfaction. The Government has, for example, recently added ‘happiness’ to national curricula as part of its Relationships, Sex and Health Education (RSHE) guidance, emphasising teaching adolescents how to feel happy and resilient while managing negative emotions.

Previous research has pointed to the importance of fostering adolescents’ eudaimonic wellbeing by nurturing their personal values, goals and sense of self-worth. The new study appears to strengthen that case by demonstrating a positive link between eudaimonia and academic performance.

Its lead author, Dr Tania Clarke, is a psychologist of education who now works for the Youth Endowment Fund, but undertook the study for her doctoral research at the Faculty of Education, University of Cambridge. The findings are published in School Psychology Review.

“Wellbeing education often focuses on teaching students about being happy and not being sad.” Clarke said. “That is over-simplistic and overlooks other vital qualities of wellbeing that are particularly salient during the formative period of adolescence.”

“Adolescents also need to develop self-awareness, confidence, and ideally a sense of meaning and purpose. Judging by our findings, an adolescent who is currently getting a 3 or 4 on their Maths GCSE could be helped to rise a couple of grades if schools emphasised these qualities for all students, rather than just promoting positivity and minimising negative emotions.”

The study involved 607 adolescents, aged 14-15. Participants completed an established psychological assessment called ‘How I feel about myself and school’, which measures both life satisfaction and eudaimonia, as well as feelings of interpersonal relatedness and negativity.

These measures were compared with their scores in mock English and Maths GCSEs. The research also assessed whether the students exhibited a ‘growth mindset’: a belief in their personal capacity for improvement. Many educators consider this essential for enhancing academic performance.

The students’ overall wellbeing – their eudaimonia and life satisfaction combined – clearly correlated positively with their exam results. Those attaining top Maths grades (Grades 8 or 9) had, on average, a wellbeing score of 32 out of a possible 50. This was nine points higher than those with a Grade 1, and three to four points higher than the average for all 607 students.

When they analysed the separate dimensions of wellbeing, however, the researchers found a positive relationship between eudaimonia and higher attainment, but no correlation with life satisfaction. In Maths, the average eudaimonic wellbeing score of Grade 9 students was 17.3 from a possible 25, while that of Grade 1 students was just 10.9. These results held true even when accounting for potentially confounding factors, such as school attended, gender, socio-economic status, or special educational needs.

The study also found that a growth mindset did not predict good academic results, although students with high eudaimonic wellbeing did tend to exhibit such a mindset. Other research has similarly struggled to draw a clear link between growth mindset and academic progress, but does link it more generally to positive mental health. This implies that eudaimonia, as well as supporting better attainment, may also underpin important aspects of self-belief, leading to broader mental health benefits.

Clarke’s wider research suggests that various constraints currently limit schools’ capacity to promote eudaimonic wellbeing. In an earlier Review of Education article she published the results of in-depth interviews with some of the same students, which highlighted concerns about a ‘performativity culture’ stemming from a heavy emphasis on high-stakes testing. These interviews indicated that many students associate ‘doing well’ with getting good grades, rather than with their own strengths, values and goals.

Students said they often felt worthless, inadequate or “dumb” if they failed to get high marks in tests. “You let your scores define you,” one student told Clarke. “Then you feel really low about… your worth and everything. You think it’s literally the end of the world.” Ironically, the new findings suggest that by limiting teachers’ capacity to support students’ personal growth, the heavy emphasis on exam results and testing may be undermining academic progress, at least in some cases.

Clarke suggested that eudaimonic therapy, which increasingly features in professional mental health psychology for adolescents, could be incorporated more into wellbeing education. In particular, her study underscores the need to help students understand their academic work and progress in the context of their personal motivations and goals.

“There is a link between better wellbeing and a more nuanced understanding of academic success,” Clarke said. “Because schools are under heavy pressure to deliver academic results, at the moment students seem to be measuring themselves against the exam system, rather than in terms of who they want to be or what they want to achieve.”

Dr Ros McLellan, from the Faculty of Education, University of Cambridge, who co-authored the study, said: “Wellbeing education needs to move beyond notions of ‘boosting’ happiness towards deeper engagement, helping adolescents to realise their unique talents and aspirations, and a sense of what happiness means for them, personally. This would not just improve wellbeing: it is also likely to mean better exam results, and perhaps fewer issues for students later on.”

Study of 600 teenagers suggests that having stronger self-awareness and sense of purpose may raise GCSE Maths scores “by a couple of grades”.

