TSH increases synthesis of hepatic ATP-binding cassette subfamily A member 1 in hypercholesterolemia

Biochem Biophys Res Commun. 2016 Jul 22;476(2):75-81. doi: 10.1016/j.bbrc.2016.05.054. Epub 2016 May 11.

Abstract

Epidemiological evidence suggests that thyrotropin (TSH) levels are closely correlated with the severity of hypercholesterolemia. Reverse cholesterol transfer (RCT) plays an important role in regulating bloodcholesterol. However, the molecular mechanism of hypercholesterolemia in subclinical hypothyroidism (SCH) has not been fully clarified. The SCH mouse model, which is characterized by elevated serum TSH but not thyroid hormone levels, demonstrated a significant increase in plasma cholesterol compared with controls. Interestingly, Tshr KO mice, with normal thyroid hormone levels after thyroid hormone supplementation, showed lower plasma cholesterol levels compared with their wild-type littermates. ATP binding cassette subfamily A member 1(ABCA1) is a member of the ABC superfamily, which induces transfer of intracellular cholesterol to extracellular apolipoprotein. TSH upregulated hepatic ABCA1 to promote the efflux of intercellular cumulative cholesterol, resulting in increased plasma cholesterol. These data might partially explain the pathogenesis of hypercholesterolemia in SCH.

Keywords: ABCA1; Hypercholesteremia; SCH mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics*
  • ATP Binding Cassette Transporter 1 / metabolism
  • Animals
  • Cholesterol / blood
  • Cholesterol / metabolism
  • Hep G2 Cells
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism*
  • Hypothyroidism / blood
  • Hypothyroidism / complications
  • Hypothyroidism / genetics
  • Hypothyroidism / metabolism*
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Thyrotropin / metabolism*
  • Up-Regulation*

Substances

  • ABCA1 protein, human
  • ABCA1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • Thyrotropin
  • Cholesterol