TSHBmRNA is linked to cholesterol metabolism in adipose tissue

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 () 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 mRNA were also examined. The bidirectional relationship between cholesterol and were studied in isolated human adipocytes. 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,-stearoyl-d-sphingosine, and GlcCer(18:0, 24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased mRNA in human AT, whereas excess cholesterol up-regulated mRNA in human adipocytes. In addition, recombinant human TSH α/β administration resulted in increased mRNA levels in human adipocytes. In mice, subcutaneous AT expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of 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. mRNA is linked to cholesterol metabolism in adipose tissue.

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

“…The fact that the associations between TC and LDL-C were observed in patients with GO of recent onset points to the potential involvement of autoimmune process per se and to the possibility that TC is involved in the induction of oxidative stress which plays an important role in the pathogenesis of GO. Meanwhile, the recent finding that TSH-β mRNA was positively associated with serum TC and LDL-C and, moreover, that it was detected in adipose tissue ( 30 ), might partially substantiate these results and hypotheses.…”

Obesity and Thyroid Axis

“…TSH-TSHR signaling plays a regulatory role in this process. TSHR mRNA levels in mature adipocytes were 100-fold greater than in preadipocytes in the in vitro experiment [ 22 ]. It is important to realize that, in certain situations, adipogenesis slows down.…”

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

“…Lipidomic analyses were performed as described elsewhere [16], in a subsample of 12 consecutive subjects from Cohort 1. Briefly, 35-50 mg samples of SAT (n=12) were homogenized in 20 volumes (v/w) cold methanol (with BHT 1 µM) (1:20 w:v) at 4ºC.…”

“…Given the recent description of TSHB mRNA in human AT [16], the potential associations of TSHB mRNA with markers of AT senescence were explored. Then, the impact of recombinant human (rh)TSH in human adipocytes and of chronic serum TSH elevation (induced by aminotriazole) on AT senescence in rats was evaluated.…”