Ablation of miRNA-22 protects against obesity-induced adipocyte senescence and ameliorates metabolic disorders in middle-aged mice

Lino, Caroline Antunes; Silva, Tábatha de Oliveira; Lunardon, Guilherme; Silva, Camila S Balbino; Lima, Vanessa Batista de Sousa; Huang, Zhan-Peng; Donato, José; Takano, Ana Paula Cremasco; Barreto-Chaves, Maria Luiza; Wang, Dazhi; Diniz, Gabriela Placoná

doi:10.1016/j.mad.2023.111775

Cited by 5 publications

(3 citation statements)

References 74 publications

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“…Another study reported that the knockdown of miR-133 is associated with cardiac hypertrophy [100]. Lino et al found that miR-22 was upregulated in middle-aged mice fed on HFD and its deletion attenuated weight gain and glucose imbalance and prevented white adipose tissue senescence [101]. Numerous miRNAs including miR-15 and let 7 family members are required for neonatal heart development and dysregulated expression of miR-195 (a miR-15 family member) is associated with heart abnormalities and arrest of the cell cycle at premature stage [102,103].…”

Section: Mirnas Modulated During Maternal Obesitymentioning

confidence: 99%

Dilemma of Epigenetic Changes Causing or Reducing Metabolic Disorders in Offsprings of Obese Mothers

Sharma,

Bhonde

2023

Horm Metab Res

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Maternal obesity is associated with fetal complications predisposing later to the development of metabolic syndrome during childhood and adult stages. High-fat diet seems to influence individuals and their subsequent generations in mediating weight gain, insulin resistance, obesity, high cholesterol, diabetes, and cardiovascular disorder. Research evidence strongly suggests that epigenetic alteration is the major contributor to the development of metabolic syndrome through DNA methylation, histone modifications, and microRNA expression. In this review, we have discussed the outcome of recent studies on the adverse and beneficial effects of nutrients and vitamins through epigenetics during pregnancy. We have further discussed about the miRNAs altered during maternal obesity. Identification of new epigenetic modifiers such as mesenchymal stem cells condition media (MSCs-CM)/exosomes for accelerating the reversal of epigenetic abnormalities for the development of new treatments is yet another aspect of the present review.

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Section: Mirnas Modulated During Maternal Obesitymentioning

confidence: 99%

Dilemma of Epigenetic Changes Causing or Reducing Metabolic Disorders in Offsprings of Obese Mothers

Sharma,

Bhonde

2023

Horm Metab Res

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“…MicroRNAs (miRNAs) are small, ~22 nucleotide-long single-stranded RNAs that posttranscriptionally decrease mRNA stability and/or translation efficiency through sequencespecific binding to the 3 ′ untranslated regions (3 ′ UTRs) of target mRNAs. MiRNAs play roles in most cellular activities, including multiple metabolic activities such as the regulation of glucose metabolism, obesity, and fatty acid oxidation by let-7, mir-22, and miR-33, respectively [13][14][15]. MiRNAs have also been implicated throughout the steps of glycolysis (Figure 1a) [16,17].…”

Section: Introductionmentioning

confidence: 99%

Unsaturated Fatty Acid Synthesis Is Associated with Worse Survival and Is Differentially Regulated by MYCN and Tumor Suppressor microRNAs in Neuroblastoma

