Thyroid hormones may hold key to treating metabolic diseases

Asst Prof Rohit Sinha (left) with Prof Paul Yen
Asst Prof Rohit Sinha (left) with Prof Paul Yen

A study, led by Assistant Professor Rohit Sinha and Professor Paul Yen from Duke-NUS, has uncovered a novel cellular system regulated by thyroid hormones. The discovery may help develop new approaches in the treatment of metabolic diseases. Metabolic and age-related diseases such as diabetes, cardiovascular disorders and non-alcoholic fatty liver disease are on the rise worldwide, particularly in ageing populations like Singapore.

Serving as the cell’s battery pack, the function and activity of mitochondria must be kept in check to keep the cell running. When this ‘battery’ is impaired, a ‘garbage removal’ mechanism known as mitophagy replaces the old mitochondrion with a new and working one. Thyroid hormones play a role in the replacement process though it was previously unclear whether they also coordinate the removal.

In studies conducted on mouse and human liver cells, Dr Yen and his team from the Duke-NUS Programme in Cardiovascular and Metabolic Disorders, confirmed that thyroid hormones are important coordinators in the removal and replacement process of mitochondria.

Thyroid hormones start the removal process by activating a known mitophagy protein – ULK1. The team tracked the activated ULK1 and found that it travels to damaged or old mitochondria, priming them for removal. This insight will give researchers a target for future drug development to reverse the effects of ageing and other damage to cell activity by speeding up the removal – and thus replacement – of worn-out mitochondria. This would help return the cell to its proper working order, quicker.

“Without this removal process, new mitochondria cannot replace the old and the cell would wear out,” explained senior author Dr Yen, Director of the Laboratory of Hormonal Regulation at Duke-NUS. “Our findings collectively show that thyroid hormones, with roles in both processes, are important for maintaining the quality of mitochondria in the liver and presumably other tissues in the body. Since impaired mitochondria quality control features heavily in metabolic and age-related diseases, application of thyroid hormones may be beneficial in these areas,” added first author Dr Sinha.

Currently, Dr Yen and his team, with funding from the Tanoto Foundation, are examining the effects of low-dose thyroid hormone treatments on diabetic patients in Singapore. This is in partnership with the Singapore Institute of Clinical Research and the Metabolic Research Network.

This study was published in Autophagy, and is supported by the A*STAR Translational Clinical Research Partnership Award, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award, and the Singapore National Research Foundation under its Clinician Scientist Individual Research Grant and under its CBRG New Investigator Grant administered by the Singapore Ministry of Health’s National Medical Research Council.