August 2015 | Issue 19
Inaugural NHG-NTU Clinician-Scientist tackles a weighty problem

 

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By Nicole Lim
Assistant Director, Communications & External Relations​​​​​

Eat your way into a smaller waist size? Impossible? Not necessarily, according to Associate Professor Melvin Leow.​​

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Associate Professor Melvin Leow

The senior consultant endocrinologist at Tan Tock Seng Hospital and inaugural recipient of the NHG-NTU Clinician-Scientist Fellowship is working on several projects to elucidate the key mechanisms that help regulate body weight based on the effect of thyroid hormone on metabolic rate via brown fat activation. Brown fat or brown adipose tissue is a healthy type of fat that acts as a fat-burning furnace.


Key to ‘knife-less bariatric 
surgery’?
Brown fat was thought to only be present only in newborns for non-shivering thermoregulation. But recently, it has been found in varying amounts in adults. Thyroid hormone as well as certain foods can stimulate it to generate heat by burning stored calories. Assoc Prof Leow said, “If we can find ways to safely expand the proportion of brown fat in the body and stimulate its catabolic activity, then we could theoretically reach a point in the future where it might mimic the efficacy of bariatric surgery. That will be the holy grail.”

But for that to be possible, more accessible and less expensive imaging techniques than the current gold standard ionising radiation riddled PET are needed to monitor brown fat amounts and activity. Exploring other imaging modalities, Assoc Prof Leow and his team have shown that infrared imaging can reliably capture the heat signatures of brown fat. Certain foods such as chilli and pepper, which contain capsaicin, are known to increase metabolic rate. Assoc Prof Leow and his team demonstrated brown fat activation by capsinoids using infrared thermal imaging which convinced him that this method can replace PET and accelerate brown fat research.

To explore this technology further, he received the prestigious National Medical Research Council Clinician Scientist Award earlier this year. “We’re now going to validate this tool first in healthy volunteers and then in thyroid patients to see whether it could become the new gold standard,” said Assoc Prof Leow, who is also the Clinical Deputy Director of the Clinical Nutrition Research Centre based at the Centre for Translational Medicine at NUS campus.

Working with image processing scientists from A*STAR’s Institute for Infocomm Research, Assoc Prof Leow’s research team also developed a novel way to quantify thermograms into infrared radiative power readouts in watts. “Eventually, we want to come-up with an app that can compute brown fat activity from a thermogram selfie that you take with your smartphone after eating. I believe that this can act as ‘biofeedback’ to motivate people to modify their eating behaviour, a necessary component for lasting change as far as durability of a successful weight loss and maintenance strategy goes,” he said.

 
Fine-tuning thyroid hormonal balance
Assoc Prof Leow’s other related research interest focuses on thyroidology. Treating patients with thyroid hormone imbalances, he noticed that even after returning thyroid levels to normal with treatment, some patients continued to feel unwell, and have suboptimal energy levels or weight control.

A keen mathematics enthusiast, Assoc Prof Leow single-handedly derived a mathematical formula expressing the fundamental natural law governing the thyroid hormone system, which he published in the Journal of Theoretical Biology in 2007. With help from an unexpected source, Assoc Prof Leow’s general solution was tweaked to yield special solutions predicting an individual’s unique hormonal set-point, dictating the right amount of thyroid hormone essential for optimal metabolic health. “I got a call out of the blue from an electronics engineer-cummathematician from the Netherlands who stumbled upon my mathematical model and said that equation could be modified for personalised clinical application,” said Assoc Prof Leow. By introducing two parameters and after some calculus-style brainstorming, the two scientists came up with personalisable formulae named the Leow-Goede Equations of Euthyroidism, which was published in Theoretical Biology and Medical Modelling in 2014.

Armed with much determination and perseverance, he and his colleagues managed to patent this algorithm. Aided by a grant from A*STAR’s Exploit Technologies, the algorithm was turned into a ‘Set-Point Optimisation and Targeting’ software programme, Thyroid-SPOT for short, last year. Now, during his Clinician-Scientist Fellowship, Assoc Prof Leow plans to embark on a multi-centre double-blind prospective randomised clinical trial to test the software. “If the results of the study are really positive, then we may consider applying for FDA approval and licensing.”

While Assoc Prof Leow’s research may lead to easier ways to manage one’s weight, he was quick to point out that exercise shouldn’t be forgotten. “The cornerstones of effective long-term weight management will always be diet and exercise, but knowing that certain food choices can activate brown fat and favourably impact on metabolism may help people with their long-term weight goals. This line of research may also open possibilities of developing thyromimetic molecules that specifically target brown adipose tissue pathways without the undesirable side effects of thyroid hormones to combat obesity one day.”