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

Cell Physiol Biochem. 2018;51(1):142-153. doi: 10.1159/000495170. Epub 2018 Nov 16.

Abstract

Background/aims: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence.

Methods: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DBC1, TP53, TNF (real-time PCR), telomere length (Telo TAGGG Telomere Length Assay) and lipidomics (liquid chromatography mass spectrometry)] were analysed in subcutaneous (SAT) and visceral (VAT) AT from euthyroid subjects. The chronic effects of TSH were also investigated in AT from hypothyroid rats and after recombinant human TSH (rhTSH) administration in human adipocytes.

Results: Both VAT and SAT TSHB gene expression negatively correlated with markers of AT cellular senescence (BAX, DBC1, TP53, TNF gene expression and specific glucosylceramides) and positively associated with telomere length. Supporting these observations, both rhTSH administration in human adipocytes and increased TSH in hypothyroid rats resulted in decreased markers of cellular senescence (Bax and Tp53 mRNA) in both gonadal and subcutaneous white adipose tissue.

Conclusion: These data point to a possible role of TSH in AT cellular senescence.

Keywords: Adipose tissue; Cellular senescence; Euthyroidism; Hypothyroidism; Thyroid-stimulating hormone.

MeSH terms

  • Adult
  • Animals
  • Biomarkers / metabolism
  • Blood Glucose / analysis
  • Cellular Senescence* / drug effects
  • Cellular Senescence* / genetics
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypothyroidism / pathology*
  • Hypothyroidism / veterinary
  • Intra-Abdominal Fat / cytology
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism*
  • Male
  • Middle Aged
  • Rats
  • Rats, Sprague-Dawley
  • Subcutaneous Fat / cytology
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism*
  • Telomere Homeostasis
  • Thyrotropin / genetics
  • Thyrotropin / metabolism
  • Thyrotropin / pharmacology
  • Thyrotropin, beta Subunit / genetics
  • Thyrotropin, beta Subunit / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Biomarkers
  • Blood Glucose
  • Thyrotropin, beta Subunit
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Thyrotropin