One function of thyroid hormones is to control energy availability and expenditure. Some individuals have mutations in their thyroid hormone receptor-beta (THRB) gene and are resistant to the effects of thyroid hormones. This causes their levels of circulating thyroid hormones to become elevated, but the effects of this have not been completely determined.
However, a team of researchers, led by Kitt Falk Petersen and Krishna Chatterjee, at Yale University School of Medicine, New Haven, and Cambridge University, United Kingdom, has now determined that adults and children with THRB mutations have markedly increased resting energy expenditure.
Further analysis identified a process known as mitochondrial uncoupling in skeletal muscle, due to tissue selective retention of thyroid hormone receptor-alpha sensitivity to elevated thyroid hormone levels, as a predominant mechanism contributing to this effect.
The authors therefore suggest that further studies of individuals resistant to the effects of thyroid hormones will help clarify the relative contribution of different forms of thyroid hormone receptor in different target tissues.
The research appears in the Journal of Clinical Investigation.
- Catherine S. Mitchell, David B. Savage, Sylvie Dufour, Nadia Schoenmakers, Peter Murgatroyd, Douglas Befroy, David Halsall, Samantha Northcott, Philippa Raymond-Barker, Suzanne Curran, Elana Henning, Julia Keogh, Penny Owen, John Lazarus, Douglas L. Rothman, I. Sadaf Farooqi, Gerald I. Shulman, Krishna Chatterjee and Kitt Falk Petersen. Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI38793
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