TSH stimulates adipogenesis in mouse embryonic stem cells

Abstract

Although TSH is the main regulator of thyroid growth and function, TSH binding activity in fat has long been reported. Since the TSH receptor (TSHR) has been detected in both preadipocytes and adipocytes, we hypothesized that it may play a role in adipose differentiation. Here, we use an in vitro model of adipogenesis from mouse embryonic stem (ES) cells to define TSH function. Directed differentiation of ES cells into the adipose lineage can be achieved over a 3-week period. Although adipocyte differentiation is initiated early in the development of cultured ES cells, TSHR up-regulation is precisely correlated with terminal differentiation of those adipocytes. The adipocytes express TSHR on the cell surface and respond to TSH with increased intracellular cAMP production, suggesting the activation of the protein kinase A signaling pathway. To determine whether TSH impacts adipogenesis, we examined how adipocytes responded to TSH at various points during their differentiation from cultured ES cells. We found that TSH greatly increases adipogenesis when added in the presence of adipogenic factors. More importantly, our data suggest that TSH also stimulates adipogenesis in cultured ES cells even in the absence of adipogenic factors. This finding provides the first evidence of TSH being a pro-adipogenic factor that converts ES cells into adipocytes. It further highlights the potential of ES cells as a model system for use in the study of TSH's role in the regulation of physiologically relevant adipose tissue.

Relationship between Body Mass Index and Thyrotropin in Euthyroid Women: Differences by Smoking, Race and Menopausal Status

“…These findings suggest that variations in TSH concentration, mainly in euthyroid subjects, could lead to body weight changes independent of its effect on thyroid function. In agreement with this finding, TSH receptor has been detected at the surface of both preadipocytes and adipocytes, and it was shown that TSH can directly stimulate preadipocyte differentiation, thereby inducing adipogenesis [25].…”

Thyroid-Stimulating Hormone, Degree of Obesity, and Metabolic Risk Markers in a Cohort of Swedish Children with Obesity

“…Previous studies have confirmed that there might be a direct effect of TSH in the adipose tissue via adipocyte TSH receptors (TSHr) [34, 35] independently of its effect on thyroid function. Previously, TSH acting on TSHr has been shown to be involved in regulating lipolysis in neonates [36], inducing adipogenesis in mouse embryonic stem cells [37], directly stimulating leptin secretion in human adipose tissue [38], and inducing differentiation of preadipocytes [39], supporting the hypothesis that there is a relationship between adipose tissue and TSH. In theory, the regulation of thyroid function could be impaired due to a reduction of TSHr in the adipose tissue of obese individuals.…”

Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients

“…Adipocytes express TSH receptors, and VAT proliferation can take place based on TSH expression in visceral and adipose tissue [30]. TSH may also be capable of increasing adipogenesis in embryonic stem cells [31]. A study has demonstrated that, even within the normal range, increase in TSH in women with no known history of CVD increased fatal coronary incidences [32].…”