scholarly journals Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients

2019 ◽  
Vol 20 (5) ◽  
pp. 1153 ◽  
Author(s):  
Nunzia D’Onofrio ◽  
Gorizio Pieretti ◽  
Feliciano Ciccarelli ◽  
Antonio Gambardella ◽  
Nicola Passariello ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Abdominal Fat ◽  
Control Group ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metformin Therapy ◽  
Ppar Γ ◽  
Visceral Abdominal Fat ◽  
Factor Α

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

scholarly journals Gene expressions of de novo hepatic lipogenesis in feline hepatic lipidosis

2019 ◽  
Vol 22 (6) ◽  
pp. 500-505
Author(s):  
Chiara Valtolina ◽  
Joris H Robben ◽  
Monique E van Wolferen ◽  
Hedwig S Kruitwagen ◽  
Ronald J Corbee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Liver Tissue ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Hepatic Lipidosis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Objectives The aim of this study was to evaluate if de novo hepatic lipid synthesis contributes to fatty acid overload in the liver of cats with feline hepatic lipidosis (FHL). Methods Lipogenic gene expression of peroxisome proliferator-activated receptor-alpha ( PPAR-α), peroxisome proliferator-activated receptor-gamma ( PPAR-γ), fatty acid synthase ( FASN) and sterol regulatory element-binding factor ( SREBF1) were evaluated using quantitative RT-PCR in liver tissue of six cats with FHL and compared with the liver tissue of eight healthy cats. Results In liver tissue, PPAR-α, PPAR-γ and FASN mRNA expression levels were not significantly different ( P >0.12, P >0.89 and P >0.5, respectively) in the FHL group compared with the control group. SREBF1 gene expression was downregulated around 10-fold in the FHL group vs the control group ( P = 0.039). Conclusions and relevance The downregulation of SREBF1 in the liver tissue of cats with FHL does not support the hypothesis that de novo lipogenesis in the liver is an important pathway of fatty acid accumulation in FHL.

scholarly journals Hypophagia and metabolic adaptations in mice with defective ATGL-mediated lipolysis cause resistance to HFD-induced obesity

2015 ◽  
Vol 112 (45) ◽  
pp. 13850-13855 ◽  
Author(s):  
Renate Schreiber ◽  
Peter Hofer ◽  
Ulrike Taschler ◽  
Peter J. Voshol ◽  
Gerald N. Rechberger ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Lipid Synthesis ◽  
Protective Mechanism ◽  
Peroxisome Proliferator ◽  
Lipid Storage Disease ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Element Binding Protein ◽  
Neutral Lipid Storage Disease ◽  
Sterol Regulatory Element

Adipose triglyceride lipase (ATGL) initiates intracellular triglyceride (TG) catabolism. In humans, ATGL deficiency causes neutral lipid storage disease with myopathy (NLSDM) characterized by a systemic TG accumulation. Mice with a genetic deletion of ATGL (AKO) also accumulate TG in many tissues. However, neither NLSDM patients nor AKO mice are exceedingly obese. This phenotype is unexpected considering the importance of the enzyme for TG catabolism in white adipose tissue (WAT). In this study, we identified the counteracting mechanisms that prevent excessive obesity in the absence of ATGL. We used “healthy” AKO mice expressing ATGL exclusively in cardiomyocytes (AKO/cTg) to circumvent the cardiomyopathy and premature lethality observed in AKO mice. AKO/cTg mice were protected from high-fat diet (HFD)-induced obesity despite complete ATGL deficiency in WAT and normal adipocyte differentiation. AKO/cTg mice were highly insulin sensitive under hyperinsulinemic-euglycemic clamp conditions, eliminating insulin insensitivity as a possible protective mechanism. Instead, reduced food intake and altered signaling by peroxisome proliferator-activated receptor-gamma (PPAR-γ) and sterol regulatory element binding protein-1c in WAT accounted for the phenotype. These adaptations led to reduced lipid synthesis and storage in WAT of HFD-fed AKO/cTg mice. Treatment with the PPAR-γ agonist rosiglitazone reversed the phenotype. These results argue for the existence of an adaptive interdependence between lipolysis and lipid synthesis. Pharmacological inhibition of ATGL may prove useful to prevent HFD-induced obesity and insulin resistance.

scholarly journals Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors

2021 ◽  
Vol 43 (3) ◽  
pp. 2082-2097
Author(s):  
Jelena Jakab ◽  
Milorad Zjalić ◽  
Štefica Mikšić ◽  
Ivan Tušek ◽  
Vesna Ćosić ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Element ◽  
Combined Treatment ◽  
Inhibitory Effect ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein ◽  
Oil Red O Staining ◽  
Oil Red O

Obesity is a multifactorial chronic disease characterized by the excessive accumulation of fat in adipose tissue driven by hypertrophy and hyperplasia of adipocytes through adipogenesis. Adipogenesis plays a key role in the development of obesity and related metabolic disorders, which makes it potential target for the therapeutic approach to obesity. An increasing number of studies confirm the pleiotropic action of the combined treatment with metformin and statins, suggesting their anti-hypertensive, anti-inflammatory, and anti-adipogenic effect. The aim of this study was to analyze the effect of different doses of metformin (MET) and simvastatin (SIM) on the expression of key transcription factors of adipogenesis. Mouse 3T3-L1 preadipocytes were induced to differentiation in adipogenic medium with sustained MET and SIM treatment to assess the effect on adipogenesis. Nine days after initiating adipogenesis, the cells were prepared for further experiments, including Oil Red O staining, RT-PCR, Western blotting, and immunocytochemistry. Treating the cells with the combination of MET and SIM slightly reduced the intensity of Oil Red O staining compared with the control group, and down-regulated mRNA and protein expression of PPARγ, C/EBPα, and SREBP-1C. In conclusion, the inhibitory effect of MET and SIM on adipocyte differentiation, as indicated by decreased lipid accumulation, appears to be mediated through the down-regulation of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding pro-tein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1C).

