Human Folate Receptor-1 Gene Expression and Correlation with Physiological Leptin hormone in Obese and Non-obese Subjects

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

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Circulating cortisol-associated signature of glucocorticoid-related gene expression in subcutaneous fat of obese subjects

Obesity ◽

10.1002/oby.20073 ◽

2013 ◽

Vol 21 (5) ◽

pp. 960-967 ◽

Cited By ~ 7

Author(s):

Maria G. Pavlatou ◽

Kasey C. Vickers ◽

Sudhir Varma ◽

Rana Malek ◽

Maureen Sampson ◽

...

Keyword(s):

Gene Expression ◽

Subcutaneous Fat ◽

Related Gene ◽

Obese Subjects

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Caged siRNAs with single folic acid modification of antisense RNA for photomodulation of exogenous and endogenous gene expression in cells

Organic & Biomolecular Chemistry ◽

10.1039/c8ob01952e ◽

2018 ◽

Vol 16 (38) ◽

pp. 7029-7035 ◽

Cited By ~ 4

Author(s):

Lijia Yu ◽

Nannan Jing ◽

Zhenjun Yang ◽

Lihe Zhang ◽

Xinjing Tang

Keyword(s):

Gene Expression ◽

Folic Acid ◽

Complex Formation ◽

Antisense Rna ◽

Folate Receptor ◽

Acid Modification ◽

Endogenous Gene ◽

In Cells

Photoregulating gene expression using folic acid modified caged siRNA through complex formation of folic acid/folate receptor.

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Metallothionein Gene Expression in Human Adipose Tissue from Lean and Obese Subjects

Hormone and Metabolic Research ◽

10.1055/s-2002-33254 ◽

2002 ◽

Vol 34 (6) ◽

pp. 348-351 ◽

Cited By ~ 26

Author(s):

M.-S. Do ◽

S.-Y. Nam ◽

S.-E. Hong ◽

K. W. Kim ◽

J. S. Duncan ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Metallothionein Gene ◽

Obese Subjects

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Serum concentrations and expressions of serum amyloid A and leptin in adipose tissue are interrelated: the Genobin Study

Acta Endocrinologica ◽

10.1530/eje-07-0598 ◽

2008 ◽

Vol 158 (3) ◽

pp. 333-341 ◽

Cited By ~ 19

Author(s):

T Lappalainen ◽

M Kolehmainen ◽

U Schwab ◽

L Pulkkinen ◽

D E Laaksonen ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

Adipose Tissue ◽

Weight Reduction ◽

Serum Amyloid A ◽

Normal Weight ◽

Serum Amyloid ◽

Serum Concentrations ◽

Amyloid A ◽

Obese Subjects

ObjectiveSerum amyloid A (SAA) is a novel link between increased adipose tissue mass and low-grade inflammation in obesity. Little is known about the factors regulating its serum concentration and mRNA levels. We investigated the association between SAA and leptin in obese and normal weight subjects and analyzed the effect of weight reduction on serum SAA concentration and gene expression in adipose tissue of the obese subjects.MethodsSeventy-five obese subjects (60±7 years, body mass index (BMI) 32.9±2.8 kg/m2, mean±s.d.) with impaired fasting plasma glucose or impaired glucose tolerance and other features of metabolic syndrome, and 11 normal weight control subjects (48±9 years, BMI 23.7±1.9 kg/m2) were studied at the baseline. Twenty-eight obese subjects underwent a 12-week intensive weight reduction program followed by 5 months of weight maintenance. Blood samples and abdominal s.c. adipose tissue biopsies were taken at the baseline and after the follow-up. Gene expression was studied using real-time quantitative PCR.ResultsThe gene expressions in women and serum concentrations of leptin and SAA were interrelated independently of body fat mass in the obese subjects (r=0.54, P=0.001; r=0.24, P=0.039 respectively). In multiple linear regression analyses, leptin mRNA explained 38% of the variance in SAA mRNA (P=0.002) in the obese women. Weight loss of at least 5% increased SAA mRNA expression by 48 and 36% in men and women, but serum SAA concentrations did not change.ConclusionsThe association between SAA and leptin suggests an interaction between these two adipokines, which may have implications in inflammatory processes related to obesity and the metabolic syndrome.

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Differences in metabolic biomarkers in the blood and gene expression profiles of peripheral blood mononuclear cells among normal weight, mildly obese and moderately obese subjects

British Journal Of Nutrition ◽

10.1017/s0007114516002993 ◽

2016 ◽

Vol 116 (6) ◽

pp. 1022-1032 ◽

Cited By ~ 14

Author(s):

Un Ju Jung ◽

Yu Ri Seo ◽

Ri Ryu ◽

Myung-Sook Choi

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Peripheral Blood ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Hdl Cholesterol ◽

