NPY stimulates cholesterol synthesis acutely by activating the SREBP2-HMGCR pathway through the Y1 and Y5 receptors in murine hepatocytes

Chen, Fu; Zhou, Yong; Yang, Keda; Shen, Mingyang; Wang, Yong

doi:10.1016/j.lfs.2020.118478

Cited by 27 publications

(22 citation statements)

References 46 publications

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“…CellChat analysis shows that the melanocortin signaling pathway acted as an autocrine pathway through the POMC – MC2R ligand receptor (Fig EV4B), as verified by Spatial transcriptome and immunofluorescence staining (Fig EV4C-D). NPY signaling pathway communication, especially between neurocytes and steroidogenic cells, is associated with cholesterol metabolism(Chen, Zhou et al, 2020) (Fig EV2G-H). The AGT signaling pathway is found between vascular myocytes and steroidogenic cells, suggesting a specific effect on sterol blood pressure(Lumbers & Pringle, 2014) and sterol insulin-resistant responsive cells(Pahlavani, Kalupahana et al, 2017) (Fig EV4E-F).…”

Section: Resultsmentioning

confidence: 99%

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads

Wang

Guo

et al. 2021

Preprint

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Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 GW via the 10× Genomics single-cell transcriptome techniques and reconstructed their location information by Spatial Transcriptome, conducted COOL-seq for the MC2R+ inner zone steroidogenic cells during the time window of sex differentiation (8-12GW). We found that relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple nonsteroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the time window of sex differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Furthermore, high SST+ expressions in the adrenal gland and testis amplify androgen synthesis in males. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.

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Section: Resultsmentioning

confidence: 99%

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads

Wang

Guo

et al. 2021

Preprint

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“…In the past few decades, NAFLD has become the most common chronic liver disease around the world (18,19). Although NAFLD is a benign disease, NASH (a progressive stage of NAFLD) is the second common cause for liver transplantation and increases hepatocarcinoma progression (2).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Key Genes and Pathways Involved in Nonalcoholic Steatohepatitis Improvement After Roux-en-Y Gastric Bypass Surgery

Zhou

et al. 2021

Front. Endocrinol.

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BackgroundAs the incidence of nonalcoholic fatty liver disease (NAFLD) increases globally, nonalcoholic steatohepatitis (NASH) has become the second common cause of liver transplantation for liver diseases. Recent evidence shows that Roux-en-Y gastric bypass (RYGB) surgery obviously alleviates NASH. However, the mechanism underlying RYGB induced NASH improvement is still elusive.MethodsWe obtained datasets, including hepatic gene expression data and histologic NASH status, at baseline and 1 year after RYGB surgery. Differentially expressed genes (DEGs) were identified comparing gene expression before and after RYGB surgery in each dataset. Common DEGs were obtained between both datasets and further subjected to functional and pathway enrichment analysis. Protein–protein interaction (PPI) network was constructed, and key modules and hub genes were also identified.ResultsIn the present study, GSE106737 and GSE83452 datasets were included. One hundred thirty common DEGs (29 up-regulated and 101 down-regulated) were identified between GSE106737 and GSE83452 datasets. KEGG analysis showed that mineral absorption, IL-17 signaling pathway, osteoclast differentiation, and TNF signaling pathway were significantly enriched. Based on the PPI network, IGF1, JUN, FOS, LDLR, TYROBP, DUSP1, CXCR4, ATF3, CXCL2, EGR1, SAA1, CTSS, and PPARA were identified as hub genes, and three functional modules were also extracted.ConclusionThis study identifies the global gene expression change in the liver of NASH patients before and after RYGB surgery in a bioinformatic method. Our findings will contribute to the understanding of molecular biological changes underlying NASH improvement after RYGB surgery.

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“…In the case of obese NAFLD patients, this polymorphism site was connected with a lower percentage of steatohepatitis and lobular inflammation [ 132 ]. The molecular mechanism of NPY activity relies on the up-regulation of the SREBP2/HMGCR pathway, where SREBP2 is a crucial transcription factor, regulating cholesterol homeostasis, and HMGCR is the rate-limiting enzyme in cholesterol synthesis [ 182 ].…”

Section: Genetic Determinants Of the Nafld Pathogenesismentioning

confidence: 99%

Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk

Dabravolski

Bezsonov

Baig

et al. 2021

IJMS

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NAFLD (non-alcoholic fatty liver disease) is a widespread liver disease that is often linked with other life-threatening ailments (metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, atherosclerosis, obesity, and others) and canprogress to more severe forms, such as NASH (non-alcoholic steatohepatitis), cirrhosis, and HCC (hepatocellular carcinoma). In this review, we summarized and analyzed data about single nucleotide polymorphism sites, identified in genes related to NAFLD development and progression. Additionally, the causative role of mitochondrial mutations and mitophagy malfunctions in NAFLD is discussed. The role of mitochondria-related metabolites of the urea cycle as a new non-invasive NAFLD biomarker is discussed. While mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) canbe used as effective diagnostic markers and target for treatments, age and ethnic specificity should be taken into account.

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NPY stimulates cholesterol synthesis acutely by activating the SREBP2-HMGCR pathway through the Y1 and Y5 receptors in murine hepatocytes

Cited by 27 publications

References 46 publications

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads

Integrated Analysis of Key Genes and Pathways Involved in Nonalcoholic Steatohepatitis Improvement After Roux-en-Y Gastric Bypass Surgery

Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk

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