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Publication
The paradoxical lean phenotype of hypothyroid mice is marked by increased
adaptive thermogenesis in the skeletal muscle.
Authors Kaspari RR, Reyna-Neyra A, Jung L, Torres-Manzo AP, Hirabara SM, Carrasco N
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2020
Date Published 9/1/2020
Volume : Pages 117 : 22544 - 22551
PubMed Reference 32826330
Abstract Obesity is a major health problem worldwide, given its growing incidence and its
association with a variety of comorbidities. Weight gain results from an
increase in energy intake without a concomitant increase in energy expenditure.
To combat the obesity epidemic, many studies have focused on the pathways
underlying satiety and hunger signaling, while other studies have concentrated
on the mechanisms involved in energy expenditure, most notably adaptive
thermogenesis. Hypothyroidism in humans is typically associated with a decreased
basal metabolic rate, lower energy expenditure, and weight gain. However,
hypothyroid mouse models have been reported to have a leaner phenotype than
euthyroid controls. To elucidate the mechanism underlying this phenomenon, we
used a drug-free mouse model of hypothyroidism: mice lacking the sodium/iodide
symporter (NIS), the plasma membrane protein that mediates active iodide uptake
in the thyroid. In addition to being leaner than euthyroid mice, owing in part
to reduced food intake, these hypothyroid mice show signs of compensatory
up-regulation of the skeletal-muscle adaptive thermogenic marker sarcolipin,
with an associated increase in fatty acid oxidation (FAO). Neither
catecholamines nor thyroid-stimulating hormone (TSH) are responsible for
sarcolipin expression or FAO stimulation; rather, thyroid hormones are likely to
negatively regulate both processes in skeletal muscle. Our findings indicate
that hypothyroidism in mice results in a variety of metabolic changes, which
collectively lead to a leaner phenotype. A deeper understanding of these changes
may make it possible to develop new strategies against obesity.





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