Adipocyte最新文献

The objective of this study was to identify key secretory protein-encoding differentially expressed genes (SP-DEGs) in adipose tissue in female metabolic syndrome, thus detecting potential targets in treatment. We examined gene expression profiles in 8 women with metabolic syndrome and 7 healthy, normal body weight women. A total of 143 SP-DEGs were screened, including 83 upregulated genes and 60 downregulated genes. GO analyses of these SP-DEGs included proteolysis, angiogenesis, positive regulation of endothelial cell proliferation, immune response, protein processing, positive regulation of neuroblast proliferation, cell adhesion and ER to Golgi vesicle-mediated transport. KEGG pathway analysis of the SP-DEGs were involved in the TGF-beta signalling pathway, cytokine‒cytokine receptor interactions, the hippo signalling pathway, Malaria. Two modules were identified from the PPI network, namely, Module 1 (DNMT1, KDM1A, NCoR1, and E2F1) and Module 2 (IL-7 R, IL-12A, and CSF3). The gene DNMT1 was shared between the network modules and the WGCNA brown module. According to the single-gene GSEA results, DNMT1 was significantly positively correlated with histidine metabolism and phenylalanine metabolism. This study identified 7 key SP-DEGs in adipose tissue. DNMT1 was selected as the central gene in the development of metabolic syndrome and might be a potential therapeutic target.

Immune cell infiltration into adipose tissue (AT) is a key factor in type 2 diabetes (T2DM). However, research on the impact of fat distribution on immune cells and immune responses in women is still lacking. This study used enrichment, protein-protein interaction network, immune cell infiltration, and correlation analysis to compare the similarities and differences between the transcriptome data of visceral AT (VAT) and subcutprotein-proteinaneous AT (SAT) obtained from the omprehensive database of gene expression in women with non-T2DM and T2DM. DEGs with the same biological function in two types of ATs often exhibited different expression trends. SharedVAT-specific and SAT-specific hub genes were mainly associated with transcription factors, monocyte-macrophage markers, and chemokines, respectively. Immune cells affected by both AT types included monocytes, granulocytes, T and B lymphocytes, and NK cells. VAT affected more immune cells, mainly myeloid cells. Shared hub genes in VAT correlated positively with M1 macrophages, suggesting pro-inflammatory effects, while those in SAT correlated negatively with M1 macrophages and lymphocytes, suggesting anti-inflammatory effects. This study provides a theoretical basis for further understanding the correlation between AT and T2DM in women.

Obesity is a global health concern that promotes chronic low-grade inflammation, leading to insulin resistance, a key factor in many metabolic diseases. Angiotensin 1-7 (Ang 1-7), a component of the renin-angiotensin system (RAS), exhibits anti-inflammatory effects in obesity and related disorders, though its mechanisms remain unclear. In this study, we examined the effect of Ang 1-7 on inflammation of white adipose tissue (WAT) in dietary-induced obese mice. Monocyte chemoattractant protein-1 (MCP-1) produced by white adipocytes and tumour necrosis factor-α (TNF-α) produced by macrophages are pro-inflammatory cytokines and interact to form a pathogenic loop to exacerbate obesity-induced inflammation. We found that Ang 1-7 reduced MCP-1 and TNF-α gene expressions and the number of crown-like structures, which are histological hallmarks of the pro-inflammatory process, in visceral epididymal WAT (eWAT) and reduced circulating MCP-1 and TNF-α levels, accompanied by improvement in insulin resistance, in dietary-induced obese mice. Furthermore, Ang 1-7 reduced MCP-1 and TNF-α secretions in 3T3-L1 white adipocytes and RAW 264.7 macrophages, respectively, which are in vitro experimental models mimicking obesity condition. Our results suggest that Ang 1-7 directly acts on WAT to mitigate obesity-induced inflammation. Thus, this study provides novel insights into the underlying mechanism of anti-obesity effects of Ang 1-7.

Lipid droplets (LDs) are highly specialized energy storage organelles involved in the maintenance of lipid homoeostasis by regulating lipid flux within white adipose tissue (WAT). The physiological function of adipocytes and LDs can be compromised by mutations in several genes, leading to NEFA-induced lipotoxicity, which ultimately manifests as metabolic complications, predominantly in the form of dyslipidemia, ectopic fat accumulation, and insulin resistance. In this review, we delineate the effects of mutations and deficiencies in genes - CIDEC, PPARG, BSCL2, AGPAT2, PLIN1, LIPE, LMNA, CAV1, CEACAM1, and INSR - involved in lipid droplet metabolism and their associated pathophysiological impairments, highlighting their roles in the development of lipodystrophies and metabolic dysfunction.

microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.

Background: Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients.

Methods: This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis.

Results: 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76-9.71) vs. 9.10(8.67-9.54), p < 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072-1.793, p < 0.001) and hospital (OR range 1.068-1.445, p = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (p = 0.014, 0.016, and < 0.001, respectively).

