Vaspin attenuates steatosis-induced fibrosis via GRP78 receptor by targeting AMPK signaling pathway

Objective: This work aimed to investigate the molecular mechanisms underlying the efficacy of vemurafenib as a treatment for melanoma. Methods: The GSE52882 dataset, which includes A375 and A2058 melanoma cell lines treated with vemurafenib and dimethyl sulfoxide (DMSO), and clinical information associated with melanoma patients, were acquired from the Gene Expression Omnibus (GEO) database and University of California Santa Cruz (UCSC), respectively. Functional enrichment analysis, protein-protein interaction (PPI) network construction, sub-module analysis, and transcriptional regulation analysis were performed on overlapping differentially expressed genes (DEGs) identified in both cell lines. Finally, we performed a survival analysis based on the genes identified. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Conclusion: MMP2, CXCL8, PIK3R3, ITGB3, and LEF1 may play roles in the efficacy of vemurafenib treatment in melanoma; for example, MMP2 and PIK3R3 are likely associated with vemurafenib resistance. These findings will contribute to the development of novel therapies for melanoma.

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DNA methylation mediates the association between breastfeeding and early-life growth trajectories

Clinical Epigenetics ◽

10.1186/s13148-021-01209-z ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Laurent Briollais ◽

Denis Rustand ◽

Catherine Allard ◽

Yanyan Wu ◽

Jingxiong Xu ◽

...

Keyword(s):

Dna Methylation ◽

Signaling Pathway ◽

Exclusive Breastfeeding ◽

Child Growth ◽

Postnatal Period ◽

Overweight And Obesity ◽

Breastfeeding Duration ◽

Ampk Signaling ◽

Cpg Sites ◽

Genome Wide

Abstract Background The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth. Results Exclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth. At the genome-wide level, 13 CpG sites in girls (miR-21, SNAPC3, ATP6V0A1, DHX15/PPARGC1A, LINC00398/ALOX5AP, FAM238C, NATP/NAT2, CUX1, TRAPPC9, OSBPL1A, ZNF185, FAM84A, PDPK1) and 2 CpG sites in boys (IL16 and NREP), mediate the association between exclusive breastfeeding and longitudinal BMI. We found enrichment of CpG sites located within miRNAs and key pathways (AMPK signaling pathway, insulin signaling pathway, endocytosis). Overall DNA methylation variation corresponding to 3 to 5 months of exclusive breastfeeding was associated with slower BMI growth the first 6 years of life compared to no breastfeeding and in a dose–response manner with exclusive breastfeeding duration. Conclusions Our study confirmed the early postnatal period as a critical developmental period associated with substantial DNA methylation variations, which in turn could mitigate the development of overweight and obesity from infancy to early childhood. Since an accelerated growth during these developmental periods has been linked to the development of sustained obesity later in life, exclusive breastfeeding could have a major role in preventing the risks of overweight/obesity and children and adults through DNA methylation mechanisms occurring early in life.

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Omics multi-layers networks and identification of genes involved in fat storage and metabolism in poultry using interactomics approach

10.21203/rs.3.rs-30697/v1 ◽

2020 ◽

Author(s):

abolfazl bahrami ◽

Farzad Ghafouri ◽

Mostafa Sadeghi ◽

Seyed Reza Miraei-Ashtiani

Keyword(s):

Adipose Tissue ◽

Signaling Pathway ◽

High Throughput Screening ◽

Broiler Chickens ◽

Unsaturated Fatty Acids ◽

Holistic Approach ◽

High Rate ◽

Literature Mining ◽

Ampk Signaling ◽

Ppar Signaling

Abstract Background Fatty acid metabolism in animals has a major impact on production and disease resistance traits. According to the high rate of interactions between lipid metabolism and its regulating properties, a holistic approach is necessary. Methods To study multi-omics layers of adipose tissue and identification of genes involved in fat metabolism, storage and endocrine signaling pathways in two groups of broiler chickens with high and low abdominal fat, high-throughput screening (HTS) techniques were used. The Gene-miRNA interacting bipartite and metabolic-signaling networks were reconstructed using their interactions. Results In the analysis of microarray and RNA-Seq data, 1835 genes were detected by comparing the identified genes with significant expression differences. Then, by comparing, 34 genes and 19 miRNAs were detected as common and main nodes. The literature mining approach was used and 7 genes were identified and added to the common gene set. Module finding revealed three important and functional modules. The detected modules 1, 2, and 3 were involved in the PPAR signaling pathway, biosynthesis of unsaturated fatty acids, and Alzheimer's disease metabolic pathway, adipocytokine, insulin, PI3K-Akt, mTOR and AMPK signaling pathway. Conclusions This approach revealed a new insight for a better understanding of the biological processes associated with adipose tissue.

