A network-based approach to identify protein kinases critical for regulating srebf1 in lipid deposition causing obesity

Sun, Shouxiang; Cao, Xiaojuan; Castro, L. Filipe C.; Monroig, Óscar; Gao, Jian

doi:10.1007/s10142-021-00798-5

Cited by 12 publications

(12 citation statements)

References 43 publications

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“…A study proved that SREBP1 played a vital role in the regulation of LEP and could positively regulate the transcription of LEP 35 . As an adipogenic transcription factor, SREBP1 has been shown to play a critical role in regulating adipogenesis and inducing tumorigenesis 23,24,36 . Our study found that SREBP1 knockdown would obviously inhibit LEP secretion in adipocytes and then suppress the PD‐L1 expression of tumor cells in a co‐culture system.…”

Section: Discussionmentioning

confidence: 52%

“…35 As an adipogenic transcription factor, SREBP1 has been shown to play a critical role in regulating adipogenesis and inducing tumorigenesis. 23,24,36 Our study found that SREBP1…”

Section: Discussionmentioning

confidence: 62%

“…SREBF1, also known as SREBP1, is an adipogenic transcription factor 23 . It is widely reported that SREBP1 has the function of regulating lipid metabolism in the tumor microenvironment and of promoting cancer progression 24–26 .…”

Section: Resultsmentioning

confidence: 99%

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Baicalein enhances immune response in TNBC by inhibiting leptin expression of adipocytes

Liu,

Li,

et al. 2023

Cancer Science

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Triple‐negative breast cancer (TNBC) is a special pathological type of breast cancer (BC) with poor prognosis. Obesity is shown to be involved in TNBC tumor progression. The interaction between obesity and BC has generated great attention in recent years, however, the mechanism is still unclear. Here, we showed that leptin secreted by adipocytes upregulated PD‐L1 expression in TNBC through the p‐STAT3 signaling pathway and that baicalein inhibited PD‐L1 expression in tumor microenvironment by suppressing leptin transcription of adipocytes. Collectively, our findings suggest that leptin may be the key factor participating in obesity‐related tumor progression and that baicalein can break through the dilemma to boost the anti‐tumor immune response.

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Section: Discussionmentioning

confidence: 52%

“…35 As an adipogenic transcription factor, SREBP1 has been shown to play a critical role in regulating adipogenesis and inducing tumorigenesis. 23,24,36 Our study found that SREBP1…”

Section: Discussionmentioning

confidence: 62%

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Baicalein enhances immune response in TNBC by inhibiting leptin expression of adipocytes

Liu,

Li,

et al. 2023

Cancer Science

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“…Mgst is abundant in the liver and is involved in the transport and detoxification of the exnobiotics, providing protection against lipid peroxidation ( Gertsch et al, 2007 ). Srebf is master regulator of lipid production and metabolism ( Brown and Goldstein, 1997 ; Li et al, 2018 ; Reichert et al, 2021 ; Sun et al, 2021 ). Srebf1 is involved in the regulation of the synthesis and metabolism of cholesterol, fatty acids, and triglycerides ( Han et al, 2015 ; Robinet et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammation aggravated the hepatotoxicity of triptolide by oxidative stress, lipid metabolism disorder, autophagy, and apoptosis in zebrafish

Zhang

Zhu

et al. 2022

Front. Pharmacol.

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Triptolide is a major compound isolated from the Tripterygium wilfordii Hook that is mainly used for the treatment of autoimmune disorders and inflammatory diseases. Though triptolide-induced hepatotoxicity has been widely reported, the hepatic effects when the patients are in an inflammatory state are not clear. In this study, we used low-dose Lipopolysaccharides (LPS) to disrupt the inflammation homeostasis in the liver of zebrafish and explored the hepatotoxicity of triptolide under an inflammatory state. Compared with the Triptolide group, LPS-Triptolide cotreatment exacerbate the liver injury with a remarkable decrease of liver size and liver-specific fluorescence intensity, accompanied by significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Liver cell damages were further demonstrated by histological staining and scanning electron microscopy observation. Lipid metabolism was severely impaired as indicated by delayed yolk sac absorption, accumulated triglycerides in the liver, and dysregulation of the related genes, such as ppar-α, cpt-1, mgst, srebf1/2, and fasn. Oxidative stress could be involved in the molecular mechanism as the Nrf2/keap1 antioxidant pathways were down-regulated when the zebrafish in an inflammatory state. Moreover, the expression of autophagy-related genes such as beclin, atg5, map1lc3b, and atg3 was also dysregulated. Finally, apoptosis was significantly induced in responses to LPS-Triptolide co-treatment. We speculate that triptolide could exacerbate the immune response and impair lipid metabolism, resulting in enhanced sensitivity of the zebrafish liver to triptolide-induced toxic effects through disruption of the antioxidant system and induction of apoptosis.

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“…The metabolic role of testosterone, including an increase in lipogenic capacity in the gills, and TG levels in the brain, has been reported in gilthead sea bream ( Sparus auratus ) ( Sangiao-Alvarellos et al, 2006 ). Various studies employing genome-edited zebrafish ( Danio rerio ) to target key genes related to the steroidogenesis pathway have advanced our understanding of the relationship between androgen signaling and lipid homeostasis, establishing zebrafish as a valuable teleost model for molecular investigations of nutrient metabolism ( Li et al, 2020 ; Sun et al, 2021 ; Yang et al, 2018 ). In zebrafish, cytochrome P450 17A1 (CYP17A1) is a critical steroidogenic enzyme essential for androgen production, while AR functions as a nuclear receptor that mediates androgen action through specific ligand binding.…”

Section: Introductionmentioning

confidence: 99%

Androgen signaling inhibits <i>de novo</i> lipogenesis to alleviate lipid deposition in zebrafish

Jia,

Chen,

Shu

et al. 2024

Zoological Research

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Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1 -/- zebrafish ( Danio rerio ) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1 -/- fish compared to cyp17a1 +/+ male fish, including stearoyl-CoA desaturase ( scd ) and fatty acid synthase ( fasn ). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1 +/+ male fish but not in cyp17a1 -/- fish. Both androgen receptor ( ar )-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca ), fasn , and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1 -/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

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A network-based approach to identify protein kinases critical for regulating srebf1 in lipid deposition causing obesity

Cited by 12 publications

References 43 publications

Baicalein enhances immune response in TNBC by inhibiting leptin expression of adipocytes

Baicalein enhances immune response in TNBC by inhibiting leptin expression of adipocytes

Inflammation aggravated the hepatotoxicity of triptolide by oxidative stress, lipid metabolism disorder, autophagy, and apoptosis in zebrafish

Androgen signaling inhibits <i>de novo</i> lipogenesis to alleviate lipid deposition in zebrafish

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