scholarly journals Leptin Regulates Hypothalamus-Pituitary-Thyroid Axis via TRH in Energy Expenditure During Fasting: The Study on TRH Deficient Mouse

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A851-A851
Author(s):  
Yuri Kondo ◽  
Atsushi Ozawa ◽  
Takuya Watanabe ◽  
Masayuki Yoshioka ◽  
Sayaka Yamada ◽  
...  

Abstract Objectives: The hypothalamic-pituitary-thyroid (HPT) axis plays a significant role in the regulation of energy expenditure. Previous reports demonstrated that thyroid hormones are critically involved in metabolic process, and hypothyroidism was induced by fasting. The mechanism by which TRH neurons sense alterations in peripheral energy stores is supposed to be regulated by leptin, an adipose tissue-derived hormone. Leptin was initially considered as a hormone to prevent obesity, it was later showed that the major role of leptin is to signal the switch from the fed to the starved state at the hypothalamic level. Recently, we generated TRH-deficient mice (TRH-/-). The mice exhibit tertiary/central hypothyroidism with characteristic elevation of serum TSH level and diminished TSH biological activity. In this study, we used TRH-/- to investigate the physiological role of TRH in fasting energy expenditure, including the mechanism regulated by leptin. Methods: Twelve-week-old male F2 hybrid ICR mice were used in this study. (1) Wild-type mice (WT) and TRH-/- were fasted up to 50 hrs. Blood samples were collected from tail veins at various points. Anterior pituitary samples were obtained from euthanized mice before and after 16 hrs fasting. (2) Serum free T4 (FT4) and TSH levels assessed. (3) The expression level of TSHβ mRNA in anterior pituitary were detected using qPCR assays. (4) We repeated these experiments using mice with leptin administration; leptin (0.5μg/g•BW) was administrated every 6 hours starting at after 2 hours fasting. Results: In WT, the level of FT4 was decreased chronologically during fasting to approximately 50% at 50 hrs after fasting. Serum TSH decreased to 70% and the expression level of TSHβ mRNA in anterior pituitary also decreased to 30% compared to before fasting. Administration of leptin recovered the level of FT4 to basal level. However, the level of serum TSH and TSHβ mRNA in pituitary were not recovered to basal levels. By contrast, in TRH-/-, the level of FT4 were also decreased after fasting indicating that the decrease of FT4 by fasting was independent of TRH. However, the level of FT4 was not recovered by leptin suggesting that the recovery of FT4 by leptin was TRH dependent. Serum TSH level decreased to 75% after fasting, and no recovery to basal level with leptin administration was observed in TRH-/- same as WT. In TRH-/-, the pituitary TSHβ mRNA expression level was about 50% of WT before fasting. It did not correlate with the serum TSH level. In addition, no increase in TSHβ mRNA expression level by leptin administration was observed in TRH-/-. These findings suggested that the TSHβ mRNA expression level in the pituitary is completely TRH-dependent in TRH-/-. Conclusion: Fasting-induced hypothyroxinemia was independent of TRH. Leptin regulates H-P-T axis via TRH during fasting-induced energy expenditure. Leptin may modulate the biological activity of TSHβ.

Author(s):  
Yingying Yue ◽  
Haitang Jiang ◽  
Yingying Yin ◽  
Yuqun Zhang ◽  
Jinfeng Liang ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rehan Khan ◽  
Ananya Palo ◽  
Manjusha Dixit

AbstractFRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed that FRG1 mRNA expression is associated with overall survival (OS) in certain cancers, but the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 mRNA expression groups, but the difference was not prominent in breast, lung, and liver cancers. We hypothesized that FRG1 expression level could affect the functionality of the correlated genes or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, HIPPIE, Gene Ontology, and DAVID (KEGG) were used to deduce FRG1 associated pathways. In breast, lung, and liver cancers, we found a distinct difference in the OS between the low and high FRG1 mRNA expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups showed a significant difference in the FRG1 mRNA expression level and OS. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 mRNA expression level on these genes by qRT-PCR supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators, which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis.


Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 595
Author(s):  
Ji Young Park ◽  
Sung-Bae Park ◽  
Heechul Park ◽  
Jungho Kim ◽  
Ye Na Kim ◽  
...  

There have been few reports on the kinetics of hemodialyzed (HD) patients’ immune responses in latent tuberculosis infection (LTBI). Therefore, in the present study, messenger ribonucleic acid (mRNA) expression levels of nine immune markers were analyzed to discriminate between HD patients with LTBI and healthy individuals. Nine cytokines and chemokines were screened through relative mRNA expression levels in whole blood samples after stimulation with Mycobacterium tuberculosis (MTB)-specific antigens from HD patients with LTBI (HD/LTBI), HD patients without LTBI, and healthy individuals, and results were compared with the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. We confirmed that the C-C motif chemokine 11 (CCL11) mRNA expression level of the HD/LTBI group was significantly higher than the other two groups. Especially, the CCL11 mRNA expression level of the >0.7 IU/mL group in the QFT-GIT test was significantly higher than the <0.2 IU/mL group in the QFT-GIT test and the 0.2–0.7 IU/mL group in the QFT-GIT test (p = 0.0043). The present study reveals that the relative mRNA expression of CCL11 was statistically different in LTBI based on the current cut-off value (i.e., ≥0.35 IU/mL) and in the >0.7 IU/mL group. These results suggest that CCL11 mRNA expression might be an alternative biomarker for LTBI diagnosis in HD patients.


2017 ◽  
Vol 158 (24) ◽  
pp. 929-937
Author(s):  
Krisztián Kovács ◽  
Barna Vásárhelyi ◽  
Katalin Mészáros ◽  
Attila Patócs ◽  
Gellért Karvaly

Abstract: Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929–937.


2010 ◽  
Vol 9 (11) ◽  
pp. 1659-1666 ◽  
Author(s):  
Er-lin LI ◽  
Xin-hua XIE ◽  
Ye-fen XU ◽  
Zhuang XIE ◽  
Ling CHEN ◽  
...  

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