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Mutated gene helps regulate appetite, weight and insulin, study suggests

A mutated gene plays a key role in regulating bodyweight, a study has suggested, helping to control parts of the brain responsible for appetite, metabolism and growth.

    Cake in fridge
    The mutated gene helps control parts of the brain responsible for appetite, metabolism and growth

    Scientists at Nottingham Trent University and MRC Harwell found that the gene, previously associated with a lower BMI in people, could switch on and off the function of other genes in the hypothalamus region of the brain which influence energy balance and body growth.

    It is the first time researchers have been able to understand the role and mechanism of the ‘ZFHX3’ gene in this process.

    They argue that understanding the specific pathway in the brain through which this occurs  could help pave the way for new targeted weight loss therapies.  

    Obesity is a global pandemic and a major contributor to preventable death worldwide and is responsible for type 2 diabetes, cardiovascular disease and some cancers.

    In their study, the Nottingham team found that mice with the mutated gene had a lower food intake, weighed less, had a shorter body length, lower fat mass and lower insulin and leptin hormone levels.

    Over the course of the study mice with the mutated gene ate about 12% less than mice with a non-mutated gene and at one year old weighed about 20% less.

    The lower hormone levels, which are seen in both people and mice with less body fat suggests that they have healthier blood sugar regulation and therefore less likely to be at risk from metabolic disease such as type 2 diabetes and cardiovascular disease.

    The work involved looking at which parts of the brain were showing changes in gene expression and revealed that they were all involved in the regulation of weight.

    While everyone has the gene, the specific mutation thought to be driving this mechanism – which is naturally occurring – is thought to exist in just four percent of people.

    “The hypothalamus is a brain region classically associated with regulation of appetite and energy expenditure,” said Dr Rebecca Dumbell, a researcher in Nottingham Trent University’s School of Science and Technology.

    She said: “For the first time, we have demonstrated a role for this gene to alter growth and energy balance with a protein altering mutation similar to a variant found at low frequency in the human population.

    “There is a big genetic component related to our appetite and growth but it’s not fully understood. Understanding what is happening in those who have the mutation paves the way to exploring potential new weight loss intervention targets for all people.

    “This mutation drives lower food intake, fat mass and metabolic hormones and this could all help provide protection from metabolic disease.”

    Dr Rebecca Dumbell has just received £100,000 funding from the Academy of Medical Sciences as part of a two year project to further explore the role of the gene on food intake, growth and metabolism.

    The latest study, which also involved the University of Aberdeen, is published in the FASEB (Federation of American Societies for Experimental Biology) journal.

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      Nottingham Trent University (NTU) received the Queen’s Anniversary Prize for Higher and Further Education in 2021 for cultural heritage science research. It is the second time that NTU has been bestowed the honour of receiving a Queen’s Anniversary Prize for its research, the first being in 2015 for leading-edge research on the safety and security of global citizens.

      The Research Excellence Framework (2021) classed 83% of NTU’s research activity as either world-leading or internationally excellent. 86% of NTU’s research impact was assessed to be either world-leading or internationally excellent.

      NTU was awarded The Times and The Sunday Times Modern University of the Year 2023 and ranked University of the Year in the Whatuni Student Choice Awards 2023. It was awarded Outstanding Support for Students 2020 (Times Higher Education Awards), University of the Year 2019 (Guardian University Awards, UK Social Mobility Awards), Modern University of the Year 2018 (Times and Sunday Times Good University Guide) and University of the Year 2017 (Times Higher Education Awards).

      NTU is the 5th largest UK institution by student numbers, with approximately 40,000 students and more than 4,400 staff located across five campuses. It has an international student population of 7,000 and an NTU community representing over 160 countries.

      Since 2000, NTU has invested £570 million in tools, technology, buildings and facilities.

      NTU is in the UK’s top 10 for number of applications and ranked first for accepted offers (2021 UCAS UG acceptance data). It is also among the UK’s top five recruiters of students from disadvantaged backgrounds and was the first UK university to sign the Social Mobility Pledge.

      NTU is ranked the second most sustainable university in the world in the 2022 UI Green Metric University World Rankings (out of more than 900 participating universities).

    Published on 27 November 2023
    • Subject area: Sciences including sport sciences
    • Category: Press office; Research; School of Science and Technology