Adipocyte最新文献

A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO). While young, regular chow diet-fed aKO mice showed increased insulin sensitivity, following prolonged (33 weeks) high-fat diet (HFD) exposure, aKO mice developed obesity and insulin resistance. Compared to controls, aKO mice showed less inflammatory adipokine profile despite the significant increase in adiposity. In brown adipose tissue, aKO mice on HFD had changes in CD8+ T cell populations indicating a lesser inflammatory pattern. Following HFD, both aKO and control littermates demonstrated decreased adipose tissue pro-inflammatory macrophages, and increased anti-inflammatory accumulation, without differences between the genotypes. Collectively, our observations indicate that selective deletion of ADAM10 in adipocytes results in a mitigated inflammatory response, leading to increased insulin sensitivity in young mice fed with regular diet. This state of insulin sensitivity, following prolonged HFD, facilitates energy storage resulting in increased fat accumulation which ultimately leads to the development of a phenotype of obesity and insulin resistance. In conclusion, the data indicate that ADAM10 has a modulatory effect of inflammation and whole-body energy metabolism.

Obesity is associated with a low-grade chronic inflammatory process characterized by higher circulating TNFα levels, thus contributing to insulin resistance. This study evaluated the effect of silybin, the main bioactive component of silymarin, which has anti-inflammatory properties, on TNFα levels and its impact on glucose uptake in the adipocyte cell line 3T3-L1 challenged with two different inflammatory stimuli, TNFα or lipopolysaccharide (LPS). Silybin's pre-treatment effect was evaluated in adipocytes pre-incubated with silybin (30 or 80 µM) before challenging with the inflammatory stimuli (TNFα or LPS). For the post-treatment effect, the adipocytes were first challenged with the inflammatory stimuli and then post-treated with silybin. After treatments, TNFα production, glucose uptake, and GLUT4 protein expression were determined. Both inflammatory stimuli increased TNFα secretion, diminished GLUT4 expression, and significantly decreased glucose uptake. Silybin 30 µM only reduced TNFα secretion after the LPS challenge. Silybin 80 µM as post-treatment or pre-treatment decreased TNFα levels, improving glucose uptake. However, glucose uptake enhancement induced by silybin did not depend on GLUT4 protein expression. These results show that silybin importantly reduced TNFα levels and upregulates glucose uptake, independently of GLUT4 protein expression.

Excessive deposit of epicardial adipose tissue (EAT) were recently shown to be positively correlated with cardiovascular disease (CVD). This study aims to investigate the thickness of EAT and its association with the components of metabolic syndrome among multi-ethnic Malaysians with and without acute coronary syndrome (ACS). A total of 213 patients were recruited, with the thickness of EAT were quantified non-invasively using standard two-dimensional echocardiography. EAT thickness among the Malaysian population was prompted by several demographic factors and medical comorbidities, particularly T2DM and dyslipidaemia. ACS patients have significantly thicker EAT compared to those without ACS (4.1 mm vs 3.7 mm, p = 0.035). Interestingly, among all the races, Chinese had the thickest EAT distribution (4.6 mm vs 3.8 mm), with age (p = 0.04 vs p < 0.001), and overall diastolic blood pressure (p = 0.028) was also found to be associated with EAT thickness. Further study is warranted to investigate its role as a cardiovascular risk marker among Malaysians with ACS.

Adipogenic differentiation and thermogenesis in brown adipose tissue (BAT) undergo dynamic processes, altering phenotypes and gene expressions. Proper reference genes in gene expression analysis are crucial to mitigate experimental variances and ensure PCR efficacy. Unreliable reference genes can lead to erroneous gene expression quantification, resulting in data misinterpretation. This study focused on identifying suitable reference genes for mouse brown adipocyte research, utilizing brown adipocytes from the Ucp1-luciferase ThermoMouse model. Comparative analysis of gene expression data under adipogenesis and thermogenesis conditions was conducted, validating 13 housekeeping genes through various algorithms, including DeltaCq, BestKeeper, geNorm, Normfinder, and RefFinder. Tbp and Rer1 emerged as optimal references for Ucp1 and Pparg expression in brown adipogenesis, while Tbp and Ubc were ideal for the expression analysis of these target genes in thermogenesis. Conversely, certain conventional references, including Actb, Tubb5, and Gapdh, proved unstable as reference genes under both conditions. These findings stress the critical consideration of reference gene selection in gene expression analysis within specific biological systems to ensure accurate conclusions.

