Regional decrease of subcutaneous adipose tissue in patients with type 2 familial partial lipodystrophy is associated with changes in thyroid hormone metabolism.
BACKGROUND
Familial partial lipodystrophy of the Dunnigan type (FPLD2) presents with a decrease of subcutaneous adipose tissue (SAT) in the limbs and trunk. As thyroid hormones (TH) play an important role in adipogenesis, we studied if SAT from subjects with FPLD2 have changes in the gene expression levels of monocarboxylate transporter 8 (MCT8), a TH transporter, and TH nuclear receptors and in iodothyronine deiodinases (DIOs) expression and activities that could affect TH bioavailability and action in white adipose tissue.


METHODS
Seven subjects with FPLD2 and 10 healthy controls were studied. Two biopsies of SAT were obtained from each subject, one near the umbilicus and the other from the thigh. Expression of MCT8, DIO2, DIO3, THRA1, THRB1, and RXRG mRNAs were quantified by real-time polymerase chain reaction. DIO1 and DIO2 activities in adipose tissue homogenates were determined. Serum thyroid-stimulating hormone and TH levels were measured by chemiluminescence.


RESULTS
Subjects with FPLD2 had lower levels of MCT8 mRNA expression in the thigh than in the abdomen SAT, and lower than in the abdomen and thigh SAT from control subjects. FPLD2 subjects also had higher DIO2 expression and activity in the thigh than in the abdomen SAT and higher than in controls.


CONCLUSIONS
Thigh SAT from subjects with FPLD2 has lower expression of MCT8 and higher DIO2 expression and activity than abdominal SAT, suggesting that changes in local TH metabolism may occur in areas with lipoatrophy. DIO2 expression and activity in SAT suggest that DIO2 can regulate the metabolism and action of TH in human white adipose tissue.
Lado-Abeal
Joaquin
J
Department of Medicine, University of Santiago de Compostela , Santiago de Compostela, Spain. joaquin.lado@ttuhsc.edu
Calvo
Rosa-Maria
RM
Victoria
Berta
B
Castro
Isabel
I
Obregon
Maria Jesus
MJ
Araujo-Vilar
David
D
D050153:Abdominal Fat / Q000201:enzymology; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D052496:Lipodystrophy, Familial Partial / Q000473:pathology*; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology*; D027981:Symporters; D013848:Thigh; D013963:Thyroid Hormones / Q000378:metabolism*; D000097564:Iodothyronine Deiodinase Type II
D007453:Iodide Peroxidase; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; D027981:Symporters; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II; C090735:SLC16A2 protein, human