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Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

Endocrine Connections ◽

10.1530/ec-20-0466 ◽

2020 ◽

Author(s):

Zhiwei Zhang ◽

Hui Zhao ◽

Aixia Wang

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Body Weight ◽

Blood Glucose ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Signaling Pathway ◽

Hepatic Glycogen ◽

Ampk Signaling ◽

Tnf Α

Background: Gestational diabetes mellitus (GDM) has a high incidence rate among pregnant women. The objective of the study was to assess the effect of plant-derived oleuropein in attenuating inflammatory and oxidative stress of GDM. Methods: Oleuropein was administered to GDM mice at the doses of 5 or 10 mg/kg/day. Body weight, blood glucose, insulin and hepatic glycogen levels were recorded. To evaluate the effect of oleuropein in reducing oxidative stress, enzyme-linked immunosorbent assay (ELISA) was used to measure the hepatic oxidative stress markers. The inflammation levels of GDM mice were evaluated by measuring serum levels of IL-6 and TNF-α by ELISA, and mRNA levels of IL-1β, TNF-α and IL-6 by real-time PCR (RT-PCR). The AMP-activated protein kinase (AMPK) signaling pathway was assessed by Western blot. Gestational outcome was analyzed through comparing litter size and birth weight. Results: Oleuropein attenuated the elevated body weight of GDM mice, and efficiently reduced blood glucose, insulin and hepatic glycogen levels. Oxidative stress and inflammation were alleviated by oleuropein treatment. The AMPK signaling was activated by oleuropein in GDM mice. Gestational outcome was markedly improved by oleuropein treatment. Conclusions: Our study suggests that oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model. This effect is achieved by attenuating oxidative stress and inflammation, which is mediated by the activation of the AMPK signaling pathway.

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Betatrophin knockdown induces beiging and mitochondria biogenesis of white adipocytes

Journal of Endocrinology ◽

10.1530/joe-19-0447 ◽

2020 ◽

Vol 245 (1) ◽

pp. 93-100 ◽

Cited By ~ 1

Author(s):

Zhe-Zhen Liao ◽

Xiao-Yan Qi ◽

Ya-Di Wang ◽

Jiao-Yang Li ◽

Qian-Qian Gu ◽

...

Keyword(s):

Signaling Pathway ◽

Ampk Signaling ◽

White Adipocytes ◽

Beige Adipocytes ◽

Beige Fat ◽

Mitochondria Biogenesis ◽

Paracrine Actions ◽

White Fat

Remodeling of energy-storing white fat into energy-consuming beige fat has led to a promising new approach to alleviate adiposity. Several studies have shown adipokines can induce white adipose tissue (WAT) beiging through autocrine or paracrine actions. Betatrophin, a novel adipokine, has been linked to energy expenditure and lipolysis but not clearly clarified. Here, we using high-fat diet-induced obesity to determine how betatrophin modulate beiging and adiposity. We found that betatrophin-knockdown mice displayed less white fat mass and decreased plasma TG and NEFA levels. Consistently, inhibition of betatrophin leads to the phenotype change of adipocytes characterized by increased mitochondria contents, beige adipocytes and mitochondria biogenesis-specific markers both in vivo and in vitro. Of note, blocking AMP-activated protein kinase (AMPK) signaling pathway is able to abolish enhanced beige-like characteristics in betatrophin-knockdown adipocytes. Collectively, downregulation of betatrophin induces beiging in white adipocytes through activation of AMPK signaling pathway. These processes suggest betatrophin as a latent therapeutic target for obesity.

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