Serum‐ and glucocorticoid‐inducible kinase 1 promotes insulin resistance in adipocytes via degradation of insulin receptor substrate 1

Zhang, Min; Chen, Huan; Liu, Mengsi; Zhu, Keying; Hao, Yan; Zhu, Dalong; Li, Ping

doi:10.1002/dmrr.3451

Cited by 13 publications

(15 citation statements)

References 31 publications

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“…Inhibition of SGK1 expression by short hairpin RNA lentivirus led to reduced expression of adipogenic differentiation genes and increased expression of cell proliferation genes. The inhibition of insulin signalling by dexamethasone and oleic acid was reversed by lv-shSGK1 [41], whereas we observed that loss-of-function SGK1 led to down-regulation of proteins related to differentiation (PPARγ and C/EBPα) and no changes in proteins related to proliferation (CCDN2 and CDK2). This suggests that sh-SGK1 repressed bovine adipogenesis mainly by inhibiting adipocytes differentiation.…”

Section: Discussioncontrasting

confidence: 59%

SGK1 Affects the Phosphorylation of FOXO1/FOXO3 Promoting Bovine Fat Deposition via the PI3K/Akt Signaling Pathway

Lei

Wei

Tang

et al. 2022

Preprint

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Background: Improving the intramuscular fat content of beef not only could improve our living standard, but decrease the the risk of the disease from the aspect of human nutrition and diet. Serum/glucocorticoid-inducible kinase 1 (SGK1) is a critical kinase involved in regulating multiple metabolic processes. Results: In the present study we reveal the molecular mechanism by which SGK1 affects the phosphorylation of FOXO1 and FOXO3 thus regulating bovine fat deposition via the PI3K/Akt signaling pathway. SGK1 was characterized primarily in the bovine kidney, where it peaked at day 6 of preadipocyte differentiation. Overexpression of SGK1 in bovine preadipocytes promoted mRNA expression of adipose-specific genes, while cell cycle-related genes were repressed. Adipocyte differentiation-related proteins were not significantly changed, but proliferation-related proteins were markedly inhibited. Moreover, mRNA expression of adipose-specific genes were down-regulated while cell cycle-related genes were up-regulated in response to loss-of-function SGK1. The expression of adipose differentiation-related proteins were significantly inhibited but proliferation-related proteins were not significantly changed. Overexpression of SGK1 in bovine adipocytes significantly changed the gene expression enriched in the PI3K/Akt signaling pathways through RNA-seq. Subsequently, we found that overexpression of SGK1 increased phosphorylation of FOXO1/FOXO3 and reduced protein expression, whereas SGK1 deletion had opposite effects. Overall, we show that overexpression of SGK1 promotes adipogenesis mainly via inhibiting preadipocyte proliferation, whereas the loss-of-function of SGK1 represses adipogenesis mainly through inhibition of adipocyte differentiation. Mechanistically, SGK1 changes the phosphorylation of two key genes located downstream in the PI3K/Akt signaling pathway, FOXO1/FOXO3, thus promoting fat deposition in cattle. Conclusion: These data reveal that SGK1 is a positively regulatory during intramuscular adipogenesis of cattle, which expands the candidates regulating bovine adipogenesis and provides the security for human healthy from the aspect of high-quality beef.

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Section: Discussioncontrasting

confidence: 59%

SGK1 Affects the Phosphorylation of FOXO1/FOXO3 Promoting Bovine Fat Deposition via the PI3K/Akt Signaling Pathway

Lei

Wei

Tang

et al. 2022

Preprint

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“…The current knowledge was compiled in a gene regulation network of TH9 cells, which overlaps with T H 2 and T H 17 networks. The references for the network are as follows: [a:(Zhou et al, 2013), b:(Goswami et al, 2012), c:(Popp et al, 2017), d:(Chang et al, 2010), e:(Yee et al, 1998), f:(Mullen et al, 2011), g:(Mudter et al, 2011), h 50 , i:(Malik et al, 2017), j:(Takami et al, 2012), k:(Jash et al, 2012), l:(Kleinewietfeld et al, 2013), m:(Lu et al, 2010), n:(Seoane et al, 2004), o:(Harada et al, 2010), p:(Wu et al, 2020), q:(Takimoto et al, 2010), r:(Lee et al, 2019), (Jabeen et al, 2013), s:(Sahu et al, 2017), (Zhou et al, 2013)]. (B) CD4 + T cells were isolated from digested lungs of non-allergic and allergic WT and iCD4TGFBR2 mice and analyzed for IL-9 expression as well as T H 9 and T H 2 relevant transcription factors and signal molecules using quantitative RT-PCR.…”

