Ghrelin Receptor in Energy Homeostasis and Obesity Pathogenesis

Li, Ziru; Li, Yin; Zhang, Weizhen

doi:10.1016/b978-0-12-386933-3.00002-9

Cited by 6 publications

(4 citation statements)

References 181 publications

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“…To confirm the loss of GHSR1a, splenic T cells from GHSR1a -/- mice and wide type littermates were analyzed for GHSR expression by PCR [ 24 ]. GHSR1a was detected only in spenic T cells derived from wildtype mice ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Ghrelin Inhibits the Differentiation of T Helper 17 Cells through mTOR/STAT3 Signaling Pathway

Yin

et al. 2015

PLoS ONE

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Enhanced activity of interleukin 17 (IL-17) producing T helper 17 (Th17) cells plays an important role in autoimmune and inflammatory diseases. Significant loss of body weight and appetite is associated with chronic inflammation and immune activation, suggesting the cross talk between immune and neuroendocrine systems. Ghrelin has been shown to regulate the organism immune function. However, the effects of ghrelin on the differentiation of Th17 cells remain elusive. In the present study, we observed the enhanced differentiation of Th17 cells in spleens of growth hormone secretagogue receptor 1a (GHSR1a)-/- mice. Treatment of ghrelin repressed Th17 cell differentiation in a time- and concentration-dependent manner. Phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) was increased in the spleens of GHSR1a-/- mice. Activation of mTOR signaling by injection of Cre-expressiong adenovirus into tuberous sclerosis complex 1 (TSC1) loxp/loxp mice increased the differentiation of Th17 cells in spleen, which was associated with an increment in the phosphorylation of STAT3. Activation of mTOR signaling by leucine or overexpression of p70 ribosome protein subunit 6 kinase 1 (S6K1) activated mTOR signaling in isolated T cells, while reversed the ghrelin-induced inhibition of iTh17 cell differentiation. In conclusion, mTOR mediates the inhibitory effect of ghrelin on the differentiation of Th17 cells by interacting with STAT3.

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Section: Resultsmentioning

confidence: 99%

Ghrelin Inhibits the Differentiation of T Helper 17 Cells through mTOR/STAT3 Signaling Pathway

Yin

et al. 2015

PLoS ONE

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“…mTOR, which is a central regulator of cellular energy metabolism, has been shown to play a key role in the lineage choices between Th17 and Treg cells (19). mTOR inhibition with rapamycin results in the diminished differentiation of Th17 cells but in increase in Treg generation (35,36). We found that GHSR1a deficiency significantly attenuated mTOR phosphorylation, which indicates that GHSR1a plays a role in regulating mTOR activity during T cell differentiation.…”

Section: Discussionmentioning

confidence: 56%

Growth hormone secretagogue receptor deficiency promotes lung cancer growth by affecting the Th17/Treg balance

Wu¹,

Li²,

Qin³

et al. 2021

Ann Transl Med

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Background: Cluster of differentiation 4 (CD4 + ) T cells plays a prominent role in eliminating cancer cells.The balance between T helper (Th)17 and regulatory T (Treg) cells is crucial for optimal immune response and protection against cancer. Growth hormone secretagogue receptor 1a (GHSR1a), a member of the G protein-coupled protein receptor superfamily, plays a critical role in immune cell function. The aim of our study is to investigate the role of GHSR1a in CD4 + T cell differentiation and lung cancer progression. Methods: A subcutaneous lung cancer model was used to examine the role of GHSR1a in controlling tumor growth. Lewis lung carcinoma (LLC) cells were subcutaneously implanted into Ghsr1a −/− mice and wild-type (WT) mice. The ratio of Th17 and Treg in the draining lymph node of Ghsr1a −/− mice and WT tumor-bearing mice was detected by fluorescence-activated cell sorting (FACS). The effect of GHSR1a deficiency on Th17 and Treg cell differentiation was examined using an in vitro differentiation assay. The phosphorylation of mammalian target of rapamycin (mTOR), signal transducer, and activator of transcription (STAT)3 and STAT5 signaling was detected with Western blot. Results: We found that the ablation of GHSR1a resulted in impaired anti-tumor immunity to control lung cancer growth in vivo. We also demonstrated that the deficiency of GHSR1a promoted a shift in the Th17/Treg balance toward enhanced Treg differentiation and inhibited Th17 differentiation both in vivo and in vitro, which suggests that GHSR1a regulates T cell lineage choices between Th17 and Treg cell commitment in the tumor microenvironment. Mechanistically, the deficiency of GHSR1a resulted in reduced phosphorylation in mTOR and STAT3, and increased phosphorylation in STAT5. Conclusions: Our findings showed the important role of GHSR1a in CD4 + T cell differentiation in the context of the lung cancer microenvironment. This research provides a novel molecular target and insights into interventions for the prevention and treatment of lung cancer.

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“…Vitamin D has also been found to enhance the insulin action in cells through the PI3K-dependent insulin signaling [ 103 ]. The activation of IR will stimulate the phosphorylation of tyrosine residues in the insulin receptor substrate (IRS) protein where its key functions is to regulate the PI3K [ 104 ]. Therefore, by modulating the Ir gene and upregulating the IR, vitamin D could indirectly boost the IRS-associated PI3K activity, which is involved in the glucose uptake in insulin-responsive tissues [ 105 ].…”

Section: Mechanisms Underlying the Action Of Vitamin D In Improving I...mentioning

confidence: 99%

Mechanisms Linking Vitamin D Deficiency to Impaired Metabolism: An Overview

Ghozali

Giribabu

Salleh

2022

International Journal of Endocrinology

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Vitamin D deficiency is a common health problem worldwide. Despite its known skeletal effects, studies have begun to explore its extra-skeletal effects, that is, in preventing metabolic diseases such as obesity, hyperlipidemia, and diabetes mellitus. The mechanisms by which vitamin D deficiency led to these unfavorable metabolic consequences have been explored. Current evidence indicates that the deficiency of vitamin D could impair the pancreatic β-cell functions, thus compromising its insulin secretion. Besides, vitamin D deficiency could also exacerbate inflammation, oxidative stress, and apoptosis in the pancreas and many organs, which leads to insulin resistance. Together, these will contribute to impairment in glucose homeostasis. This review summarizes the reported metabolic effects of vitamin D, in order to identify its potential use to prevent and overcome metabolic diseases.

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Ghrelin Receptor in Energy Homeostasis and Obesity Pathogenesis

Cited by 6 publications

References 181 publications

Ghrelin Inhibits the Differentiation of T Helper 17 Cells through mTOR/STAT3 Signaling Pathway

Ghrelin Inhibits the Differentiation of T Helper 17 Cells through mTOR/STAT3 Signaling Pathway

Growth hormone secretagogue receptor deficiency promotes lung cancer growth by affecting the Th17/Treg balance

Mechanisms Linking Vitamin D Deficiency to Impaired Metabolism: An Overview

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