ADIPOQ Gene Expression Research Articles

The contribution of adiponectin to diabetic retinopathy progression: Association with the AGEs-RAGE pathway

Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.

Identification of circulating apolipoprotein M as a new determinant of insulin sensitivity and relationship with adiponectin

BackgroundThe adiponectin is one of the rare adipokines down-regulated with obesity and protects against obesity-related disorders. Similarly, the apolipoprotein M (apoM) is expressed in adipocytes and its expression in adipose tissue is associated with metabolic health. We compared circulating apoM with adiponectin regarding their relationship with metabolic parameters and insulin sensitivity and examined their gene expression patterns in adipocytes and in the adipose tissue.MethodsCirculating apoM and adiponectin were examined in 169 men with overweight in a cross-sectional study, and 13 patients with obesity during a surgery-induced slimming program. Correlations with clinical parameters including the insulin resistance index (HOMA-IR) were analyzed. Multiple regression analyses were performed on HOMA-IR. The APOM and ADIPOQ gene expression were measured in the adipose tissue from 267 individuals with obesity and a human adipocyte cell line.ResultsParticipants with type 2 diabetes had lower circulating adiponectin and apoM, while apoM was higher in individuals with dyslipidemia. Similar to adiponectin, apoM showed negative associations with HOMA-IR and hs-CRP (r < −0.2), and positive correlations with HDL markers (HDL-C and apoA-I, r > 0.3). Unlike adiponectin, apoM was positively associated with LDL markers (LDL-C and apoB100, r < 0.20) and negatively correlated with insulin and age (r < −0.2). The apoM was the sole negative determinant of HOMA-IR in multiple regression models, while adiponectin not contributing significantly. After surgery, the change in HOMA-IR was negatively associated with the change in circulating apoM (r = −0.71), but not with the change in adiponectin. The APOM and ADIPOQ gene expression positively correlated in adipose tissue (r > 0.44) as well as in adipocytes (r > 0.81). In adipocytes, APOM was downregulated by inflammatory factors and upregulated by adiponectin.ConclusionsThe apoM rises as a new partner of adiponectin regarding insulin sensitivity. At the adipose tissue level, the adiponectin may be supported by apoM to promote a healthy adipose tissue.Trial registrationNCT01277068, registered 13 January 2011; NCT02332434, registered 5 January 2015; and NCT00390637, registered 20 October 2006.

Pathophysiology Crossroads: Examining the Role of Adiponectin (ADIPOQ) in the Intersection of Type II Diabetes and Dementia

Background: Type II Diabetes Mellitus (Type II DM) is intricately linked with an increased risk of cognitive impairment and dementia. The ADIPOQ gene encodes adiponectin, a hormone that plays a critical role in glucose regulation and fatty acid oxidation and may be implicated in the pathophysiology of both diabetes and dementia. Understanding the expression of ADIPOQ in diabetic patients with dementia could offer insights into the mechanisms at play and aid in the development of potential therapeutic targets. Objective: This study aims to analyze the expression of the ADIPOQ gene in diabetic patients diagnosed with dementia and to correlate these findings with cognitive impairment as assessed by Mini-Mental State Examination (MMSE) scores. Methods: We collected 5ml EDTA blood samples from 88 diabetic dementia patients and 12 healthy controls after obtaining written informed consent. The study adhered to the Declaration of Helsinki guidelines. Serum adiponectin levels were measured via Chemiluminescent immunoassay (CLIA), and genomic DNA was isolated for methylation-specific PCR and expression analysis. ADIPOQ gene expression was quantified using real-time PCR, and data were analyzed using SPSS version 25, employing descriptive and inferential statistics. Results: The diabetic dementia patient group demonstrated significantly lower adiponectin levels (5.62 ± 1.08 µg/mL) and MMSE scores (10.68 ± 4.56) compared to healthy controls (adiponectin: 15.68 ± 4.64 µg/mL, MMSE: 25.9 ± 3.12). Real-time PCR results indicated a relative fold decrease of 4.9 in ADIPOQ gene expression in the dementia cohort. Conclusion: The ADIPOQ gene expression is inversely associated with cognitive function in diabetic patients, highlighting its potential as a biomarker for early detection and targeted therapeutic interventions in dementia associated with diabetes.

