Interplay between Thyroid Hormones and Stearoyl-CoA Desaturase 1 in the Regulation of Lipid Metabolism in the Heart

Int J Mol Sci. 2020 Dec 24;22(1):109. doi: 10.3390/ijms22010109.


Stearoyl-CoA desaturase 1 (SCD1), an enzyme that is involved in the biosynthesis of monounsaturated fatty acids, induces the reprogramming of cardiomyocyte metabolism. Thyroid hormones (THs) activate both lipolysis and lipogenesis. Many genes that are involved in lipid metabolism, including Scd1, are regulated by THs. The present study used SCD1 knockout (SCD1-/-) mice to test the hypothesis that THs are important factors that mediate the anti-steatotic effect of SCD1 downregulation in the heart. SCD1 deficiency decreased plasma levels of thyroid-stimulating hormone and thyroxine and the expression of genes that regulate intracellular TH levels (i.e., Slc16a2 and Dio1-3) in cardiomyocytes. Both hypothyroidism and SCD1 deficiency affected genomic and non-genomic TH pathways in the heart. SCD1 deficiency is known to protect mice from genetic- or diet-induced obesity and decrease lipid content in the heart. Interestingly, hypothyroidism increased body adiposity and triglyceride and diacylglycerol levels in the heart in SCD1-/- mice. The accumulation of triglycerides in cardiomyocytes in SCD1-/- hypothyroid mice was caused by the activation of lipogenesis, which likely exceeded the upregulation of lipolysis and fatty acid oxidation. Lipid accumulation was also observed in the heart in wildtype hypothyroid mice compared with wildtype control mice, but this process was related to a reduction of triglyceride lipolysis and fatty acid oxidation. We also found that simultaneous SCD1 and deiodinase inhibition increased triglyceride content in HL-1 cardiomyocytes, and this process was related to the downregulation of lipolysis. Altogether, the present results suggest that THs are an important part of the mechanism of SCD1 in cardiac lipid utilization and may be involved in the upregulation of energetic metabolism that is associated with SCD1 deficiency.

Keywords: SCD1; hypothyroidism; inflammation; lipogenesis; lipolysis; β-oxidation.

MeSH terms

  • Animals
  • Down-Regulation*
  • Gene Expression Regulation, Enzymologic*
  • Lipid Metabolism*
  • Mice
  • Mice, Knockout
  • Myocardium / metabolism*
  • Stearoyl-CoA Desaturase / biosynthesis*
  • Stearoyl-CoA Desaturase / genetics
  • Thyrotropin / genetics
  • Thyrotropin / metabolism*
  • Thyroxine / genetics
  • Thyroxine / metabolism*


  • Thyrotropin
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase
  • Thyroxine