Inhibition of Peroxisome Proliferator-Activated Receptor Gamma Prevents the Melanogenesis in Murine B16/F10 Melanoma Cells

The purpose of this study was to investigate if PPARγplays a role in the melanogenesis. B16/F10 cells were divided into five groups: control, melanin stimulating hormone (α-MSH),α-MSH+retinol,α-MSH+GW9662 (PPARγantagonist), and GW9662. Cells in the control group were cultured in the Dulbecco’s modified Eagle’s medium (DMEM) for 48 hrs. To initiate the melanogenesis, cells in allα-MSH groups were cultured in medium containingα-MSH (10 nM) for 48 hrs. Cells were treated simultaneously with retinol (5 μM) in theα-MSH+retinol group. Instead of retinol, GW9662 (10 μM) was cocultured in theα-MSH+GW9662 group. Cells in the final group were cultured in the DMEM with GW9662. All the analyses were carried out 48 hours after treatments. Theα-MSH was able to increase cell number, melanin production, and the activity of tyrosinase, the limiting enzyme in melanogenesis. Theseα-MSH-induced changes were prevented either by retinol or by GW9662. Further analyses of the activities of antioxidant enzymes including glutathione, catalase, and the superoxide dismutase (SOD) showed thatα-MSH treatment raised the activity of SOD which was dependent on PPARγlevel. According to our results, theα-MSH-induced melanogenesis was PPARγdependent, which also modulated the expression of SOD.

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Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice

BioMed Research International ◽

10.1155/2020/6159407 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yeram Park ◽

Deunsol Hwang ◽

Hun-Young Park ◽

Jisu Kim ◽

Kiwon Lim

Keyword(s):

Glucose Metabolism ◽

Energy Expenditure ◽

Pyruvate Dehydrogenase ◽

Hypoxic Condition ◽

Open Circuit ◽

Pyruvate Dehydrogenase Kinase ◽

Hypoxic Exposure ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions. Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspired O2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspired O2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle. Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP; 1.9±0.9 vs. −0.3±0.9; p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1α protein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group. Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.

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Alteration in the oxidative status of Drosophila melanogaster Meigen (Diptera: Drosophilidae) fed with a diet containing Centaurea depressa M. Bieb. (Asteraceae)

Animal Biology ◽

10.1163/15707563-20191153 ◽

2020 ◽

Vol 70 (2) ◽

pp. 227-237

Author(s):

Eda Güneş

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Total Protein ◽

Protein Carbonyl ◽

Control Group ◽

Carbonyl Content ◽

Protein Carbonyl Content ◽

Freeze Dried ◽

Dried Extract

Abstract The aim of the this study was to evaluate the effects of fresh, dried and freeze-dried Centaurea depressa M. Bieb. (Asteraceae) on the oxidant and antioxidant status of the model organism D. melanogaster Meigen (Diptera: Drosophilidae) experimentally. The study was carried out from 2016 to 2019, and plant leaf extracts (0-50 mg/l) were added to insect standard artificial diets. The total protein, protein carbonyl content and glutathione-S-transferase, superoxide dismutase and catalase activities were quantified at the insect’s third larval stage. Our data showed that protein carbonyl content varied from 2.70 nmol/mg protein in the control group to 59.11 nmol/mg protein in the group fed with fresh leaf extract signifying induction of oxidative stress. All extracts increased the levels of all antioxidant enzymes and decreased the amounts of total protein. Meanwhile, the group fed with the freeze-dried extract showed no significant difference in the levels of total protein and protein carbonyl content except at the 50 mg/l concentration of the extract. Moreover, this group had superoxide dismutase and catalase activities 4 to 5 times higher than in the control group. In conclusion, induction of oxidative stress indicates that the fresh form of C. depressa leaves may have potential as a natural pesticide, whereas induction of endogenous antioxidant enzymes by the freeze-dried extract suggest its potential as an antioxidant.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20051153 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1153 ◽

Cited By ~ 11

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.