An Insight into Wheat Germ Oil Nutrition, Identification of Its Bioactive Constituents and Computer-Aided Multidimensional Data Analysis of Its Potential Anti-Inflammatory Effect via Molecular Connections

Wheat germ oil (WGO) is the richest source of unexplored antioxidants and anti-inflammatory compounds. In this study, we identified the constituents of WGO by gas chromatography-mass spectrometry (GC-MS). The physicochemical and pharmacokinetic behaviors were evaluated for the top 12 constituents with the common target FABP4. Three fatty acids with significant anti-inflammatory activity were evaluated for their interaction with FABP4 by molecular docking. The molecular mechanisms involved in anti-inflammatory responses were analyzed by various in-silico analytical tools and multidimensional data analysis. WGO showed anti-inflammatory activities via FABP4 interacting physically with target genes (77.84%) and by co-expressing with 8.01% genes. Primary targets for inflammatory pathways were PPARα, PPARγ, LPL, LEP, and ADIPOQ, as depicted by gene network enrichment analysis. The key pathways implicated were the metabolism of lipids, PPAR signaling, cellular response to alcohol, oxygen and nitrogen pathway, inflammatory response pathway, and regulation of the inflammatory pathway. The common transcription factors implicated were HNF1, AP2α, CEBP, FOX, STATS, MYC, Zic, etc. In this study, we found that WGO possesses anti-inflammatory potential via FABP4 binding to PPARα, PPARγ, LPL, LEP, and ADIPOQ gene expression by regulatory transcription factors HNF, AP2α, and CEPB.

Study of Phenytoin Effect on the genes involved in glucose and lipid metabolism expression in liver: A mouse model study

Phenytoin as an anti-seizure medication, is useful for the prevention of tonic-clonic seizures and focal seizures. In this study we focused on the probable effects of Phenytoin drug on gene expression profile of liver related to lipid metabolism balance in mouse as a model. In this study, a group including 7 male mice of BALB/c were treated with phenytoin 3–5 mg/kg/day orally and a group including 7 male mice of BALB/c were took standard food. Liver tissue samples were isolated. Total RNA was extracted and cDNA was synthesized. Expression of Akt1 , Leptin, Adipoq and GLUT4 genes was measured using Real-time RT-PCR method. Results showed an increase about 15 and 3 fold changes in Akt1 and Adipoq gene expression respectively in treatment group compare to control mice. Also, we detected decreasing in Leptin and GLUT4 genes expression in the mice treated with phenytoin drug. Several studies indicated that phenytoin can promote hyperglycemia in human and animal. We proposed here that this effects may resulted from an interference between the phenytoin drug and gene expression profile in liver. Decreasing of leptin level here may be a result of glucose level elevation in blood that can induce a satiety situation result in decrease of leptin production. It may that Akt1 gene expression is increased to compensate the low level of GLUT4 protein. We concluded that phenytoin is a relatively high-risk antiepileptic drug for obesity and metabolic syndrome, but more studies are needed.

Gene expression of adipokines and adipokine receptors in the tumor microenvironment: associations of lower expression with more aggressive breast tumor features.