Wellbeing education needs to move beyond notions of ‘boosting’ happiness towards deeper engagement, helping adolescents to realise their unique talents and aspirationsRos McLellanStudents in the classroom

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These ‘Green’ farming policies risk worsening the global biodiversity crisis by reducing how much food is produced in a region, driving up food imports and increasing environmental damage overseas.

In an article published today in the journal Nature, Professor Andrew Balmford at the University of Cambridge, and Professor Ian Bateman at the University of Exeter, urge policy-makers to consider a bolder approach known as ‘land sparing’ - which they argue is cheaper, more effective, and avoids displacing food production and worsening the loss of wildlife habitats overseas.

Land sparing involves finding lower-impact ways to boost yields in farmed areas, and allow larger, non-farmed areas of the landscape to be put aside for nature - without increasing imports and damaging overseas wildlife.

The researchers say the approach has been overlooked by policymakers because of a failure to consider the wider consequences of changes in land management. They argue that changes that boost wildlife locally seem superficially attractive, but if food production is reduced there are unavoidable knock-on effects elsewhere that must also be taken into account.

They also cite the influence of the ‘Big Farm’ lobby in maintaining the status quo in agricultural policy, with land-sharing subsidies allocated using a flat rate per hectare, which disproportionately benefits the biggest farms – resulting in the largest 12 per cent of farms taking 50 per cent of all UK taxpayer subsidies.

Their article debunks some of the benefits to biodiversity of three widely-advocated green farming approaches.

They argue that while policy funded measures such as reducing the use of pesticides and fertilisers can sometimes increase populations of more common animals and plants on farms it does little for endangered birds, invertebrates, plants and fungi species that need larger stretches of non-farmed habitat – and by lowering yields can also make matters far worse for overseas biodiversity.

Rewilding initiatives, where large areas of land are taken out of farming, can indeed benefit locally endangered species. But unless other areas see compensating increases in food output then this reduces local production, increases demand for food imports, and so damages biodiversity overseas.

They also argue that organic farming, where crops are produced without manufactured fertilisers and modern pesticides, is even more likely to be damaging. Relatively few species will benefit in the farmed area, and the substantially lower yields from this type of farming risk greatly increasing the need for food imports, and hence a country’s impacts on biodiversity elsewhere.

Land sparing, in contrast, involves retaining or creating sizeable blocks of unfarmed land containing larger populations of the many species that depend on natural habitats, as well as boosting farm yields elsewhere in the region so that overall production is maintained or even increased.

Promising methods to boost crop and livestock yields more sustainably than current high-yield practices include genomic screening and gene editing to accelerate animal and crop breeding; using new advances in aquaculture to produce high value foods with much lower environmental impacts; and, in tropical countries, greater access to improved pasture and veterinary care.  

The researchers point to field studies on five continents that consistently show how land sparing delivers far greater biodiversity gains than conventional ‘nature friendly farming’ policies.

They say it is likely to cost a great deal less as well: a survey of UK farmers last year found that land sparing could deliver the same biodiversity outcomes for birds as conventional approaches but at 48 per cent of the cost to taxpayers, and with a 21 per cent lower impact on food production.

Professor Bateman, a Professor of Environmental Economics at the University of Exeter Business School who has advised seven UK secretaries of state for the environment in the past decade, said:

“The stakes are too high for policymakers to continue to ignore the promise of land sparing when so much research demonstrates that it is a far more effective approach than many of the strategies being deployed.

“Unless researchers and policymakers assess the overall, global effects of interventions aimed at addressing biodiversity loss and climate change, poor decisions that are unsupported by the data will at best under-deliver, and at worst exacerbate existential threats posed by the extinction and climate crises.”

Andrew Balmford, a Professor of Conservation Science at the University of Cambridge who has led 20 years’ work investigating how to reconcile food production with biodiversity conservation, added:

“This issue has become even more urgent since last December when many countries agreed to help meet the Convention on Biological Diversity’s goal of protecting 30 per cent of the planet’s land and oceans by 2030.

“Exactly how this 30 per cent will be put aside - and how we meet humanity’s growing needs on the rest of planet - will in large part determine the biodiversity consequences of this ambitious commitment.”

Reference

Bateman, I. and Balmford, A.: ‘Current conservation policies risk accelerating biodiversity loss.’ Nature, June 2023.

Adapted from a press release by the University of Exeter.

Rewilding, organic farming and the so-called ‘nature friendly farming’ measures included in some government conservation policies may accelerate global biodiversity loss, say two leading researchers.

Joyce G on Unsplash

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