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The Effect of Diabetes Mellitus, Insulin, and Thiazolidinediones on Bone Histomorphometry in Streptozotocin-induced Diabetic Postmenopausal Wistar Rats

Sudan Journal of Medical Sciences ◽

10.18502/sjms.v16i1.8937 ◽

2021 ◽

pp. 56-69

Author(s):

Derya Köseoğlu ◽

Gülnur Take ◽

Banu Aktaş Yılmaz ◽

Erdal Kan ◽

Nuri Çakır

Keyword(s):

Diabetes Mellitus ◽

Bone Histomorphometry ◽

Wistar Rats ◽

Treated Group ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Trabecular Thickness ◽

Skeletal Disease ◽

Negative Effect

Background: Osteoporosis is a metabolic skeletal disease with low bone mass and bone microarchitectural disorganization. Thiazolidinediones (TZD) increase insulin sensitivity through activation of peroxisome proliferator-activated receptor gamma (PPARγ). One of the most important side effects of this drugs is its effects on bone, especially in postmenopausal women. The purpose of this study was to evaluate the effect of diabetes mellitus (DM), insulin, and TZDs on bone in postmenopausal Wistar rats. Methods: Sixteen postmenopausal Wistar rats were divided into four groups: (i) control group, (ii) Streptozotocin-induced DM group without treatment, (iii) Streptozotocin-induced DM group with insulin therapy, and (iv) Streptozotocin-induced DM group receiving rosiglitazone. Pictures of the obtained samples were taken under computer-equipped photo-light microscope, and bone tissue ratios were calculated in an area of 1 mm2. In this area, trabecular thicknesses were measured from six randomly selected regions. In addition, femoral neck regions were determined by measuring the farthest distance. Results: Compared to the control group, trabecular thicknesses were decreased in the uncontrolled DM and rosiglitazone groups. In the rosiglitazone-treated group, trabecular thickness was decreased compared to the uncontrolled DM group. The histological examination of the bones showed that uncontrolled DM and rosiglitazone treatment negatively affected the osteoblast and osteocyte activity. Insulin-treated group had a similar histologic examination compared to the control group. Conclusion: Our study showed that DM had unfavorable effects on bones, and rosiglitazone further exerts this effect. However, the negative effect of DM may be neutralized with the use of insulin. Keywords: diabetes mellitus, bone, osteoporosis, bone histomorphometry, rosiglitazone, insulin, thiazolidinediones

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Regulator 1-Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Signaling Pathway in Investigating the Pathological Characteristics and Molecular Mechanism of Liver Cirrhosis Complicated by Acute Kidney Injury

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2859 ◽

2022 ◽

Vol 12 (1) ◽

pp. 112-120

Author(s):

Jieqi Gong ◽

Huanhua Lu

Keyword(s):

Acute Kidney Injury ◽

Liver Cirrhosis ◽

Signaling Pathway ◽

Molecular Mechanism ◽

Kidney Injury ◽

Male Rats ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Duct Ligation

The objective of this study was to investigate the molecular mechanism of the histopathological characteristics of liver cirrhosis (LC) complicated with acute kidney injury (AKI) and the signaling pathway of silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) during the pathogenesis of LC. 20 healthy male rats with AKI complicated by laparoscopic cholecystectomy were selected and divided randomly into control group (C group), lipopolysaccharide (LPS) group, bile duct ligation (BDL) group, and model group (lipopolysaccharide+BDL) (D group). The indexes of all the rats were determined, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), sarcoplasmic enzyme (Scr), and blood urea nitrogen (BUN); the SIRT1 and PGC-1α expressions in renal tissues of rats from each group was detected. Results showed that the AST and ALT levels in BDL group and D group were higher markedly than those before surgery (P < 0.05). The serum levels of Scr and BUN in D group 4 hours after LPS injection increased hugely compared with before injection (P < 0.05). Compared with BDL group, the protein levels of SIRT1 and PGC-1α in renal tissue of group D were decreased sharply (P < 0.05), and the SIRT1 protein expression was positively correlated with PGC-1α (r = 0.836 and P < 0.01). When LC were complicated with AKI, SIRT1 activity was reduced and PGC-1α expression was inhibited. Moreover, SIRT1-PGC-1α signaling pathway played a protective role in pathogenesis of LC complicated with AKI.