Limited epidemiologic data are available on the expression of adipokines leptin (LEP) and adiponectin (ADIPOQ) and adipokine receptors (LEPR, ADIPOR1, ADIPOR2) in the breast tumor microenvironment (TME). The associations of gene expression of these biomarkers with tumor clinicopathology are not well understood. NanoString multiplexed assays were used to assess the gene expression levels of LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 within tumor tissues among 162 Black and 55 White women with newly diagnosed breast cancer. Multivariate mixed effects models were used to estimate associations of gene expression with breast tumor clinicopathology (overall and separately among Blacks). Black race was associated with lower gene expression of LEPR (P = 0.002) and ADIPOR1 (P = 0.01). Lower LEP, LEPR, and ADIPOQ gene expression were associated with higher tumor grade (P = 0.0007, P < 0.0001, and P < 0.0001, respectively) and larger tumor size (P < 0.0001, P = 0.0005, and P < 0.0001, respectively). Lower ADIPOQ expression was associated with ER- status (P = 0.0005), and HER2-enriched (HER2-E; P = 0.0003) and triple-negative (TN; P = 0.002) subtypes. Lower ADIPOR2 expression was associated with Ki67+ status (P = 0.0002), ER- status (P < 0.0001), PR- status (P < 0.0001), and TN subtype (P = 0.0002). Associations of lower adipokine and adipokine receptor gene expression with ER-, HER2-E, and TN subtypes were confirmed using data from The Cancer Genome Atlas (P-values < 0.005). These findings suggest that lower expression of ADIPOQ, ADIPOR2, LEP, and LEPR in the breast TME might be indicators of more aggressive breast cancer phenotypes. Validation of these findings are warranted to elucidate the role of the adipokines and adipokine receptors in long-term breast cancer prognosis.

Deleted in breast cancer 1 plays a functional role in adipocyte differentiation.

Genetic deletion of Dbc1 in mice reduced adipose tissue senescence and inflammation while promoting an expansion of this tissue. Here, we aimed to investigate DBC1 mRNA and protein levels in human adipose tissue from subjects with a wide spectrum of fat mass (cohort 1; n = 105) and insulin resistance (cohort 2; n = 47); we also investigated the effects of DBC1 knockdown on 3T3-L1 adipocyte differentiation. DBC1 mRNA was relatively abundant in both visceral (VAT) and subcutaneous adipose tissue (SAT) (mainly in the adipocyte fraction), being decreased in adipose tissue from obese compared with lean subjects. In both VAT and SAT, DBC1 mRNA levels were negatively associated with BMI and positively associated with age and the expression of PPARγ, GLUT4, IRS1, lipogenic (FASN, ACACA), lipid droplet-associated genes (PLIN1, FSP27, ADRP, and TIP47), and lipolytic (ABDH5, AKAP, and PRKACA) genes but negatively associated with ADIPOQ in VAT. DBC1 mRNA and protein levels were increased in the early stages of adipocyte differentiation of human and 3T3-L1 adipocytes. Dbc1 knockdown (KD) with lentivirus led to enhanced adipocyte differentiation, increasing intracellular lipid accumulation and adipogenic gene expression. In conclusion, although DBC1 gene expression was reduced in adipose tissue from obese subjects, it was negatively associated with ADIPOQ gene expression in VAT, suggesting that DBC1 might promote visceral adipose tissue dysfunction. In vitro data supported the antiadipogenic effects of DBC1.

Role of adiponectin and proinflammatory gene expression in adipose tissue chronic inflammation in women with metabolic syndrome.

BackgroundThe purpose of this research was to study the gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), vascular endothelial growth factor A (VEGF-A) and adiponectin (AdipoQ) genes in the visceral (omental, mesenteric) and subcutaneous adipose tissue depots in metabolic syndrome (MS).We studied 23 women with MS, with a mean age of 50.7 ± 4.5 years and mean body mass index (BMI) of 45.6 ± 9.8 kg/m2. The control group included 10 women, with a mean age of 40.6 ± 8.7 years and normal BMI (22.3 ± 3.7 kg/m2). The gene expression levels in the omental (OAT), mesenteric (MAT) and subcutaneous (SAT) adipose tissues were assessed by quantitative real-time PCR.FindingsIncreased gene expression levels of IL-6 and TNF-α were detected in MAT in patients with MS, compared with the control group (p < 0.05 and p < 0.005, respectively). Significant positive correlations were observed between IL-6 mRNA expression levels in OAT and the content of CD14 + cells in the peripheral blood (r = 0.55, p < 0.05), as well as between NF-κB and VEGF-A mRNA levels in OAT (r = 0.43, p < 0.05) in patients with MS. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group (p < 0.05). In addition, there were inverse correlations between AdipoQ gene levels in MAT and serum CRP levels (r = −0.63, p < 0.05), as well as between AdipoQ gene levels in MAT and serum IL-6 levels (r = −0.46, p < 0.05).ConclusionThese data demonstrate that proinflammatory gene expression of MAT in women with MS was increased compared with the control group. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group.

