Translation of the original article
The University of Hong Kong
Journal reference: Chen, K., et al. (2022) Adipose-targeted triiodothyronine therapy counteracts obesity-related metabolic complications and atherosclerosis with negligible side effects. doi.org/10.1038/s41467-022-35470-4.
Obesity is a major risk factor for many life-threatening chronic diseases, such as diabetes, cardiovascular diseases, and neurodegenerative disorders.
Thyroid hormone is an ancient hormone with therapeutic potential in obesity and related medical complications by stimulating energy expenditure. However, despite extensive research efforts in recent decades, clinical trials have failed to demonstrate clear clinical benefits of chronic systemic administration of thyroid hormone in weight reduction in obese individuals. Additionally, due to the widespread expression of thyroid hormone receptors, systemic administration of thyroid hormones often leads to serious adverse effects on many organs, such as tachycardia, heart attack, muscle atrophy, and osteoporosis.
Skeletal muscles and adipose tissue are considered the two main target organs where thyroid hormones exert a stimulating effect on metabolic rate and energy expenditure.
The research team developed encapsulated thyroid hormones—peptide-modified nanoparticles for selective delivery of thyroid hormones to adipose tissues. Notably, researchers found that TG delivery targeted at adipose tissue is significantly more effective than systemic TG therapy in reducing obesity and related metabolic complications, without adverse effects on other, non-adipose tissues.
Mechanically, the study showed that TG therapy targeting adipose tissue can convert “bad” white fat into “good” brown fat, which can burn calories by releasing heat, while systemic TG therapy cannot cause the “browning” of white fat due to its suppression of sympathetic nerves. Additionally, the research team made an unexpected finding that TG delivery targeted at adipose tissue effectively alleviates hypercholesterolemia and atherosclerosis.
This is the first study of safe pharmacotherapy for obesity and its related cardiometabolic complications, demonstrating high effectiveness.
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