Nicotinamide Adenine Dinucleotide (NAD) is an endogenous substance in redox reactions and regulates various functions in metabolism. NAD and its precursors are known for their anti-ageing and anti-obesity properties and are mainly active in the liver and muscle. Boosting NAD+ through supplementation with the precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), enhances insulin sensitivity and circadian rhythm in the liver, and improves mitochondrial function in the muscle. Recent evidence has revealed that the adipose tissue could be another direct target of NAD supplementation by attenuating inflammation and fat accumulation. Moreover, murine studies with genetically modified models demonstrated that nicotinamide phosphoribosyltransferase (NAMPT), a NAD regulatory enzyme that synthesizes NMN, played a critical role in lipogenesis and lipolysis in an adipocyte-specific manner. The tissue-specific effects of NAD+ metabolic pathways indicate a potential of the NAD precursors to control metabolic stress particularly via focusing on adipose tissue. Therefore, this narrative review raises an importance of NAD metabolism in white adipose tissue (WAT) through a variety of studies using different mouse models.

Obesity is a low-grade chronic inflammation induced by the pathological expansion of adipocytes which allows the development of obesity-associated metabolic diseases like type 2 diabetes mellitus (T2D) and non-alcoholic fatty liver disease (NAFLD). However, mechanisms regulating adipocyte inflammation remain poorly understood. Here, we observed that TRIM8 was upregulated in adipocyte inflammation and insulin resistance while DUSP14 was downregulated. TRIM8 deficiency and DUSP14 over-expression decreased the level of inflammatory cytokines, increased glucose uptake content, and improved insulin signalling transduction compared to LPS treatment alone. Conversely, silencing DUSP14 increased the expression of inflammatory cytokines. It decreased the glucose uptake content and the phosphorylation level of proteins involved in insulin signalling, further impairing insulin signalling and aggravating insulin resistance. Furthermore, The decreased level of inflammatory cytokines, increased glucose uptake, and improved insulin signalling transduction caused by TRIM8 deficiency were reversed by down-regulated DUSP14. Collectively, our findings revealed that TRIM8 can regulate adipocyte inflammation and insulin resistance by regulating the MAPKs pathway which is dependent on DUSP14.

White adipose tissue (WAT) is a dynamic organ capable of remodelling in response to metabolic state. For example, in response to stimuli such as cold exposure, WAT can develop inducible brown adipocytes ('browning') capable of non-shivering thermogenesis, through concurrent changes to mitochondrial content and function. This is aided by increased neurite outgrowth and angiogenesis across the tissue, providing the needed neurovascular supply for uncoupling protein 1 activation. While several RNA-sequencing studies have been performed in WAT, including newer single cell and single nuclei studies, little work has been done to investigate changes to the adipose proteome, particularly during dynamic periods of tissue remodelling such as cold stimulation. Here, we conducted a comprehensive proteomic analysis of inguinal subcutaneous (sc) WAT during the initial 'browning' period of 24 or 72hrs of cold exposure in mice. We identified four significant pathways impacted by cold stimulation that are involved in tissue remodelling, which included mitochondrial function and metabolism, cytoskeletal remodelling, the immune response, and the nervous system. Taken together, we found that early changes in the proteome of WAT with cold stimulation predicted later structural and functional changes in the tissue that are important for tissue and whole-body remodelling to meet energetic and metabolic needs.