Silencing of ADIPOQ Efficiently Suppresses Preadipocyte Differentiation in Porcine

Aims: Our study aims to characterize the functions of the ADIPOQ gene in the process of fat deposition of pigs, thereby providing a basis for the use of this gene as a molecular marker for pork quality. Methods: We used healthy Junmu1 piglets less than 7 days of age to establish an in vitro culture system for porcine preadipocytes. Chemically synthesized short hairpin RNAs (shRNA) were transfected into porcine preadipocytes to silence the expression of the ADIPOQ gene. We monitored preadipocyte differentiation and determined the levels of the adipocyte differentiation transcription factors lipoprotein lipase (LPL), peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte fatty acid binding protein (AP2) mRNAs to investigate the effects of ADIPOQ on the differentiation of porcine preadipocytes. Results: After transfection, the mRNA and protein levels of the ADIPOQ gene were significantly decreased (P < 0.01), the number of lipid droplets in the adipocytes was significantly reduced, the OD values reflecting the fat content were significantly decreased (P < 0.01), and the levels of LPL, PPARγ and AP2 were significantly reduced (P < 0.01). Conclusions: These results suggest that interference with ADIPOQ gene expression can inhibit the differentiation of porcine preadipocytes.

Genes implicated in insulin resistance are down-regulated in primary aldosteronism patients

Primary aldosteronism (PA) patients display an increased incidence of insulin resistance. Herein we demonstrate the decreased gene expression of lipid metabolism genes PCK1, PLIN, ADIPOQ and PPARG in the visceral adipose tissue (VAT) of PA patients compared to age-, sex- and BMI-matched controls. In VAT, the expression of PCK1, PLIN, ADIPOQ and PPARG was inversely correlated with aldosterone levels; furthermore, PLIN and ADIPOQ gene expression was correlated with potassium levels. Therefore, raised aldosterone and low potassium may contribute to the reduced expression of these genes in PA patients. Finally, incubation of primary cultures of human adipocytes with aldosterone resulted in a decrease in the expression of PCK1, PLIN and ADIPOQ and this effect was blocked by eplerenone. Therefore, the characteristic aldosterone excess of PA patients may mediate the down-regulation of PCK1, PLIN and ADIPOQ in VAT that in turn may contribute to the insulin resistance observed in PA patients.

Expression of the adiponectin gene (ADIPOQ) in the subcutaneous and visceral fatty tissues and the serum adiponectin level in children

The primary objective of the present work was to study specific features of adiponectin gene (ADIPOQ) expression in the subcutaneous and visceral fatty tissues along with the serum adiponectin level in children. The secondary objective was to elucidate the relationship between these variables and the basic anthropometric characteristics. The study included a total of 62 patients (31 boys and 31 girls at the age from 2.5 to 18 (median 13.6 (8.5-15.1) years] after they underwent planned surgical interventions. The expression of the adiponectin gene ADIPOQ was determined in paired samples of adipose tissue using the polymerase chain reaction in the real time; in addition, the serum adiponectin levels were measured. The expression of the adiponectin gene ADIPOQ was shown to be unrelated either to the age or to the sex of the children. Nor was there any significant difference between its expression in the subcutaneous and visceral tissues. The highest expression of mRNA encoding for adiponectin was recorded in the children at the Tanner stages 2-3 of sexual development. The ADIPOQ gene expression in the subcutaneous and visceral tissues of overweight children was 22% and 22.6% higher respectively than in the same tissues of normal weight children. Gene expression in the subcutaneous adipose tissue negatively correlated with the serum adiponectin level ( R = –0.38, p = 0.002), BMI SD (R = –0.35, p = 0.004 ), and the waist circumference (R = –0.36, p = 0.004). The results of the study suggest the necessity of further studies to clarify the pathophysiological role of adiponectin in the development of obesity and the related metabolic disturbances.