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Chronic rosiglitazone treatment restores AMPKα2 activity in insulin-resistant rat skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00096.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. E251-E257 ◽

Cited By ~ 40

Author(s):

Sarah J. Lessard ◽

Zhi-Ping Chen ◽

Matthew J. Watt ◽

Michael Hashem ◽

Julianne J. Reid ◽

...

Keyword(s):

Skeletal Muscle ◽

Zucker Rats ◽

Control Group ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Ampk Signaling ◽

Palmitate Oxidation ◽

Insulin Resistant ◽

Obese Zucker Rats

Rosiglitazone (RSG) is an insulin-sensitizing thiazolidinedione (TZD) that exerts peroxisome proliferator-activated receptor-γ (PPARγ)-dependent and -independent effects. We tested the hypothesis that part of the insulin-sensitizing effect of RSG is mediated through the action of AMP-activated protein kinase (AMPK). First, we determined the effect of acute (30–60 min) incubation of L6 myotubes with RSG on AMPK regulation and palmitate oxidation. Compared with control (DMSO), 200 μM RSG increased ( P < 0.05) AMPKα1 activity and phosphorylation of AMPK (Thr172). In addition, acetyl-CoA carboxylase (Ser218) phosphorylation and palmitate oxidation were increased ( P < 0.05) in these cells. To investigate the effects of chronic RSG treatment on AMPK regulation in skeletal muscle in vivo, obese Zucker rats were randomly allocated into two experimental groups: control and RSG. Lean Zucker rats were treated with vehicle and acted as a control group for obese Zucker rats. Rats were dosed daily for 6 wk with either vehicle (0.5% carboxymethylcellulose, 100 μl/100 g body mass), or 3 mg/kg RSG. AMPKα1 activity was similar in muscle from lean and obese animals and was unaffected by RSG treatment. AMPKα2 activity was ∼25% lower in obese vs. lean animals ( P < 0.05) but was normalized to control values after RSG treatment. ACC phosphorylation was decreased with obesity ( P < 0.05) but restored to the level of lean controls with RSG treatment. Our data demonstrate that RSG restores AMPK signaling in skeletal muscle of insulin-resistant obese Zucker rats.

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Prenatal androgen excess alters the uterine peroxisome proliferator-activated receptor (PPAR) system

Reproduction Fertility and Development ◽

10.1071/rd18432 ◽

2019 ◽

Vol 31 (8) ◽

pp. 1401

Author(s):

Silvana R. Ferreira ◽

Leandro M. Vélez ◽

Maria F. Heber ◽

Giselle A. Abruzzese ◽

Alicia B. Motta

Keyword(s):

Fetal Programming ◽

Female Offspring ◽

Control Group ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Androgen Excess ◽

Peroxisome Proliferator Activated Receptor ◽

Peroxisome Proliferator Activated Receptors ◽

Pg E2 ◽

Prenatal Androgen

It is known that androgen excess induces changes in fetal programming that affect several physiological pathways. Peroxisome proliferator-activated receptors (PPARs) α, δ and γ are key mediators of female reproductive functions, in particular in uterine tissues. Thus, we aimed to study the effect of prenatal hyperandrogenisation on the uterine PPAR system. Rats were treated with 2mg testosterone from Day 16 to 19 of pregnancy. Female offspring (PH group) were followed until 90 days of life, when they were killed. The PH group exhibited an anovulatory phenotype. We quantified uterine mRNA levels of PPARα (Ppara), PPARδ (Ppard), PPARγ (Pparg), their regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a) and nuclear receptor co-repressor 1 (Ncor1) and cyclo-oxygenase (COX)-2 (Ptgs2), and assessed the lipid peroxidation (LP) index and levels of glutathione (GSH) and prostaglandin (PG) E2. The PH group showed decreased levels of all uterine PPAR isoforms compared with the control group. In addition, PGE2 and Ptgs2 levels were increased in the PH group, which led to a uterine proinflammatory environment, as was LP, which led to a pro-oxidant status that GSH was not able to compensate for. These results suggest that prenatal exposure to androgen excess has a fetal programming effect that affects the gene expression of PPAR isoforms, and creates a misbalanced oxidant–antioxidant state and a proinflammatory status.

