IL-10/STAT3 is reduced in childhood obesity with hypertriglyceridemia and is related to triglyceride level in diet-induced obese rats

Liu, Yuesheng; Xu, Dong; Chen, Yin; Wang, Sisi; Wang, Min; Xiao, Yanfeng

doi:10.1186/s12902-018-0265-z

Cited by 38 publications

(31 citation statements)

References 40 publications

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“…This CpG site has recently been characterized as an LEP interaction region (chr7: 127,854,840-127,881,330). Also based on ENCODE data, cg15758240 is in the vicinity of a number of transcription factor binding sites, including YY1 (−99 bp), CEBPB (−144 bp), USF1 (−164 bp), STAT3 (−184 bp), and GATA2 (−204 bp), which has been previously linked to obesity [36][37][38][39][40], suggesting that cg15758240 is located within a genomic region relevant for both fat accretion and transcriptional regulation activity. Hence, we herein add to the current evidence that the harmful effects of maternal hyperglycemia on offspring adiposity and obesity risk is likely to include epigenetic dysregulation of the leptin gene pathway.…”

Section: Discussionmentioning

confidence: 99%

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Gagné-Ouellet

Breton

Thibeault

et al. 2020

IJMS

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Changes in fetal DNA methylation (DNAm) of the leptin (LEP) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5′-C-phosphate-G-3′ (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother–child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia (p ≤ 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (β = −2.69, p = 0.05) and fat distribution (β = −0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (β = −0.01, p = 0.04) and neonatal leptinemia (β = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia (p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood.

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Section: Discussionmentioning

confidence: 99%

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Gagné-Ouellet

Breton

Thibeault

et al. 2020

IJMS

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“…Large scale genomic studies in recent years have furthered our understanding of lncRNAs as functional adipogenic regulators [ 69 ]. IL-10 , an anti-inflammatory cytokine is known to contribute to childhood obesity [ 70 , 71 ], and Liu et al found that IL-10 and the downstream JAK-STAT pathway were down-regulated in obese children with hypertriglyceridemia and in HFD obese rats [ 72 ]. This, indicated a protective effect of IL-10 on lipid metabolic disorders, especially hypertriglyceridemia.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification and characterization of long non-coding RNAs during postnatal development of rabbit adipose tissue

Wang

et al. 2018

Lipids Health Dis

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BackgroundThe rabbit is widely used as an important experimental model for biomedical research, and shows low adipose tissue deposition during growth. Long non-coding RNAs (lncRNAs) are associated with adipose growth, but little is known about the function of lncRNAs in the rabbit adipose tissue.MethodsDeep RNA-sequencing and comprehensive bioinformatics analyses were used to characterize the lncRNAs of rabbit visceral adipose tissue (VAT) at 35, 85 and 120 days after birth. Differentially expressed (DE) lncRNAs were identified at the three growth stages by DESeq. The cis and trans prediction ways predicted the target genes of the DE lncRNAs. To explore the function of lncRNAs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the candidate genes.ResultsA total of 991,157,544 clean reads were generated after RNA-Seq of the three growth stages, of which, 30,353 and 107 differentially expressed (DE) lncRNAs were identified. Compared to the protein-coding transcripts, the rabbit lncRNAs shared some characteristics such as shorter length and fewer exons. Cis and trans target gene prediction revealed, 43 and 64 DE lncRNAs respectively, corresponding to 72 and 20 protein-coding genes. GO enrichment and KEGG pathway analyses revealed that the candidate DE lncRNA target genes were involved in oxidative phosphorylation, glyoxylate and dicarboxylate metabolism, and other adipose growth-related pathways. Six DE lncRNAs were randomly selected and validated by q-PCR.ConclusionsThis study is the first to profile the potentially functional lncRNAs in the adipose tissue growth in rabbits, and contributes to our understanding of mammalian adipogenesis.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0915-1) contains supplementary material, which is available to authorized users.

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“…In this respect, while STAT3 mRNA expression in adipose tissue is positively correlated with IL-10 and adiponectin expression, it is negatively correlated with triglycerides levels. Therefore, IL-10/JAK-STAT3 pathway activity is decreased due to obesity-related hypertriglyceridemia (Liu et al 2018). PI3K/Akt contributes to hypoxic stressinduced TLR4 expression through the regulation of HIF-1 activation (Kim et al 2012).…”

Section: Uncoupled Respiration and Hypoxiamentioning

confidence: 99%

The effect of adipocyte–macrophage crosstalk in obesity-related breast cancer

Engin

Gönül

2019

Journal of Molecular Endocrinology

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Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid and tumor necrosis factor-α involve in a vicious cycle between adipocytes and macrophages aggravating inflammatory changes. Thereby, M1 macrophages form a characteristic ‘crown-like structure (CLS)’ around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity and aggressive behavior of breast cancer cells. Interlinked molecular mechanisms between adipocyte–macrophage–breast cancer cells in obesity involve seven consecutive processes: Excessive release of adipocyte- and macrophage-derived inflammatory cytokines, TSC1–TSC2 complex–mTOR crosstalk, insulin resistance, endoplasmic reticulum (ER) stress and excessive oxidative stress generation, uncoupled respiration and hypoxia, SIRT1 controversy, the increased levels of aromatase activity and estrogen production. Considering elevated risks of estrogen receptor (E2R)-positive postmenopausal breast cancer growth in obesity, adipocyte–macrophage crosstalk is important in the aforementioned issues. Increased mTORC1 signaling in obesity ensures the strong activation of oncogenic signaling in E2Rα-positive breast cancer cells. Since insulin and insulin-like growth factors have been identified as tumor promoters, hyperinsulinemia is an independent risk factor for poor prognosis in breast cancer despite peripheral insulin resistance. The unpredictable effects of adipocyte-derived leptin–estrogen–macrophage axis, and sirtuin 1 (SIRT1)–adipose-resident macrophage axis in obese postmenopausal patients with breast cancer are unresolved mechanistic gaps in the molecular links between the tumor growth and adipocytokines.

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IL-10/STAT3 is reduced in childhood obesity with hypertriglyceridemia and is related to triglyceride level in diet-induced obese rats

Cited by 38 publications

References 40 publications

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Genome-wide identification and characterization of long non-coding RNAs during postnatal development of rabbit adipose tissue

The effect of adipocyte–macrophage crosstalk in obesity-related breast cancer

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