scholarly journals MiR-144 regulates adipogenesis by mediating formation of C/EBPα-FoxO1 protein complex

2021 ◽  
Author(s):  
Weimin Lin ◽  
Xianyu Wen ◽  
Xuexin Li ◽  
Lei Chen ◽  
Wei Wei ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Complex Formation ◽  
Molecular Mechanism ◽  
Protein Complex ◽  
Crucial Role ◽  
Type Ii Diabetes ◽  
Basic Unit ◽  
Type Ii ◽  
Treatment Of Obesity ◽  
Competitive Endogenous Rna

Excessive adipogenesis caused obesity, which was a serious risk of health and led to a series of diseases, including type II diabetes (T2D) for example. Adipocyte as the basic unit of adipose tissue has emerged as one of significant target of the treatment of obesity-related metabolic syndromes by revealed its adipogenic molecular mechanism. MicroRNAs (miRNAs) have been demonstrated involving adipogenesis, and played a crucial role in the competitive endogenous RNA (ceRNA) effect. Besides that, C/EBPα as a crucial adipogenic regulator still lacked epigenetic explanation during pre-adipocyte adipogenesis. In this study, we first verified FoxO1 was one of the ceRNA of C/EBPα. They co-regulated adipogenesis through formed a protein complex that directly bound to its promoter to activate AdipoQ, and AdipoQ (Adiponectin) was a negative adipocytokines that suppressed adipogenesis, which played an important role in retaining adipogensis balance. Moreover, an adipose tissue specific enriched miRNA, miR-144 was the key regulator of the ceRNA effect between C/EBPα and FoxO1, which mediated the C/EBPα-FoxO1 complex formation, thus altered AdipoQ, furthermore regulated pre-adipocyte adipogenesis. This research will provide a new supplementary idea of the C/EBPα epigenetic role in pre-adipocyte adipogenesis.

scholarly journals Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Franck Phan ◽  
Samia Boussouar ◽  
Olivier Lucidarme ◽  
Mohamed Zarai ◽  
Joe-Elie Salem ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Intensive Care ◽  
Interleukin 6 ◽  
Type Ii Diabetes ◽  
Troponin T ◽  
Early Mortality ◽  
Diabetic Patients ◽  
Type Ii ◽  
Short Term ◽  
Increased Risk

Abstract Background COVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission. Methods Eighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined. Results Of the enrolled patients (median age 66 years [IQR: 59–74]), 73% male, median body mass index (BMI) 27 kg/m2 [IQR: 24–31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2, p < 0.0001) and ICU-R (respectively OR = 3.27, p = 0.01; OR = 4.86, p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p < 0.0001). Conclusions Cardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission, a fortiori associated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.

Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size

2005 ◽  
Vol 288 (1) ◽  
pp. E117-E124 ◽  
Author(s):  
Mayumi Takahashi ◽  
Yasutomi Kamei ◽  
Osamu Ezaki
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
Type Ii Diabetes ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Peroxisome Proliferator ◽  
Type Ii ◽  
Fatty Acid Binding ◽  
Enhanced Expression

Obesity is a common and serious metabolic disorder in the developed world that is occasionally accompanied by type II diabetes, atherosclerosis, hypertension, and hyperlipidemia. We have found that mesoderm-specific transcript (Mest)/paternally expressed gene 1 (Peg1) gene expression was markedly enhanced in white adipose tissue of mice with diet-induced and genetically caused obesity/diabetes but not with streptozotocin-induced diabetes, which does not cause obesity. Administration of pioglitazone, a drug for type II diabetes and activator of peroxisome proliferator-activated receptor (PPAR)γ, in obese db/ db mice reduced the enhanced expression of Mest mRNA in adipose tissue, concomitant with an increase in body weight and a decrease in the size of adipose cells. Ectopic expression of Mest in 3T3-L1 cells caused increased gene expression of adipose markers such as PPARγ, CCAAT/enhancer binding protein (C/EBP)α, and adipocyte fatty acid binding protein (aP)2. In transgenic mice overexpressing Mest in adipose tissue, enhanced expression of the adipose genes was observed. Moreover, adipocytes were markedly enlarged in the transgenic mice. Thus Mest appears to enlarge adipocytes and could be a novel marker of the size of adipocytes.

scholarly journals Microdialysis assessment of local adipose tissue lipolysis during β-adrenergic stimulation in upper-body-obese subjects with type II diabetes

1999 ◽  
Vol 97 (4) ◽  
pp. 421 ◽  
Author(s):  
Ellen E. BLAAK ◽  
Gerrit J. KEMERINK ◽  
Marie Therese W. PAKBIERS ◽  
Bruce H.R. WOLFFENBUTTEL ◽  
Guido A. HEIDENDAL ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Type Ii Diabetes ◽  
Upper Body ◽  
Type Ii ◽  
Adrenergic Stimulation ◽  
Obese Subjects ◽  
Adipose Tissue Lipolysis

Adipose-on-a-chip: a dynamic microphysiological in vitro model of the human adipose for immune-metabolic analysis in type II diabetes

