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Obesity has been a long-standing problem for the UK, only intensified by the curtailing of government fitness programmes amidst the pandemic. It is estimated that in 2019 there were over 11,000 hospital admissions directly attributable to obesity, an increase of 4% compared to 2018. Successive governments have attempted to curb the epidemic through measures such as Boris bikes and 5-a-day campaigns however UK child obesity rates have refused to budge, showing no significant improvement for the last 15 years and remaining one of the highest in Europe. With the majority of the UK’s adults being identified as overweight or obese, it is clear that a new approach is needed. As it happens, one of our very own King’s professors, Dr Helen Cox, has been working on an exciting (but still in development) new treatment concept for obesity patients which would rely on the body’s own signalling pathways to induce weight loss. Here we explore the science at the cutting edge of anti-obesity treatments and how Dr Cox’s research aims to trick our body into producing its own anti-obesity hormones.
Sparsely populating our gastrointestinal tract lie specialised signalling cells known as “L-cells” which act as the gut’s communication hub, passing along chemical messages in the form of hormones that initiate weight loss (or weight gain) in a patient. Among the most crucial of the weight loss hormones are PYY and GLP1, which increase gut motility and generate feelings of satiety. Anomalies in PYY and GLP1 signalling are attributed to well-known metabolic disorders such as type-2 diabetes and represent a significant contribution to the UK’s obesity crisis. Dr Cox, professor of pharmacology at King’s College London, has been looking at ways to take advantage of these hormones in designing new types of anti-obesity therapies, which would trick L-cells into secreting PYY and GLP1 causing controlled, natural weight loss. Using the body’s endogenous hormones to treat metabolic disorders is thought to be, not only more effective, but safer for the patient, producing longer lasting results at a lower risk. Using a rodent model and a piece of hardware known as an Ussing chamber, Dr Cox tests the effectiveness of different drugs in stimulating L-cells in the rat colon. A successful stimulation of the L-cells will lead to a reduction in the presence of chloride ions, which she uses as a measure of the drug’s potency. Dr Cox aims to further develop these treatments by finding the most efficient way to amplify PYY and GLP1 release. Her paper was the first to highlight the importance of PYY in gut signalling and paved the way for future research into L-cell activating drugs. Dr Cox found that these important peptide hormones were being secreted continuously, in an almost constant fashion, something which was previously unknown to the research community. According to her, this experiment serves as a testament to “how little we know about the gut and how we can use pharmacological tools to find out more”.
Following a 2018 survey by the NHS, 65% of UK adults were placed in a higher risk bracket for heart attack and stroke on account of their weight, constituting a sizable financial burden for our already struggling health services. Interestingly, L-cell dysfunction, correlated with high fat diets, is thought to lead to many of the symptoms associated with obesity including weight gain and metabolic dysregulation. Current anti-obesity treatment such as mitochondrial uncouplers can lead to severe side effects and invasive procedures such as bariatric surgery are only available to the NHS’s most extreme cases. L-cell activator research still has a ways to go before developing into a human treatment, but it is hoped that the groundwork laid by Dr Cox and her team will help pharmacologists develop safer, more effective therapies for obesity patients in the coming years.
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