TCDD-inducible poly (ADP-ribose) polymerase promotes adipogenesis of both brown and white preadipocytes

Liu, Lingchao; Huwatibieke, Bahetiyaer; Lü, Xiaoqing; Li, Dexin; Dong, Haiyan; Han, Jing; Zhang, Weizhen; Zhang, Yi; Li, Yin

doi:10.2478/jtim-2021-0032

Cited by 5 publications

(2 citation statements)

References 38 publications

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“…Thus, numerous excellent studies that identified BC molecular subtypes have shed new light on BC precision medicine (3)(4)(5). Previous studies have revealed that DDR are complex biological processes, and it is well known that DDR pathways involve in the onset, progression, and therapeutic response of many diseases (6,43). Besides, treatment strategies that target altered DDR function are gradually coming to fruition.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analyses unravel DNA damage repair-related clusters in breast cancer with experimental validation

Liu,

Deng,

Zhou

et al. 2023

Front. Immunol.

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BackgroundAs one of the most common malignancies worldwide, breast cancer (BC) exhibits high heterogeneity of molecular phenotypes. The evolving view regarding DNA damage repair (DDR) is that it is context-specific and heterogeneous, but its role in BC remains unclear.MethodsMulti-dimensional data of transcriptomics, genomics, and single-cell transcriptome profiling were obtained to characterize the DDR-related features of BC. We collected 276 DDR-related genes based on the Molecular Signature Database (MSigDB) database and previous studies. We acquired public datasets included the SCAN-B dataset (GEO: GSE96058), METABRIC database, and TCGA-BRCA database. Corresponding repositories such as transcriptomics, genomics, and clinical information were also downloaded. We selected scRNA-seq data from GEO: GSE176078, GSE114727, GSE161529, and GSE158724. Bulk RNA-seq data from GEO: GSE176078, GSE18728, GSE5462, GSE20181, and GSE130788 were extracted for independent analyses.ResultsThe DDR classification was constructed in the SCAN-B dataset (GEO: GSE96058) and METABRIC database, Among BC patients, there were two clusters with distinct clinical and molecular characteristics: the DDR-suppressed cluster and the DDR-active cluster. A superior survival rate is found for tumors in the DDR-suppressed cluster, while those with the DDR-activated cluster tend to have inferior prognoses and clinically aggressive behavior. The DDR classification was validated in the TCGA-BRCA cohort and shown similar results. We also found that two clusters have different pathway activities at the genomic level. Based on the intersection of the different expressed genes among these cohorts, we found that PRAME might play a vital role in DDR. The DDR classification was then enabled by establishing a DDR score, which was verified through multilayer cohort analysis. Furthermore, our results revealed that malignant cells contributed more to the DDR score at the single-cell level than nonmalignant cells. Particularly, immune cells with immunosuppressive properties (such as FOXP3+ CD4+ T cells) displayed higher DDR scores among those with distinguishable characteristics.ConclusionCollectively, this study performs general analyses of DDR heterogeneity in BC and provides insight into the understanding of individualized molecular and clinicopathological mechanisms underlying unique DDR profiles.

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Section: Discussionmentioning

confidence: 99%

Multi-omics analyses unravel DNA damage repair-related clusters in breast cancer with experimental validation

Liu,

Deng,

Zhou

et al. 2023

Front. Immunol.

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“…[ 7 , 12 ] Lipidomics is a useful method of studying lipid metabolism under physiological and pathological conditions. [ 13 , 14 ] But to date, studies of the effects of exercise on lipid metabolism have mainly focused on the effects of acute or high-intensity exercise in adults or in individuals with specific diseases [ 7 , 9 , 11 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ] . Nieman et al .…”

Section: Introductionmentioning

confidence: 99%

Moderate-intensity continuous training has time-specific effects on the lipid metabolism of adolescents

