title: Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity.
abstract: BACKGROUND
  Obesity is known to be associated with higher risks of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Thyroid-stimulating hormone (TSHR) is the receptor for thyroid-stimulating hormone (TSH, or thyrotropin), the key regulator of thyroid functions. The expression of TSHR, once considered to be limited to thyrocytes, has been so far detected in many extrathyroidal tissues including liver and fat. Previous studies have shown that TSHR expression is upregulated when preadipocytes differentiate into mature adipocytes, suggestive of a possible role of TSHR in adipogenesis. However, it remains unclear whether TSHR expression in adipocytes is implicated in the pathogenesis of obesity.
  
  
  METHODS
  In the present study, TSHR expression in adipose tissues from both mice and human was analyzed, and its association with obesity was evaluated.
  
  
  RESULTS
  We here showed that TSHR expression was increased at both mRNA and protein levels when 3T3-L1 preadipocytes were induced to differentiate. Knockdown of TSHR blocked the adipocyte differentiation of 3T3-L1 preadipocytes as evaluated by Oil-red-O staining for lipid accumulation and by RT-PCR analyses of PPAR-γ and ALBP mRNA expression. We generated obesity mice (C57/BL6) by high-fat diet feeding and found that the TSHR protein expression in visceral adipose tissues from obesity mice was significantly higher in comparison with the non-obesity control mice (P < 0.05). Finally, the TSHR expression in adipose tissues was determined in 120 patients. The results showed that TSHR expression in subcutaneous adipose tissue is correlated with BMI (body mass index).
  
  
  CONCLUSIONS
  Taken together, these results suggested that TSHR is an important regulator of adipocyte differentiation. Dysregulated expression of TSHR in adipose tissues is associated with obesity, which may involve a mechanism of excess adipogenesis.
authors.affiliation: The Institute of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012.
authors.forename: Sumei
authors.initials: S
authors.lastname: Lu
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Guan
authors.forename: Yuantao
authors.initials: Y
authors.lastname: Liu
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Fu
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis; D000818:Animals; D015992:Body Mass Index; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic
chemical_list: D011989:Receptors, Thyrotropin