Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH-induced lipolysis

Elgadi, Aziz; Zemack, Helen; Marcus, Claude; Norgren, Svante

doi:10.1016/j.bbrc.2010.02.042

Cited by 44 publications

(28 citation statements)

References 35 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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Background/Aims: Thyroid-stimulating hormone (TSH) is affected in obesity and might influence metabolic risk. It is unclear what mechanisms cause elevated TSH in obesity. We aimed to investigate TSH status within the normal range and the association of TSH with degree of obesity and metabolic parameters in children with obesity. Methods: A total of 3,459 children, aged 3.0–17.9 years, were identified in the Swedish Childhood Obesity Treatment Registry, BORIS. Age, gender, TSH, free triiodothyronine (fT3), free thyroxine (fT4), body mass index standard deviation scores (BMI SDS), as well as variables of lipid and glucose metabolism were examined. Results: Children with high-normal TSH (>3.0 mU/L) (28.8%) had higher BMI SDS compared to children with low-normal TSH (<3.0 mU/L) (p < 0.001). Multivariable regression analysis adjusted for age and gender showed that TSH levels were associated with BMI SDS (β: 0.21, 95% CI: 0.14–0.28, p < 0.001). Associations of thyroid hormones with markers of lipid and glucose metabolism were observed, where TSH was associated with fasting insulin, HOMA (homeostatic model assessment of insulin resistance), total cholesterol, and triglycerides. Conclusions: A positive association between TSH levels and BMI SDS was seen in children with obesity. Associations of TSH and free thyroid hormones with glucose metabolism indicated that TSH might be one of several factors acting to determine body weight and obesity co-morbidities, although the underlying mechanism remains unclear.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…TSH has been linked to significant extrathyroidal effects, namely, lipolysis (23,24) and control of bone mass (25)(26)(27). Interestingly, the pit-D2 KO animals exhibited decreased fat mass and normal bone mass (Table 2), which could potentially shed some light on the roles played by TSH in these processes.…”

Section: Figurementioning

confidence: 98%

Coordination of hypothalamic and pituitary T3 production regulates TSH expression

et al. 2013

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Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3′-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary-and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40% reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.

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“…Tshr -KO mice have been used commonly as an effective method in the research of TSH and TSHR ( 31,32 ). The Tshr -KO mice were hypothyroid because of being unable to respond to pituitary TSH.…”

Section: Note Added In Proofmentioning

confidence: 99%

Thyroid-stimulating hormone decreases HMG-CoA reductase phosphorylation via AMP-activated protein kinase in the liver

Zhang

Song

Feng

et al. 2015

Journal of Lipid Research

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Supplementary key words adenosine 5 ′ -monophosphate-activated protein kinase • cholesterol • hydroxy-methylglutaryl coenzyme A reductaseThe liver plays a vital role in regulating cholesterol homeostasis in the body. HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol biosynthesis ( 1 ), so its activity is instrumental in controlling de novo cholesterol synthesis. To maintain cholesterol homeostasis, HMGCR could be regulated by multiple mechanisms such as transcription, translation ( 2 ), enzyme degradation rate ( 3 ), phosphorylation-dephosphorylation ( 4 ), and feedback inhibition ( 5 ). Hormones could regulate the expression of HMGCR by acting at different levels. For example, glucocorticoids act at a posttranslational level ( 1 ), whereas insulin reportedly affects both the transcriptional and posttranslational processes ( 6 ). Recently, Wu et al. ( 7 ) found that the changes of the phosphorylated HMGCR play an important role in regulation of the hepatic cholesterol biosynthesis process. The site of phosphorylation on HMGCR has been identifi ed as serine 871 in rodents ( 8 ) and serine 872 in humans ( 9 ). The HMGCR is physiologically present in the cell in unphosphorylated active form and phosphorylated inactive form. In general, phosphorylation of HMGCR leads to inactivation of the enzyme, while dephosphorylation activates it. The ratio of the phosphorylated form to total form indicates an inactivation state of HMGCR. Abstract

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Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH-induced lipolysis

Cited by 44 publications

References 35 publications

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

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

Coordination of hypothalamic and pituitary T3 production regulates TSH expression

Thyroid-stimulating hormone decreases HMG-CoA reductase phosphorylation via AMP-activated protein kinase in the liver

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