Diabetic nephropathy (DN) and obesity bring a huge burden to society. Obesity plays a crucial role in the progression of type 2 DN, but the pathophysiology remains unclear. Thus, we aimed the explore the association between type 2 DN and obesity using bioinformatics method. The gene expression profiles of type 2 DN (GSE96804) and obesity (GSE94752) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened with the thresholds defined as |log2FC| ≥1 and P<0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Subsequently, a protein-protein interaction network was constructed based on the STRING database. Hub genes were identified, and the co-expression network was constructed. Finally, the hub genes were verified in clinical samples of 24 patients by immunohistochemistry. A total of 17 common DEGs were identified. Finally, two overlapping hub genes were identified (CCL18, C1QC). C1QC has been verified in clinical specimens. Using bioinformatics methods, the present study analyzed the common DEGs and the potential pathogenic mechanisms involved in type 2 DN and obesity. C1QC was the hub gene. Further studies are needed to clarify the specific relationships among C1QC, type 2 DN and obesity.

Background: Obesity increases the risk of atrial fibrillation (AF). We hypothesize that 'obese' epicardial adipose tissue (EAT) is, regardless of comorbidities, associated with markers of AF vulnerability.

Methods: Patients >40y of age undergoing bariatric surgery and using <2 antihypertensive drugs and no insulin were prospectively included. Study investigations were conducted before and 1y after surgery. Heart rhythm and p-wave duration were measured through ECGs and 7-d-holters. EAT-volume and attenuation were determined on non-enhanced CT scans. Serum markers were quantified by ELISA.

Results: Thirty-seven patients underwent surgery (age: 52.1 ± 5.9y; 27 women; no AF). Increased p-wave duration correlated with higher BMI, larger EAT volumes, and lower EAT attenuations (p < 0.05). Post-surgery, p-wave duration decreased from 109 ± 11 to 102 ± 11ms. Concurrently, EAT volume decreased from 132 ± 49 to 87 ± 52ml, BMI from 43.2 ± 5.2 to 28.9 ± 4.6kg/m², and EAT attenuation increased from -76.1 ± 4.0 to -71.7 ± 4.4HU (p <0.001). Adiponectin increased from 8.7 ± 0.8 to 14.2 ± 1.0 μg/ml (p <0.001). However, decreased p-wave durations were not related to changed EAT characteristics, BMI or adiponectin.

Conclusion: In this explorative study, longer p-wave durations related to higher BMIs, larger EAT volume, and lower EAT attenuations. P-wave duration and EAT volume decreased, and EAT attenuation increased upon drastic weightloss. However, there was no relation between decreased p-wave duration and changed BMI or EAT characteristics.

In mammals, brown adipose tissue (BAT) and beige adipocytes in white adipose tissue (WAT) play pivotal roles in maintaining body temperature and energy metabolism. In mice, BAT quickly stimulates thermogenesis by activating brown adipocytes upon cold exposure. In the presence of chronic cold stimuli, beige adipocytes are recruited in inguinal WAT to support heat generation. Accumulated evidence has shown that thermogenic execution of brown and beige adipocytes is regulated in a fat depot-specific manner. Recently, we have demonstrated that ubiquitin ligase ring finger protein 20 (RNF20) regulates brown and beige adipocyte thermogenesis through fat-depot-specific modulation. In BAT, RNF20 regulates transcription factor GA-binding protein alpha (GABPα), whereas in inguinal WAT, RNF20 potentiates transcriptional activity of peroxisome proliferator-activated receptor-gamma (PPARγ) through the degradation of nuclear corepressor 1 (NCoR1). This study proposes the molecular mechanisms by which co-regulator(s) selectively and temporally control transcription factors to coordinate adipose thermogenesis in a fat-depot-specific manner. In this Commentary, we provide molecular features of brown and beige adipocyte thermogenesis and discuss the underlying mechanisms of distinct thermogenic processes in two fat depots.