Section: Resultsmentioning

confidence: 99%

TGF-β1 drives Th9 but not Treg cells upon allergen exposure

Musiol

Alessandrini

Jakwerth

et al. 2021

Preprint

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TGF-β1 is known to have a pro-inflammatory impact by inducing Th9 cells, while it also induces anti-inflammatory Treg cells (Tregs). In the context of allergic airway inflammation (AAI) its dual role can be of critical importance in influencing the outcome of the disease. Here we demonstrate that TGF-β acts in AAI by driving effector T cells into Th9 cells, while Tregs differentiate independently. Induction of experimental AAI and airway hyperreactivity in a mouse model with inducible genetic ablation of the TGFβ-receptor 2 (TGFBR2) on CD4+T cells significantly reduced the disease phenotype. Further, it blocked the induction of Th9 cell frequencies, but increased Treg cells. To translate these findings into a human clinically relevant context, Th9 and Treg cells were quantified both locally in induced sputum and systemically in blood of allergic rhinitis and asthma patients with or without allergen-specific immunotherapy (AIT). Natural allergen exposure induced local and systemic Th2, Th9 cell and reduced Tregs, while therapeutic allergen exposure by AIT suppressed Th2 and Th9 cell frequencies along with TGF-β and IL-9 secretion. Altogether, these findings support that neutralization of TGF-β represents a viable therapeutic option in allergy and asthma, not posing the risk of immune dysregulation by impacting Tregs.

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“…S2773; Selleck Chemicals). To overexpress SGK1 in MBSMCs, according to the literature, 25 , 26 the concentrations of Dex were 0, 1, 5, 10, 15 and 20 μmol/L, and culture medium containing 10% FBS was used. After 6 and 12 h, total cellular protein or supernatant was collected.…”

Section: Methodsmentioning

confidence: 99%

Serum/glucocorticoid‐regulated kinase 1‐targeted transient receptor potential oxalate subtype 1 regulates bladder smooth muscle cell proliferation due to bladder outlet obstruction in mice via activated T cell nuclear factor transcription factor 2

Yang

Chen

et al. 2022

IUBMB Life

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Bladder outlet obstruction (BOO) is a type of chronic disease that is mainly caused by benign prostatic hyperplasia. Previous studies discovered the involvements of both serum/glucocorticoid-regulated kinase 1 (SGK1) and activated T cell nuclear factor transcription factor 2 (NFAT2) in the proliferation of smooth muscle cells after BOO. However, the relationship between these two molecules is yet to be explored. Thus, this study explored the specific mechanism of the SGK1-NFAT2 signaling pathway in mouse BOO-mediated bladder smooth muscle cell proliferation in vivo and in vitro. In vivo experiments were performed by suturing 1/2 of the external urethra of female BALB/C mice to cause BOO for 2 weeks. In vitro, mouse bladder smooth muscle cells (MBSMCs) were treated with dexamethasone (Dex) or dexamethasone + SB705498 for 12 h and were transfected with SGK1 siRNA for 48 h. The expression and distribution of SGK1, transient receptor potential oxalate subtype 1 (TRPV1), NFAT2, and proliferating cell nuclear antigen (PCNA) were measured by Western blotting, polymerase chain reaction, and immunohistochemistry. The relationship between SGK1 and TRPV1 was analyzed by coimmunoprecipitation. The proliferation of MBSMCs was examined by 5-ethynyl-2 0 -deoxyuridine and cell counting kit 8 assays. Bladder weight, smooth muscle thickness, and collagen deposition in mice after 2 weeks of BOO were examined. Bladder weight, smooth muscle thickness, the

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Serum‐ and glucocorticoid‐inducible kinase 1 promotes insulin resistance in adipocytes via degradation of insulin receptor substrate 1

Cited by 13 publications

References 31 publications

SGK1 Affects the Phosphorylation of FOXO1/FOXO3 Promoting Bovine Fat Deposition via the PI3K/Akt Signaling Pathway

SGK1 Affects the Phosphorylation of FOXO1/FOXO3 Promoting Bovine Fat Deposition via the PI3K/Akt Signaling Pathway

TGF-β1 drives Th9 but not Treg cells upon allergen exposure

Serum/glucocorticoid‐regulated kinase 1‐targeted transient receptor potential oxalate subtype 1 regulates bladder smooth muscle cell proliferation due to bladder outlet obstruction in mice via activated T cell nuclear factor transcription factor 2

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