Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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).

Conclusion

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.

Related collections

Most cited references 18

Record: found
Abstract: found
Article: not found

A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves' ophthalmopathy

Seema Kumar, Sarah Nadeem, Marius Stan … (2011)

Graves' ophthalmopathy (GO) is characterized by expanded volume of the orbital tissues associated with elevated serum levels of TSH receptor (TSHR) autoantibodies. Because previous studies have demonstrated evidence of adipogenesis within the GO orbit, we sought to determine whether M22, a human monoclonal antibody directed against TSHR, enhances adipogenesis in orbital fibroblasts from patients with GO and, if so, to identify signaling mechanisms involved. GO orbital fibroblast cultures (n=10) were treated for 10 days with bovine TSH (1 or 10·0 U/l) or M22 (1 or 10 ng/ml) in serum-free adipocyte differentiation medium. Some cultures also received a phosphoinositide 3-kinase (PI3K) inhibitor or an inhibitor of cAMP production. In other experiments, confluent cultures (n=8) were treated for between 1 and 30 min with TSH (0·1–10·0 U/l) or M22 (0·1–100 ng/ml) with measurement of cAMP production or levels of phosphorylated AKT (pAKT). We found levels of adiponectin, leptin, and TSHR mRNA to be increased in GO cultures treated for 10 days with either M22 (2·6 mean fold ±0·7; P=0·03) or TSH (13·2±5·8-fold, P=0·048). In other studies, M22 and TSH stimulated cAMP production and pAKT levels in GO cells. Inhibition of PI3K activity during 10 days in culture decreased the levels of M22-stimulated mRNA encoding adiponectin (67±12%; P=0·021), as well as adiponectin and CCAAT/enhancer-binding protein α protein levels. In conclusion, M22 is a pro-adipogenic factor in GO orbital preadipocytes. This antibody appears to act via the PI3K signaling cascade, suggesting that inhibition of PI3K signaling may represent a potential novel therapeutic approach in GO.

0 comments Cited 43 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Presence of thyrotropin receptor in hepatocytes: not a case of illegitimate transcription

Wei Zhang, Li-min Tian, Yong-Liang Han … (2009)

The function of thyrotropin (TSH) in the thyroid gland is mediated by thyrotropin receptor (TSHR). In addition to the thyroid, TSHR expression has been described in some non-thyroidal tissues, although it is uncertain whether TSHR is present in hepatocytes. One study has reported hepatic expression of TSHR mRNA, but this was considered to be because of illegitimate transcription, and there has not been a study investigating its protein expression and function in hepatocytes. Here, we examined the expression of TSHR in human and rat liver tissues, as well as human normal hepatocyte cell line L-02. Our results demonstrated that hepatic TSHR mRNA could be detected and had the same sequence as that of thyroid-derived mRNA. TSHR protein was also expressed and mainly located in the hepatocyte cell membrane. Moreover, bovine TSH and immunoglobulin from sera of patients with Graves’ disease stimulated cAMP production in these cells. Taken together, these data show that TSHR is present and functional in hepatocytes, and this expression is not a case of illegitimate transcription. Given the pivotal role of the liver in body metabolism and many human diseases, our findings provide important implications for a potentially novel physiopathological role of TSH via acting on the TSHR in hepatocytes besides its classical role in regulating the thyroid function.

0 comments Cited 34 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse.

Swan Thung, De-Zhu Li, Simon E. Fisher … (2002)

Advanced glycation end products (AGEs), known promoters of diabetic complications, form abundantly in heated foods and are ingested in bioreactive forms. To test whether dietary AGEs play a role in the progression of insulin resistance, C57/BL/KsJ db/db mice were randomly placed for 20 weeks on a diet with either a low AGE content (LAD) or a 3.4-fold higher content of AGE (high AGE diet [HAD]), including (epsilon)N-carboxymethyllysine (CML) and methylglyoxal (MG). LAD-fed mice showed lower fasting plasma insulin levels throughout the study (P = 0.01). Body weight was reduced by approximately 13% compared with HAD-fed mice (P = 0.04) despite equal food intake. LAD-fed mice exhibited significantly improved responses to both glucose (at 40 min, P = 0.003) and insulin (at 60 min, P = 0.007) tolerance tests, which correlated with a twofold higher glucose uptake by adipose tissue (P = 0.02). Compared with the severe hypertrophy and morphological disorganization of islets from HAD-fed mice, LAD-fed mice presented a better-preserved structure of the islets. LAD-fed mice demonstrated significantly increased plasma HDL concentrations (P < 0.0001). Consistent with these observations, LAD-fed mice exhibited twofold lower serum CML and MG concentrations compared with HAD-fed mice (P = 0.02). These results demonstrate that reduced AGE intake leads to lower levels of circulating AGE and to improved insulin sensitivity in db/db mice.

0 comments Cited 26 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Lipids Health Dis

Title: Lipids in Health and Disease

Publisher: BioMed Central

ISSN (Electronic): 1476-511X

Publication date Collection: 2012

Publication date (Electronic): 30 January 2012

Volume: 11

Page: 17

Affiliations

[1 ]The Institute of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012

[2 ]Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Jinan, China, 250021

[3 ]Department of Endocrinology, the Second Hospital of Shandong University, Jinan, China, 250033

[4 ]Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China, 250021

[5 ]Department of Nutrition Sciences, University of Alabama at Birmingham, AL35294, USA

Article

Publisher ID: 1476-511X-11-17

DOI: 10.1186/1476-511X-11-17

PMC ID: 3285521

PubMed ID: 22289392

SO-VID: 892f8388-95dd-4338-a990-8baa4827ae2f

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity

Read this article at

Abstract

Background

Methods

Results

Conclusion

Related collections

A Sustainable Future

Most cited references 18

A stimulatory TSH receptor antibody enhances adipogenesis via phosphoinositide 3-kinase activation in orbital preadipocytes from patients with Graves' ophthalmopathy

Presence of thyrotropin receptor in hepatocytes: not a case of illegitimate transcription

Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 598

Cited by 38

Most referenced authors 193