TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes

Chen, Jicui; Ren, Jianmin; Jing, Qing-ping; Lu, Sumei; Zhang, Yuchao; Liu, Yuantao; Cong, Yu; Gao, Peng; Zong, Chen; Li, Xia; Wang, Xiangdong

doi:10.1002/jcp.24952

Cited by 17 publications

(10 citation statements)

References 29 publications

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“…Since TSHR is detected in preadipocytes and adipocytes, 58, 59 and was shown to participate in adipogenesis, 60 disruption in this gene was already associated with body weight and energy consumption problems. 61 Chen et al 62 demonstrated that increased TSHR inhibits FASN (fatty acid synthase) expression or energy storage in mature adipocytes, showing that impairments in TSH/TSHR signaling could participate in the development of obesity. In the same way, the DGKG (Diacylglycerol Kinase Gamma) gene, that had been associated with chronic stress 63 and obesity, 64 was found upregulated in AN-neurons.…”

Section: Discussionmentioning

confidence: 99%

Modeling anorexia nervosa: transcriptional insights from human iPSC-derived neurons

et al. 2017

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Anorexia nervosa (AN) is a complex and multifactorial disorder occurring predominantly in women. Despite having the highest mortality among psychiatric conditions, it still lacks robust and effective treatment. Disorders such as AN are most likely syndromes with multiple genetic contributions, however, genome-wide studies have been underpowered to reveal associations with this uncommon illness. Here, we generated induced pluripotent stem cells (iPSCs) from adolescent females with AN and unaffected controls. These iPSCs were differentiated into neural cultures and subjected to extensive transcriptome analysis. Within a small cohort of patients who presented for treatment, we identified a novel gene that appears to contribute to AN pathophysiology, TACR1 (tachykinin 1 receptor). The participation of tachykinins in a variety of biological processes and their interactions with other neurotransmitters suggest novel mechanisms for how a disrupted tachykinin system might contribute to AN symptoms. Although TACR1 has been associated with psychiatric conditions, especially anxiety disorders, we believe this report is its first association with AN. Moreover, our human iPSC approach is a proof-of-concept that AN can be modeled in vitro with a full human genetic complement, and represents a new tool for understanding the elusive molecular and cellular mechanisms underlying the disease.

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Section: Discussionmentioning

confidence: 99%

Modeling anorexia nervosa: transcriptional insights from human iPSC-derived neurons

et al. 2017

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“…Studies have proven that HUVECs can express TSHR, which is a g -protein-coupled cell surface protein receptor [ 35 , 36 ]. The TSHR signaling pathway is not only activated in thyroid epithelium, but is also functional in other cells, such as aorta cells [ 14 ], adipocytes [ 37 ], HUVECs [ 15 ], and fibrocytes [ 36 ]. It activates cAMP and the phosphoinositide 3-kinase (PI3K) pathway [ 38 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Thyrotropin on Osteopontin, Integrin αvβ3, and VCAM-1 in the Endothelium via Activation of Akt

Yan

Jiang

Lai

et al. 2016

IJMS

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Numerous epidemiological studies have shown that subclinical hypothyroidism (SCH) can impair endothelial function and cause dyslipidemia. Studies have evaluated the effects of thyroid stimulating hormone (TSH) on endothelial cells, but the mechanism underlying the proatherosclerotic effect of increased TSH levels remains unclear. In the present study, SCH rat models were established in thyroidectomized Wistar rats that were given l-T4 daily. The results showed that in vivo, the expression of osteopontin (OPN) vascular cell adhesion molecule (VCAM-1), and levels of integrin αvβ3 in the aortic tissue in SCH and Hypothyroidism (CH) groups was higher than in the control group. However, the effect in the SCH group was higher than in the CH group. In vitro, results showed that different concentration and time gradients of TSH stimulation could increase the expression of OPN, VCAM-1, and integrin αvβ3, and this was accompanied by extracellular signal regulated kinase 1/2 (Erk1/2) and Akt activation in human umbilical vein endothelial cells (HUVECs). TSH induced elevation of these proatherosclerotic factors was partially suppressed by a specific Akt inhibitor but not by a specific Erk inhibitor. Findings suggested that the endothelial dysfunction caused by SCH was related to increased proatherosclerotic factors induced by TSH via Akt activation.

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“…Fasn is a fatty-acid synthase, which may target endothelial nitric-oxide synthase (eNOS) in the plasma membrane by adding palmitate to eNOS; in this scenario, eNOS could generate NO in vascular tissue, and, in its absence, NO could decrease vasodilatation effectively leading to limb/nerve ischemia and macroangiopathy in T2DM [29]. Prkar2a is known to be a key upstream regulatory factor for Fasn [30, 32]. Three proteins (Gnas, Myh11, and Myh6) were found to be involved in vascular smooth muscle contraction, which is associated with vascular ischemia and poor local blood flow in macroangiopathy in T2DM [24].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Effects and Mechanisms of Mai Tong Formula on Lower Limb Macroangiopathy in a Spontaneous Diabetic Rat Model

Gong

Yuan

Liu

et al. 2016

Journal of Diabetes Research

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A new Chinese herbal formula called Mai Tong Formulae (MTF) has recently been used to treat lower limb macroangiopathy in type 2 diabetes mellitus (T2DM) patients. In this study, we investigated the effect of MTF on lower limb macroangiopathy in a spontaneous diabetic rat model (GK rats). We found that MTF treatment significantly reduced serum fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), IL6, and VEGF and increased serum insulin in this model. Histological and ultrastructural observations showed that MTF treatment significantly reduced vascular endothelial cell shedding and improved endothelium injuries. We further detect proteome alteration following MTF treatment. 25 differential proteins (DPs) abnormally expressed in GK rats were normalized by MTF treatment. These DPs significantly are enriched in biological processes and pathways that regulate muscle contraction and cGMP-PKG signaling pathway and so on. Additional protein-protein interaction (PPI) network analyses of the DPs showed that Fasn and Prkar2a are involved in the AMPK signaling pathway, and Gnas, Myh11, and Myh6 are involved in vascular smooth muscle contraction; these 5 DPs were validated by Western blotting. These results indicate that MTF treatment effectively treats lower limb macroangiopathy by regulating key proteins involved in AMPK signaling pathway and vascular smooth muscle contraction.

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TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes

Cited by 17 publications

References 29 publications

Modeling anorexia nervosa: transcriptional insights from human iPSC-derived neurons

Modeling anorexia nervosa: transcriptional insights from human iPSC-derived neurons

Effect of Thyrotropin on Osteopontin, Integrin αvβ3, and VCAM-1 in the Endothelium via Activation of Akt

Investigation of the Effects and Mechanisms of Mai Tong Formula on Lower Limb Macroangiopathy in a Spontaneous Diabetic Rat Model

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