Lab on a Chip ◽  
2019 ◽  
Vol 19 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Yunxiao Liu ◽  
Patthara Kongsuphol ◽  
Su Yin Chiam ◽  
Qing Xin Zhang ◽  
Sajay Bhuvanendran Nair Gourikutty ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Type Ii Diabetes ◽  
In Vitro Model ◽  
Low Grade ◽  
Type Ii ◽  
Metabolic Analysis ◽  
Vitro Model ◽  
Low Grade Inflammation

Infiltration of immune cells into adipose tissue is associated with chronic low-grade inflammation in obese individuals.

scholarly journals Genetic Determinants of Obesity Heterogeneity in Type II Diabetes

2020 ◽  
Author(s):  
Somayeh Alsadat Hosseini Khorami ◽  
Mohd Sokhini Abd Mutalib ◽  
Mohammad Feili Shiraz ◽  
Joseph Anthony Abdullah ◽  
Zulida Rejali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Molecular Mechanism ◽  
Type Ii Diabetes ◽  
Insulin Signalling ◽  
Diabetic Group ◽  
Akt Pathway ◽  
Type Ii ◽  
Fasting State ◽  
Significant Difference

Abstract Background: Although obesity is considered as the main cause of Type II diabetes (T2DM), non-obese individuals may still develop T2DM and obese individuals may not. Method: The mRNA expression of insulin signalling components (PI3K/AKT axis) from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism. Result: In present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics. Conclusion: The components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.

scholarly journals Potential biomarkers of abnormal osseointegration of implants in type II diabetes mellitus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lingxiao Wang ◽  
Zhenhua Gao ◽  
Changying Liu ◽  
Jun Li
Keyword(s):  
Diabetes Mellitus ◽  
Bone Metabolism ◽  
Molecular Mechanism ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Type Ii ◽  
Receptor Interactions ◽  
Potential Biomarkers

Abstract Background Type II diabetes mellitus (T2DM) is an important risk factor for osseointegration of implants. The aim of this study was to explore key genes of T2DM affecting bone metabolism through bioinformatic analysis of published RNA sequencing data, identify potential biomarkers, and provide a reference for finding the molecular mechanism of abnormal osseointegration caused by T2DM. Methods We identified differentially expressed mRNAs and miRNAs from the Gene Expression Omnibus database using the R package ‘limma’ and analysed the predicted target genes using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology analysis. At the same time, miRNA–mRNA interactions were explored using miRWalk 2.0. Results We constructed an miRNA-gene regulatory network and a protein–protein interaction network. The enrichment pathways of differentially expressed mRNAs included extracellular matrix receptor interactions, protein digestion and absorption, the PI3K-Akt signalling pathway, cytokine–cytokine receptor interactions, chemokine signalling pathways, and haematopoietic cell lineage functions. We analysed the expression of these differentially expressed mRNAs and miRNAs in T2DM rats and normal rats with bone implants and identified Smpd3, Itga10, and rno-mir-207 as possible key players in osseointegration in T2DM. Conclusion Smpd3, Itga10, and rno-mir-207 are possible biomarkers of osseointegration in T2DM. This study sheds light on the possible molecular mechanism of abnormal osseointegration caused by bone metabolism disorder in T2DM.

scholarly journals Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice

2018 ◽  
Vol 45 (3) ◽  
pp. 1023-1033 ◽  
Author(s):  
Weina Cao ◽  
Yatao Xu ◽  
Dan Luo ◽  
Muhammad Saeed ◽  
Chao Sun
Keyword(s):  
Transcription Factor ◽  
Adipose Tissue ◽  
Transcriptional Activation ◽  
Methylation Level ◽  
Type Ii Diabetes ◽  
Luciferase Assay ◽  
Type Ii ◽  
Underlying Mechanisms

Background/Aims: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms. Methods: Quantitative real-time PCR (qPCR) and western blot were performed to determine Hoxa5 expression in primary adipocytes and in adipose tissues from mice. Lipid accumulation was evaluated by bodipy staining. Dual luciferase assay was applied to explore the transcription factor of Hoxa5 and the transcriptional target gene modulated by Hoxa5. All measurements were performed at least for three times at least. Results: A significant reduction of Hoxa5 expression was observed in adipose tissue of High Fat Diet (HFD) induced obesity mice. We determined Hoxa5 increased adipocytes differentiation and mitochondrial biogenesis in adipocytes in vitro. CEBPβ was determined a transcription factor of Hoxa5 and inhibited methylation level of Hoxa5 by combining on the promoter of Hoxa5. Importantly, we found Fabp4, a known positive regulator of adipocytes differentiation, was transcriptional activation by Hoxa5. In addition, Hoxa5 promotes adipocytes differentiation by inhibiting PKA/HSL pathway. Conclusion: Our study demonstrated the promoting role of Hoxa5 in adipocytes differentiation and therefore bringing a new therapeutic mean to the treatment of obesity and type II diabetes.

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