Zhang

Liu

Cui

et al. 2023

Journal of Translational Internal Medicine

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Background and Objectives Moderate-intensity continuous training (MICT) is used to observe lipidomic effects in adults. However, the efects of MICT on lipid metabolism in adolescents remain unclear. Therefore, we aimed to longitudinally characterize the lipid profile in adolescents during different periods of 6-week MICT. Methods Fifteen adolescents undertook bicycle training at 65% of maximal oxygen consumption. Plasma samples were collected at four time points (T0, T1, T2, and T3). Targeted lipidomics was assessed by ultra-performance liquid chromatography–tandem mass spectrometry to characterize the plasma lipid profiles of the participants to identify the lipids present at differing concentrations and changes in lipid species with time. Results MICT afected the plasma lipid profiles of the adolescents. The concentrations of diglycerides, phosphatidylinositol, lysophosphatidic acid, lysophosphatidylcholine, and lysophosphatidylethanolamine were increased at T1, decreased at T2, and increased again at T3. Fatty acids (FAs) showed an opposite trend. Ether-linked alkylphosphatidylcholine and triglycerides were significantly increased and remained high. Sphingolipid concentrations initially decreased and then remained low. Therefore, a single bout of exercise had substantial efects on lipid metabolism, but by T3, fewer lipid species were present at significantly diferent concentrations and the magnitudes of the remaining diferences were smaller than those at earlier times. Among all the changed lipids, only DG(14:1/18:1), HexCer(d18:1/22:1) and FA(22:0) showed no significant correlations with any other 51 lipids (P < 0.05). Glycerides and phospholipids showed positive correlations with each other (P < 0.05), but FAs were significantly negatively correlated with glycerides and phospholipids while positively with other FAs (P < 0.05). Pathway enrichment analysis showed that 50% of the metabolic pathways represented were related to lipid metabolism and lipid biosynthesis. Conclusion MICT increases ether-linked alkylphosphatidylcholine and triglyceride concentrations. Diglyceride, phosphatidylinositol, and lysophosphatidylcholine concentrations initially rise and then decrease 6 weeks after MICT, but FA concentrations show an opposite trend. These changes might correlate with lipid metabolism or biosynthesis pathways.

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KLF13 restrains Dll4‐muscular Notch2 axis to improve the muscle atrophy

Yang,

Xiong,

Yang

et al. 2024

J cachexia sarcopenia muscle

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BackgroundMuscle atrophy can cause muscle dysfunction and weakness. Krüppel‐like factor 13 (KLF13), a central regulator of cellular energy metabolism, is highly expressed in skeletal muscles and implicated in the pathogenesis of several diseases. This study investigated the role of KLF13 in muscle atrophy, which could be a novel therapeutic target.MethodsThe effects of gene knockdown and pharmacological targeting of KLF13 on skeletal muscle atrophy were investigated using cell‐based and animal models. Clofoctol, an antibiotic and KLF13 agonist, was also investigated as a candidate for repurposing. The mechanisms related to skeletal muscle atrophy were assessed by measuring the expression levels and activation statuses of key regulatory pathways and validated using gene knockdown and RNA sequencing.ResultsIn a dexamethasone‐induced muscle atrophy mouse model, the KLF13 knockout group had decreased muscle strength (N) (1.77 ± 0.10 vs. 1.48 ± 0.16, P < 0.01), muscle weight (%) [gastrocnemius (Gas): 76.0 ± 5.69 vs. 60.7 ± 7.23, P < 0.001; tibialis anterior (TA): 75.8 ± 6.21 vs. 67.5 ± 5.01, P < 0.05], and exhaustive running distance (m) (495.5 ± 64.8 vs. 315.5 ± 60.9, P < 0.05) compared with the control group. KLF13 overexpression preserved muscle mass (Gas: 100 ± 6.38 vs. 120 ± 14.4, P < 0.01) and the exhaustive running distance (423.8 ± 59.04 vs. 530.2 ± 77.45, P < 0.05) in an in vivo diabetes‐induced skeletal muscle atrophy model. Clofoctol treatment protected against dexamethasone‐induced muscle atrophy. Myotubes treated with dexamethasone, an atrophy‐inducing glucocorticoid, were aggravated by KLF13 knockout, but anti‐atrophic effects were achieved by inducing KLF13 overexpression. We performed a transcriptome analysis and luciferase reporter assays to further explore this mechanism, finding that delta‐like 4 (Dll4) was a novel target gene of KLF13. The KLF13 transcript repressed Dll4, inhibiting the Dll4‐Notch2 axis and preventing muscle atrophy. Dexamethasone inhibited KLF13 expression by inhibiting myogenic differentiation 1 (i.e., MYOD1)‐mediated KLF13 transcriptional activation and promoting F‐Box and WD repeat domain containing 7 (i.e., FBXW7)‐mediated KLF13 ubiquitination.ConclusionsThis study sheds new light on the mechanisms underlying skeletal muscle atrophy and potential drug targets. KLF13 regulates muscle atrophy and is a potential therapeutic target. Clofoctol is an attractive compound for repurposing studies to treat skeletal muscle atrophy.

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TCDD-inducible poly (ADP-ribose) polymerase promotes adipogenesis of both brown and white preadipocytes

Cited by 5 publications

References 38 publications

Multi-omics analyses unravel DNA damage repair-related clusters in breast cancer with experimental validation

Multi-omics analyses unravel DNA damage repair-related clusters in breast cancer with experimental validation

Moderate-intensity continuous training has time-specific effects on the lipid metabolism of adolescents

KLF13 restrains Dll4‐muscular Notch2 axis to improve the muscle atrophy

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