Normal Weight ◽

Peripheral Blood Mononuclear ◽

Obese Subjects ◽

Metabolic Biomarkers

AbstractWe compared metabolic biomarkers in the blood and peripheral blood mononuclear cell (PBMC) gene expression profiles among normal weight (BMI, 18·5–23 kg/m2), mildly obese (BMI, 25–27·5 kg/m2) and moderately obese Korean adult men (BMI, 27·5–30 kg/m2). High leptin, lipids (except LDL- and HDL-cholesterol) and apoB levels and low adiponectin and HDL-cholesterol levels were present in the plasma of both mildly and moderately obese subjects. Circulating levels of inflammatory cytokines and markers of insulin resistance, oxidative stress and liver damage were altered in moderately obese subjects but not in mildly obese subjects. PBMC transcriptome data showed enrichment of pathways involved in energy metabolism, insulin resistance, bone metabolism, cancer, inflammation and fibrosis in both mildly and moderately obese subjects. Signalling pathways involved in oxidative phosphorylation, TAG synthesis, carbohydrate metabolism and insulin production; mammalian target of rapamycin, forkhead box O, ras-proximate-1, RAS and transforming growth factor-β signalling; as well as extracellular matrix–receptor interaction were enriched only in moderately obese subjects, indicating that changes in PBMC gene expression profiles, according to metabolic disturbances, were associated with the development and/or aggravation of obesity. In particular, fourteen and fifteen genes differentially expressed only in mildly obese subjects and in both mildly and moderately obese subjects, respectively, could be used as early or stable biomarkers for diagnosing and treating obesity-associated metabolic disturbance. We characterised BMI-associated metabolic and molecular biomarkers in the blood and provided clues about potential blood-based targets for preventing or treating obesity-related complications.

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Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00574.2009 ◽

2010 ◽

Vol 298 (4) ◽

pp. E824-E831 ◽

Cited By ~ 123

Author(s):

Tore Christiansen ◽

Søren K. Paulsen ◽

Jens M. Bruun ◽

Steen B. Pedersen ◽

Bjørn Richelsen

Keyword(s):

Gene Expression ◽

Weight Loss ◽

Exercise Training ◽

Inflammatory Markers ◽

Very Low Energy Diet ◽

Beneficial Effects ◽

Weight Losses ◽

Obese Subjects ◽

Randomized Intervention Study ◽

Circulating Inflammatory Markers

The purpose of this study was to investigate the effect of exercise training and diet-induced weight loss alone or in combination on inflammatory markers in circulation, in adipose tissue (AT) and in skeletal muscle (SM) in obese subjects. Seventy-nine obese subjects were randomized into a 12-wk intervention: 1) exercise only (EXO), 2) diet-induced weight loss using a very low energy diet (DIO), and 3) exercise and diet-induced weight-loss combined (DEX). Blood samples (metabolic and inflammatory markers) and AT and SM biopsies (mRNA expression) were collected at baseline and after 12 wk. In the EXO group the weight loss was 3.5 kg and in the DIO and DEX groups it was 12 kg in both. V̇o2max was increased by 14–18% in the EXO and DEX groups with no changes in the DIO group. In the DIO and DEX groups, circulating levels of MCP-1, MIP-1α, IL-15, and IL-18 were decreased, and adiponectin was increased ( P < 0.05 for all). In the EXO group, MCP-1 was decreased with 10% ( P = 0.06). By combining the weight loss in all three groups, we found a correlation between the degree of weight loss and improvement in several of the inflammatory markers ( P < 0.05). In AT biopsies, subjects in the DIO and DEX groups achieved a general beneficial but nonsignificant effect on the gene expression of inflammatory markers. In the EXO group, no changes in AT adipokine mRNA were found except for an increment of adiponectin ( P < 0.05). In SM, the only observed change was that the gene expression of IL-6 was increased in all three groups ( P < 0.05). In conclusion, rather large weight losses (>5–7%) were found to have beneficial effects on circulating inflammatory markers in these obese subjects. Aerobic exercise for 12 wk, which increased V̇o2max, was found to have no effects on circulating inflammatory markers in these obese patients. It is suggested that more intensive exercise may be necessary to affect systemic inflammation.

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Fasting decreases plasma FGF21 in obese subjects and the expression of FGF21 receptors in adipose tissue in both lean and obese subjects

Journal of Endocrinology ◽

10.1530/joe-18-0002 ◽

2018 ◽

Vol 239 (1) ◽

pp. 73-80 ◽

Cited By ~ 10

Author(s):

Eva B Nygaard ◽

Cathrine Ørskov ◽

Thomas Almdal ◽

Henrik Vestergaard ◽

Birgitte Andersen

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Lipid Metabolism ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Adipose Tissues ◽

Blood Samples ◽

Obese Subjects

Fibroblast growth factor 21 (FGF21) is a metabolic regulator of energy and lipid metabolism. FGF21 is highly expressed in liver while FGF21 receptors (beta-klotho (KLB) and FGFR1c) are highly expressed in white adipose tissues (WATs). Plasma FGF21 has been shown to be increased after 7–10 days of fasting but oppositely plasma FGF21 is also increased in obesity. The aim of this study was to measure the effect of 60 h of fasting on plasma FGF21 levels in obese and lean subjects and to determine the gene expression of KLB and FGFR1c in the subcutaneous WAT before, during and after 60 h of fasting. Eight obese (BMI >30 kg/m2) and seven lean subjects (BMI <25 kg/m2) were fasted for 60 h and blood samples were taken at time 0 and after 12, 36 and 60 h of fasting. A biopsy from the subcutaneous WAT was taken at time 0, 12 and 60 h of fasting. FGF21 was measured in plasma by an ELISA and mRNA expression of KLB and FGFR1c was measured in WAT by quantitative PCR (qPCR). The fast significantly decreased plasma FGF21 in obese subjects while no change in plasma FGF21 was observed in lean subjects. Interestingly, KLB was significantly decreased in WAT in response to fasting in both lean and obese subjects indicating a potential important adaptive regulation of KLB in response to fasting.

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