Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes

Menteşe, Ahmet; Alver, Ahmet; Sümer, Ayşegül; Demir, Selim

doi:10.1007/s12079-015-0316-4

Cited by 4 publications

(3 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lp-PLA2 protein levels appeared to be induced at an even earlier time point than mRNA expression. This apparent disparity may have arisen because of the capacity of the adipocyte to influx and digest oxLDL and LDL-cholesterol, releasing fatty acid, cholesterol and Lp-PLA2 [ 39 ]. As such, Lp-PLA2 is transported into the adipocyte bound to apolipoprotein B on LDL-cholesterol, its primary carrier [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

et al. 2018

View full text Add to dashboard Cite

Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Methods Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/ m 2 , n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m 2 , n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/ m 2 , n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m 2 , n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes. Results Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDLcholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05).

show abstract

Section: Discussionmentioning

confidence: 99%

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

et al. 2018

View full text Add to dashboard Cite

show abstract

“…HHcy is also one of the major contributing factors in obesity. Excess Hcy suppresses preadipocyte differentiation (Mentese et al 2016) and lipolysis in primary adipocytes (Wang et al 2011). Decreased lipolysis in adipocytes results in reduced levels of FFA for energy expenditure and accumulation of triglycerides in adipose tissues.…”

Section: Homocysteine and Obesitymentioning

confidence: 99%

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407

Laha

Majumder

Singh

et al. 2018

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases peroxisome proliferator-activated receptor γ (PPARγ) levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals, which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu and Zn, but this role of Hcy has not been established in relationship with obesity. It has been known for a while that PPARγ dysregulation results in various metabolic disorders including glucose and lipid metabolism. Recently, zinc finger protein 407 (Zfp407) is reported to regulate PPARγ target gene expression without affecting PPARγ transcript and protein levels by synergistically working with PPARγ. However, the mechanism(s) of this synergy, as well as other factors contributing to or inhibiting this synergism, have not been proven. This review suggests that Hcy contributes to pyroptosis, changes gut microbiome, and alters PPARγ-dependent mechanism(s) via Zfp407-mediated upregulated adipogenesis and misbalanced fatty acid metabolism, which can predispose to obesity and, consequently, obesity-related metabolic disorders.

show abstract

“…We also found reports on pyroptosis and lipid metabolism. High homocysteine (HCY) is a risk factor for obesity, elevated serum cysteine levels have been found in obese patients [ 90 ], and high levels of HCY can cause pyroptosis in the presence and absence of LPS [ 90 ]. Researchers found that NLRP3-related inflammation was activated in the fat pads of leptin-deficient mice and high-fat diet-fed obese mice and that NLRP3-dependent caspase-1 activation in hypertrophic adipocytes may induce obesity and adipocyte death through pyroptosis [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a Prognostic Model Based on Pyroptosis-Related Genes in Pancreatic Adenocarcinoma

Peng

2022

Disease Markers

View full text Add to dashboard Cite

Background. The importance of pyroptosis in tumorigenesis and cancer progression is becoming increasingly apparent. However, the efficacy of using pyroptosis-related genes (PRGs) in predicting the prognosis of pancreatic adenocarcinoma (PAAD) patients is unknown. Methods. This investigation used two databases to obtain expression data for PAAD patients. Differentially expressed PRGs (DEPRGs) were identified between PAAD and control samples. Several bioinformatic approaches were used to analyze the biological functions of DEPRGs and to identify prognostic DERPGs. A miRNA-prognostic DEPRG-transcription factor (TF) regulatory network was created via the miRNet online tool. A risk score model was created after each patient’s risk score was calculated. The microenvironments of the low- and high-risk groups were assessed using xCell, the expression of immune checkpoints was determined, and gene set variation analysis (GSVA) was performed. Finally, the efficacy of certain potential drugs was predicted using the pRRophetic algorithm, and the results in the high- and low-risk groups were compared. Results. A total of 13 DEPRGs were identified between PAAD and control samples. Functional enrichment analysis showed that the DEPRGs had a close relationship with inflammation. In univariate and multivariate Cox regression analyses, GSDMC, IRF1, and PLCG1 were identified as prognostic biomarkers in PAAD. The results of the miRNA-prognostic DEPRG-TF regulatory network showed that GSDMC, IRF1, and PLCG1 were regulated by both specific and common miRNAs and TFs. Based on the risk score and other independent prognostic indicators, a nomogram with a good ability to predict the survival of PAAD patients was developed. By evaluating the tumor microenvironment, we observed that the immune and metabolic microenvironments of the two groups were substantially different. In addition, individuals in the low-risk group were more susceptible to axitinib and camptothecin, whereas lapatinib might be preferred for patients in the high-risk group. Conclusion. Our study revealed the prognostic value of PRGs in PAAD and created a reliable model for predicting the prognosis of PAAD patients. Our findings will benefit the prognostication and treatment of PAAD patients.

show abstract

Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes

Cited by 4 publications

References 30 publications

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407

Development of a Prognostic Model Based on Pyroptosis-Related Genes in Pancreatic Adenocarcinoma

Contact Info

Product

Resources

About