Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH-induced lipolysis.
BACKGROUND
The primary function of TSH is to activate TSH receptors (TSHr) in the thyroid gland and thereby stimulate thyroid hormone synthesis and secretion. TSHr are also expressed in other organs, but their physiological importance is still unclear. We have previously shown that TSHr, expressed in adipocytes, are of potential importance for lipolysis and extrauterine adaptation of the neonate.


METHODS
To further study the role of TSHr in adipocytes we selectively removed the TSHr gene in mice adipocytes by using the Cre-loxP recombination system (B6.Cg-Tg (Fabp4-Cre) 1Rev/J. TSHr knockout (KO) newborn mice were phenotypically characterized. Isolated adipocytes from 8-week-old male mice were studied in term of adipocyte size and metabolism.


RESULTS
Mice lacking TSHr in adipocytes were apparently normal at birth and no differences in thyroid gland function or histology were observed. Sensitivity to TSH-induced lipolysis was ten times lower in adipocytes from targeted animals compared to wild-type. This indicates that adipocytes from targeted animals are refractory to stimulation of physiological concentrations of TSH. Catecholamine-induced lipolysis and insulin-induced inhibition of lipolysis were unaltered. Adipocyte size was increased in the targeted animals. Basal lipolysis was increased as an effect of the increased adipocyte size.


CONCLUSIONS
Our results indicate that adipocyte TSHr under normal conditions affects adipocyte growth and development.
Department of Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institutet, Endocrine Research Unit B62, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden. Aziz.Elgadi@ki.se
Aziz
A
Elgadi
Helen
H
Zemack
Claude
C
Marcus
Svante
S
Norgren
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D048429:Cell Size; D008066:Lipolysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000502:physiology*; D013972:Thyrotropin / Q000494:pharmacology / Q000502:physiology*
D011989:Receptors, Thyrotropin; D013972:Thyrotropin