title: TSH increases synthesis of hepatic ATP-binding cassette subfamily A member 1 in hypercholesterolemia.
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.
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Jinan Central Hospital affiliated to Shandong University, Jinan, Shandong, 250021, China.
authors.forename: Cong Cong
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, China. Electronic address: zhouxinli0301@163.com.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhou
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013972:Thyrotropin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D064286:ATP Binding Cassette Transporter 1; D002784:Cholesterol; D013972:Thyrotropin; C577836:ABCA1 protein, human; C577833:Abca1 protein, mouse
keywords: ABCA1; Hypercholesteremia; SCH mice