Thiazolidinedione-induced effects beyond glycaemic control

2002 ◽  
Vol 2 (1_suppl) ◽  
pp. S24-S27 ◽  
Author(s):  
Ulf Smith
Keyword(s):  
Insulin Resistance ◽  
Nuclear Receptors ◽  
Tumour Necrosis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Tumour Necrosis Factor Α ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Factor Α ◽  
Necrosis Factor

The thiazolidinediones exert their insulin sensitising effect by binding to the nuclear receptors (transcription factors) peroxisome proliferator activated receptor (PPAR) γ and, to varying degrees, to PPARα. Several different genes are activated by thiazolidinediones, many of which contribute to the increase in insulin sensitivity (eg. an increase in glucose uptake and utilisation, a decrease in gluconeogenesis and in insulin-antagonistic cytokines, such as tumour necrosis factor α). Activation of other genes indirectly reduces insulin resistance by, for example, increasing free fatty acid (FFA) uptake and oxidation resulting in lower circulating FFA levels. The action of thiazolidinediones at PPARγ is generally responsible for their insulin sensitising effects while action at PPARα contributes to their lipid lowering effects. Therefore, the relative affinities of the different thiazolidinediones for PPARγ and PPARα will also lead to a different spectrum of actions for each agent.

Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) Agonist Increases Plasma Adiponectin Levels in Type 2 Diabetic Patients with Proteinuria

Endocrine ◽  
2004 ◽  
Vol 25 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Mahmut Ilker Yilmaz ◽  
Alper Sonmez ◽  
Kayser Caglar ◽  
Deniz Engin Gok ◽  
Tayfun Eyileten ◽  
...  
Keyword(s):  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Type 2 Diabetic Patients ◽  
Peroxisome Proliferator Activated Receptor ◽  
Plasma Adiponectin ◽  
Ppar Γ ◽  
Type 2 Diabetic

scholarly journals Nonylphenol Promotes the Differentiation of 3T3-L1 Preadipocytes

2021 ◽  
Author(s):  
lan Tang ◽  
Jie Xu ◽  
Jie Yu ◽  
Mei Wen Li
Keyword(s):  
Late Stage ◽  
Lipid Droplets ◽  
Binding Protein ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Induced Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein

Abstract BackgroundNonylphenol (NP) induces obesity, we elucidated the influence of NP on the differentiation of 3T3-L1 preadipocytes and characterize the key stages in the underlying mechanism.Methods3T3-L1 preadipocytes were cultured until contact inhibition occurred and subsequently induced to differentiate using the MDI (methylisobutylxanthine, dexamethasone, and insulin) induction protocol. The cells were exposed to NP during the middle and late stages of the MDI-induced differentiation. After 24 h of exposure to NP, cell growth and differentiation were evaluated under an inverted phase-contrast microscope, lipid deposition was assessed by Oil Red O (ORO) staining, and the levels of the lipid-metabolism–related proteins CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthesis (FAS), peroxisome proliferator-activated receptor γ (PPARγ), and sterol regulatory element binding protein 1 (SREBP1) were determined by western blotting.Results1) Compared with the control group, the lipid droplets in the NP-treated cells were significantly more abundant and bigger,and the levels of C/EBPα, FAS, PPARγ and SREBP1 were significantly higher (P < .001). 2) The intensity of ORO staining was stronger and there were more intensely stained lipid droplets in the NP-treated cells during the middle stages than the late stage，the levels of the C/EBPα, FAS, PPARγ and SREBP1 during the middle stages were approximately higher than those during the late stage (P < .001). ConclusionNP promotes proliferation, differentiation, and lipid accumulation in 3T3-L1 preadipocytes, and increases the expression of the C/EBPα, FAS, PPARγ and SREBP1，and NP mainly promotes the proliferation and differentiation of 3T3-L1 preadipocytes during the middle stages of the MDI-induced differentiation.

scholarly journals Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)

2011 ◽  
Vol 4 ◽  
pp. CMAMD.S5951 ◽  
Author(s):  
Dina Shahin ◽  
Ehab El Toraby ◽  
Hala Abdel-Malek ◽  
Vivian Boshra ◽  
Ayman Z. Elsamanoudy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treated Group ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Das28 Score ◽  
Peroxisome Proliferator Activated Receptor ◽  
Reactive Protein ◽  
Usual Treatment ◽  
Ppar Γ

Objective To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical. Methods Experimentally: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months. Results Pioglitazone produced a significant improvement of serum oxidative stress parameters ( P < 0.05), and inflammatory cytokines in the treated arthritic group ( P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 ( P = 0.001) and C-reactive protein ( P < 0.0001) compared to placebo group. Conclusion The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.

Sign in / Sign up

Export Citation Format

Share Document