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PPARγAgonists: Blood Pressure and Edema

PPAR Research ◽

10.1155/2010/785369 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Bonnie L. Blazer-Yost

Keyword(s):

Blood Pressure ◽

Fluid Retention ◽

Peroxisome Proliferator ◽

Positive Aspect ◽

Drug Induced ◽

Peroxisome Proliferator Activated Receptor ◽

Alternative Pathways ◽

Blood Pressure Data ◽

Induced Changes

Peroxisome proliferator activated receptorγ(PPARγ) agonists are widely used in the treatment of type 2 diabetes. Side effects of drug treatment include both fluid retention and a lowering of blood pressure. Data from animal and human studies suggest that these effects arise, at least in part, from drug-induced changes in the kidney. In order to capitalize on the positive aspect (lowering of blood pressure) and exclude the negative one (fluid retention), it is necessary to understand the mechanisms of action underlying each of the effects. When interpreted with known physiological principles, current hypotheses regarding potential mechanisms produce enigmas that are difficult to resolve. This paper is a summary of the current understanding of PPARγagonist effects on both blood pressure and fluid retention from a renal perspective and concludes with the newest studies that suggest alternative pathways within the kidney that could contribute to the observed drug-induced effects.

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Effect of Linseed Oil Dietary Supplementation on Fatty Acid Composition and Gene Expression in Adipose Tissue of Growing Goats

BioMed Research International ◽

10.1155/2013/194625 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 27

Author(s):

M. Ebrahimi ◽

M. A. Rajion ◽

Y. M. Goh ◽

A. Q. Sazili ◽

J. T. Schonewille

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Fatty Acid ◽

Subcutaneous Adipose Tissue ◽

Linseed Oil ◽

Control Group ◽

Peroxisome Proliferator ◽

Potential Health ◽

Peroxisome Proliferator Activated Receptor ◽

Subcutaneous Adipose

This study was conducted to determine the effects of feeding oil palm frond silage based diets with added linseed oil (LO) containing highα-linolenic acid (C18:3n-3), namely, high LO (HLO), low LO (LLO), and without LO as the control group (CON) on the fatty acid (FA) composition of subcutaneous adipose tissue and the gene expression of peroxisome proliferator-activated receptor (PPAR)α, PPAR-γ, and stearoyl-CoA desaturase (SCD) in Boer goats. The proportion of C18:3n-3 in subcutaneous adipose tissue was increased (P<0.01) by increasing the LO in the diet, suggesting that the FA from HLO might have escaped ruminal biohydrogenation. Animals fed HLO diets had lower proportions of C18:1 trans-11, C18:2n-6, CLA cis-9 trans-11, and C20:4n-6 and higher proportions of C18:3n-3, C22:5n-3, and C22:6n-3 in the subcutaneous adipose tissue than animals fed the CON diets, resulting in a decreased n-6:n-3 fatty acid ratio (FAR) in the tissue. In addition, feeding the HLO diet upregulated the expression of PPAR-γ(P<0.05) but downregulated the expression of SCD (P<0.05) in the adipose tissue. The results of the present study show that LO can be safely incorporated in the diets of goats to enrich goat meat with potential health beneficial FA (i.e., n-3 FA).

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Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition

Journal of Obesity ◽

10.1155/2013/312153 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 16

Author(s):

Heidi N. Bagley ◽

Yan Wang ◽

Michael S. Campbell ◽

Xing Yu ◽

Robert H. Lane ◽

...

Keyword(s):

Docosahexaenoic Acid ◽

Receptor Expression ◽

Male Rats ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Pregnancy And Lactation ◽

Maternal Supplementation ◽

Induced Changes ◽

Adipose Dysfunction ◽

Visceral Adipose

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγincreases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPARγagonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPARγexpression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

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