Conclusion: TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.

Background: Neuregulin 4 (Nrg4) is a brown adipose tissue-derived adipokine that greatly affects systemic metabolism and improves metabolic derangements. Although abnormal circulating levels of Nrg4 are common in obesity, it remains elusive whether low or elevated levels of this batokine are associated with the onset of metabolic diseases.

Aim: To assess Nrg4 levels and its role as a feasible biomarker to predict the severity of obesity, gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD).

Methods: A search for relevant studies was performed systematically using prominent search engines, including PubMed, Google Scholar, and Embase, by following PRISMA guidelines.

Results: Ample clinical evidence reported low serum/plasma levels of Nrg4 in obesity and these were inversely proportional to the indices of metabolic syndrome, including body mass index, waist circumference, triglycerides, fasting plasma glucose, and homoeostatic model assessment for insulin resistance as well as high-sensitivity C-reactive protein. Low circulating Nrg4 levels may aid in the prediction of morbid obesity, and subsequent GDM, T2DM, NAFLD, and CVD.

Conclusion: Current clinical evidence emphasizes that the circulating levels of Nrg4 are decreased in morbid obesity, and it also highlights that Nrg4 May serve as a potential prognostic biomarker for obesity-related metabolic diseases.

Obesity is a highly prevalent disorder with complex aetiology. Therefore, studying its associated cellular and molecular pathways may be aided by analysing genetic tractable diseases. In this context, the study of ciliopathies such as Bardet-Biedl syndrome has highlighted the relevance of primary cilia in obesity, both in the central nervous system and peripheral tissues. Based on our previous in vitro results supporting the role of a novel Bbs4-cilia-Fstl1 axis in adipocyte differentiation, we evaluated the in vivo relevance of the zebrafish orthologous genes fstl1a and fstl1b in primary cilia and adipose tissue development. Using a combination of knockdowns and a new fstl1a mutant line, we show that fstl1a promotes primary cilia formation in early embryos and participates in adipose tissue formation in larvae. We also show that fstl1b partially compensates for the loss of fstl1a. Moreover, in high fat diet, fstl1a depletion affects the expression of differentiation and mature adipocyte markers. These results agree with our previous in vitro data and provide further support for the role of FSTL1 as a regulator of adipose tissue formation. Dissecting the exact biological role of proteins such as FSTL1 will likely contribute to understand obesity onset and presentation.

Background: Platinum is a commonly used drug for ovarian cancer (OvCa) treatment, but drug resistance limits its clinical application. This study intended to delineate the effects of adipocytes on platinum resistance in OvCa.

Methods: OvCa cells were maintained in the adipocyte-conditioned medium. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, separately. Proliferation and apoptosis-related protein expression were assayed by western blot. The IC₅₀ values of cisplatin and carboplatin were determined using CCK-8. IGF1 secretion and expression were assayed via ELISA and western blot, respectively. A xenograft model was established, and pathological changes were detected by H&E staining. Proliferation and apoptosis-associated protein expression was assessed via IHC.

Results: Adipocytes promoted the viability and repressed cell apoptosis in OvCa, as well as enhancing platinum resistance, while the addition of IGF-1 R inhibitor reversed the effects of adipocytes on proliferation, apoptosis, and drug resistance of OvCa cells. Treatment with different concentrations of Ojeok-san (OJS) inhibited the adipocyte-induced platinum resistance in OvCa cells by suppressing IGF1. The combined treatment of OJS and cisplatin significantly inhibited tumour growth in vivo with good mouse tolerance.

Conclusion: In summary, OJS inhibited OvCa proliferation and platinum resistance by suppressing adipocyte paracrine IGF1 secretion.

Obesity is a globally prevalent metabolic disorder characterized by an increased number of adipose cells and excessive fat in adipocytes. Herbal medicines, such as ginger, have shown potential in treating obesity by inhibiting adipogenesis and reducing adipocyte hypertrophy. Ginger contains bioactive compounds, particularly gingerols, which have demonstrated anti-adipogenic and/or lipolytic effects. However, research on the effects of 10-gingerol on adipose tissue remains limited. This study aimed to evaluate the effect of 10-gingerol on lipid content, lipolysis markers, and the expression of genes related to lipid metabolism in 3T3-L1 adipocytes. Three groups were analyzed: a negative control (preadipocytes), a positive control (mature adipocytes), and a group treated with 10-gingerol (10-G). Results showed that 10-G reduced lipid accumulation by 42.16% in mature adipocytes compared to the control, without affecting cell viability. Additionally, 10-G increased glycerol release and downregulated lipogenic genes such as Pparγ, Acaca, Fabp4, and Mtor, while upregulating genes related to fatty acid oxidation, including Cebpα, Cpt1a, Lipe, and Prkaa1. In conclusion, 10-gingerol reduces lipid content in mature adipocytes by downregulating lipogenesis, increasing lipolysis, and enhancing fatty acid oxidation.