Sheeter,

Garza,

Park

et al. 2024

Cancers

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MYCN amplification (MNA) and disruption of tumor suppressor microRNA (TSmiR) function are key drivers of poor outcomes in neuroblastoma (NB). While MYCN and TSmiRs regulate glucose metabolism, their role in de novo fatty acid synthesis (FAS) and unsaturated FAS (UFAS) remains poorly understood. Here, we show that FAS and UFAS (U/FAS) genes FASN, ELOVL6, SCD, FADS2, and FADS1 are upregulated in high-risk (HR) NB and that their expression is associated with lower overall survival. RNA-Seq analysis of human NB cell lines revealed parallel U/FAS gene expression patterns. Consistent with this, we found that NB-related TSmiRs were predicted to target these genes extensively. We further observed that both MYC and MYCN upregulated U/FAS pathway genes while suppressing TSmiR host gene expression, suggesting a possible U/FAS regulatory network between MYCN and TSmiRs in NB. NB cells are high in de novo synthesized omega 9 (ω9) unsaturated fatty acids and low in both ω6 and ω3, suggesting a means for NB to limit cell-autonomous immune stimulation and reactive oxygen species (ROS)-driven apoptosis from ω6 and ω3 unsaturated fatty acid derivatives, respectively. We propose a model in which MYCN and TSmiRs regulate U/FAS and play an important role in NB pathology, with implications for other MYC family-driven cancers.

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“…Additional NB-associated TSmiRs have been identified, including miR-1, miR-22, miR-24, miR-34, miR-101, miR-124, miR-140, miR-150, and miR-204 (33,(36)(37)(38)(39)(40)(41)(42)(43)(44). miRNAs play roles in most cellular activities, including multiple metabolic processes such as the regulation of glucose metabolism, obesity, and fatty acid oxidation by let-7, mir-22, and miR-33, respectively (45)(46)(47). Let-7 targets genes throughout the insulin-PI3K-mTOR pathway, including IGF1R, INSR, IRS2 and IGF2BP1.…”

Section: Introductionmentioning

confidence: 99%

Unsaturated fatty acid synthesis is associated with poor prognosis and differentially regulated byMYCNand tumor suppressor microRNAs in neuroblastoma

Sheeter

Garza

Park

et al. 2023

Preprint

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Genetic amplification ofMYCNand disruption of tumor suppressor (TS) microRNA (miRNA) function are central indicators of poor outcome in neuroblastoma (NB). While both MYC family activity and TS miRNAs (TSmiRs) have been broadly implicated in glucose metabolism, their role in unsaturated fatty acid synthesis (UFAS) is poorly understood. We show here that UFAS pathway genesFASN, ELOVL6, SCD, FADS2, andFADS1are overexpressed in human NB cell lines. Based on these data, we show that UFAS are associated with poor prognosis in high-risk NB patients, and that these genes contain extensive target sites for TSmiRsmiR-1, let-7, miR-22, miR-26, miR-34, miR-142, andmiR-204, all of which are known NB-associated TSmiR families. Several lines of evidence including KEGG pathway analysis indicate that increased MYC/N expression downregulates TSmiR which then attenuates inhibition of UFAS genes, causing increased synthesis of HUFA. Human NB cells grown under standard culture conditions are rich in ω9 Mead acid, and low in ω3 docosahexaenoic acid (DHA) and ω6 arachidonic acid (ARA) and adrenic acid (AdrA), consistent with dramatic upregulation of UFAS genes in NB. With this profile, immune stimulating ω6 fatty acid metabolites and reactive oxygen species (ROS)-driven apoptosis from ω3 fatty acids would both be low. Collectively, these observations establish a model in which the UFAS pathway plays a key role in NB patient outcomes, identifying novel roles forMYCNtranscriptional regulation of FAS and UFAS genes, as well as TSmiR post-transcriptional regulation of the UFAS pathway in NB, and MYC family driven cancers in general.

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Ablation of miRNA-22 protects against obesity-induced adipocyte senescence and ameliorates metabolic disorders in middle-aged mice

Cited by 5 publications

References 74 publications

Dilemma of Epigenetic Changes Causing or Reducing Metabolic Disorders in Offsprings of Obese Mothers

Dilemma of Epigenetic Changes Causing or Reducing Metabolic Disorders in Offsprings of Obese Mothers

Unsaturated Fatty Acid Synthesis Is Associated with Worse Survival and Is Differentially Regulated by MYCN and Tumor Suppressor microRNAs in Neuroblastoma

Unsaturated fatty acid synthesis is associated with poor prognosis and differentially regulated byMYCNand tumor suppressor microRNAs in neuroblastoma

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