Format

Send to

Choose Destination
FASEB J. 2017 Oct;31(10):4482-4491. doi: 10.1096/fj.201700161R. Epub 2017 Jun 23.

TSHB mRNA is linked to cholesterol metabolism in adipose tissue.

Author information

1
Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Girona, Spain.
2
Department of Medicine, Universitat de Girona, Girona, Spain.
3
Division of Diabetes, Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
4
Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
5
Nutrició i Envelliment (NUTREN)-Nutrigenomics, Institut de Recerca Biomèdica de Lleida (IRBLLEIDA)-University of Lleida, Científic i Tecnològic Agroalimentari de Lleida (PCiTAL), Lleida, Spain.
6
Department of Medicine, University of Leipzig, Leipzig, Germany.
7
Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Girona, Spain; jmfreal@idibgi.org.

Abstract

Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid-stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross-sectionally, AT TSH-β (TSHB) mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT TSHB mRNA were also examined. The bidirectional relationship between cholesterol and TSHB were studied in isolated human adipocytes. TSHB mRNA was consistently detected in AT from euthyroid subjects, and positively associated with serum total- and LDL-cholesterol, and with AT-specific cholesterol metabolism-associated lipids [arachidonoyl cholesteryl ester, C8-dihydroceramide, N-stearoyl-d-sphingosine, and GlcCer(18:0, 24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased TSHB mRNA in human AT, whereas excess cholesterol up-regulated TSHB mRNA in human adipocytes. In addition, recombinant human TSH α/β administration resulted in increased HMGCR mRNA levels in human adipocytes. In mice, subcutaneous AT Tshb expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of TSHB as a paracrine factor that is modulated in parallel with cholesterol metabolism in human AT.-Moreno-Navarrete, J. M., Moreno, M., Ortega, F., Xifra, G., Hong, S., Asara, J. M., Serrano, J. C. E., Jové, M., Pissios, P., Blüher, M., Ricart, W., Portero-Otin, M., Fernández-Real, J. M. TSHB mRNA is linked to cholesterol metabolism in adipose tissue.

KEYWORDS:

HMGCR; adipocyte; lipidomic; obesity; statins

PMID:
28646016
PMCID:
PMC5602896
DOI:
10.1096/fj.201700161R
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center