scholarly journals THE EFFECT OF ω-FATTY ACIDS ON mRNA EXPRESSION LEVEL OF PPARγ IN PATIENTS WITH GASTRIC ADENOCARCINOMA

2016 ◽  
Vol 38 (3) ◽  
pp. 191-194 ◽  
Author(s):  
A Hosseinzadeh ◽  
M H Somi ◽  
H Dolatkhah ◽  
A Esfahani ◽  
H S Kafil ◽  
...  

Background: The antineoplastic role of peroxisome proliferator-activated receptor gamma (PPARγ) ligandshas previously been demonstrated in several gastric cancer cell lines. Activation of PPARγ by polyunsaturated fatty acids (PUFAs) inhibits growth and proliferationof tumor cells. In this double-blind clinical study, we evaluate the effect of PUFAs on PPARγ mRNA expression in patients with gastric adenocarcinoma. Materials and Methods: A total of 34 chemotherapy-naive patients diagnosed with gastric adenocarcinoma were enrolled in the present study. According to treatment strategies, all subjects were divided into two groups, the first group (17 individuals) received cisplatin without supplements and the second group (17 individuals) received cisplatin plus orally administered PUFAs supplements for 3 weeks. The gastric biopsy samples were obtained from all participants before and after treatment, and PPARγ mRNA expression levels were evaluated by quantitative real-time polymerase chain reaction using validated reference genes. Results: Our findings revealed that PPARγ mRNA expression is significantly upregulated in group II afterreceiving cisplatin plus orally administered PUFAs supplements for three weeks (p < 0.0001), whereas PPARγ mRNA expression did not show significant alteration in group I after receiving cisplatin alone. Conclusion: The results of the study evidence that PPARγ may act as a potential target for the therapy of human gastric adenocarcinoma.

2021 ◽  
pp. 1-27
Author(s):  
Xiaojun Xiang ◽  
Shangzhe Han ◽  
Dan Xu ◽  
Qiuchi Chen ◽  
Renlei Ji ◽  
...  

Abstract Angiopoietin-like 4 (ANGPTL4) is a potent regulator of triacylglycerol metabolism but knowledge of the mechanisms underlying ANGPTL4 transcription in response to fatty acids is still limited in teleost. In this study, we explored the molecular characterization of ANGPTL4 and regulatory mechanisms of ANGPTL4 in response to fatty acids in large yellow croaker (Larimichthys crocea). Here, croaker angptl4 contained a 1416 bp open reading frame encoding a protein of 471 amino acids with highly conserved 12-amino acid consensus motif. Angptl4 was widely expressed in croaker, with the highest expression in the liver. In vitro, oleic and palmitic acids (OA and PA) treatments strongly increased angptl4 mRNA expression in croaker hepatocytes. Moreover, angptl4 expression was positively regulated by peroxisome proliferator-activated receptor family (PPAR-α, β and γ) and expression of pparγ was also significantly increased in response to OA and PA. Moreover, inhibition of PPARγ abrogated OA or PA-induced angptl4 mRNA expression. Beyond that, PA might increase angptl4 expression partly via the insulin signaling. Overall, the expression of ANGPTL4 is strongly upregulated by OA and PA via PPARγ in the liver of croaker, which contributes to improve the understanding of the regulatory mechanisms of ANGPTL4 in fish.


Author(s):  
Sara Moradi ◽  
Mohamadreza Alivand ◽  
Yaser KhajeBishak ◽  
Mohamad AsghariJafarabadi ◽  
Maedeh Alipour ◽  
...  

Abstract Background Omega3 fatty acids as a ligand of energy-related genes, have a role in metabolism, and energy expenditure. These effects are due to changes in the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and uncoupling protein2 (UCP2). This study evaluated the effect of omega3 supplements on PPARγ mRNA expression and UCP2 mRNA expression and protein levels, as regulators of energy metabolism, resting energy expenditure (REE), and appetite in athletes. Methods In a 3-week double-blind RCT in Tabriz, Iran, in 2019, 36 male athletes, age 21.86 (±3.15) y with 16.17 (±5.96)% body fat were randomized to either an intervention (2000 mg/day omega3; EPA: 360, DHA: 240) or placebo (2000 mg/day edible paraffin) groups. Appetite and REE were assessed before and after the intervention. PPARγ and UCP2 mRNA expression and UCP2 protein levels in blood were evaluated by standard methods. Results Results showed PPARγ mRNA levels, and UCP2 mRNA and protein levels increased in omega3 group (p < 0.05), as did REE (p < 0.05). Also, differences in the sensation of hunger or satiety were significant (p < 0.05). Conclusions Our findings showed that omega3 supplementation leads to the up-regulation of PPARγ and UCP2 expressions as the indicators of metabolism in healthy athletes.


Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4695-4704 ◽  
Author(s):  
Neus Pedraza ◽  
Meritxell Rosell ◽  
Joan Villarroya ◽  
Roser Iglesias ◽  
Frank J. Gonzalez ◽  
...  

Uncoupling protein-3 (UCP3) is a member of the mitochondrial carrier family expressed preferentially in skeletal muscle and heart. It appears to be involved in metabolic handling of fatty acids in a way that minimizes excessive production of reactive oxygen species. Fatty acids are powerful regulators of UCP3 gene transcription. We have found that the role of peroxisome proliferator-activated receptor-α (PPARα) on the control of UCP3 gene expression depends on the tissue and developmental stage. In adults, UCP3 mRNA expression is unaltered in skeletal muscle from PPARα-null mice both in basal conditions and under the stimulus of starvation. In contrast, UCP3 mRNA is down-regulated in adult heart both in fed and fasted PPARα-null mice. This occurs despite the increased levels of free fatty acids caused by fasting in PPARα-null mice. In neonates, PPARα-null mice show impaired UCP3 mRNA expression in skeletal muscle in response to milk intake, and this is not a result of reduced free fatty acid levels. The murine UCP3 promoter is activated by fatty acids through either PPARα or PPARδ but not by PPARγ or retinoid X receptor alone. PPARδ-dependent activation could be a potential compensatory mechanism to ensure appropriate expression of UCP3 gene in adult skeletal muscle in the absence of PPARα. However, among transcripts from other PPARα and PPARδ target genes, only those acutely induced by milk intake in wild-type neonates were altered in muscle or heart from PPARα-null neonates. Thus, PPARα-dependent regulation is required for appropriate gene regulation of UCP3 as part of the subset of fatty-acid-responsive genes in neonatal muscle and heart.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.


PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-15 ◽  
Author(s):  
Weimin He

The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR, Pro12Ala of PPAR2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPAR2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPAR2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPAR2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.


2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Huibin Tian ◽  
Jun Luo ◽  
Hengbo Shi ◽  
Xiaoying Chen ◽  
Jiao Wu ◽  
...  

Abstract A key member of the nuclear receptor superfamily is the peroxisome proliferator-activated receptor alpha (PPARA) isoform, which in nonruminants is closely associated with fatty acid oxidation. Whether PPARA plays a role in milk fatty acid synthesis in ruminants is unknown. The main objective of the present study was to use primary goat mammary epithelial cells (GMEC) to activate PPARA via the agonist WY-14643 (WY) or to silence it via transfection of small-interfering RNA (siRNA). Three copies of the peroxisome proliferator-activated receptor response element (PPRE) contained in a luciferase reporter vector were transfected into GMEC followed by incubation with WY at 0, 10, 20, 30, 50, or 100 µM. A dose of 50 µM WY was most effective at activating PPRE without influencing PPARA mRNA abundance. Transfecting siRNA targeting PPARA decreased its mRNA abundance to 20% and protein level to 50% of basal levels. Use of WY upregulated FASN, SCD1, ACSL1, DGAT1, FABP4, and CD36 (1.1-, 1.5-, 2-, 1.4-, 1.5-, and 5-fold, respectively), but downregulated DGAT2 and PGC1A (−20% and −40%, respectively) abundance. In contrast, triacylglycerol concentration decreased and the content and desaturation index of C16:1 and C18:1 increased. Thus, activation of PPARA via WY appeared to channel fatty acids away from esterification. Knockdown of PPARA via siRNA downregulated ACACA, SCD1, AGPAT6, CD36, HSL, and SREBF1 (−43%, −67%, −16%, −56%, −26%, and −29%, respectively), but upregulated ACSL1, DGAT2, FABP3, and PGC1A (2-, 1.4-, 1.3-, and 2.5-fold, respectively) mRNA abundance. A decrease in the content and desaturation index of C16:1 and C18:1 coupled with an increase in triacylglycerol content accompanied those effects at the mRNA level. Overall, data suggest that PPARA could promote the synthesis of MUFA in GMEC through its effects on mRNA abundance of genes related to fatty acid synthesis, oxidation, transport, and triacylglycerol synthesis.


2020 ◽  
Vol 128 (4) ◽  
pp. 768-777
Author(s):  
Robert Shute ◽  
Katherine Marshall ◽  
Megan Opichka ◽  
Halee Schnitzler ◽  
Brent Ruby ◽  
...  

Cold environmental temperatures during exercise and recovery alter the acute response to cellular signaling and training adaptations. Approximately 3 wk is required for cold temperature acclimation to occur. To determine the impact of cold environmental temperature on training adaptations, fitness measurements, and aerobic performance, two groups of 12 untrained male subjects completed 1 h of cycling in 16 temperature acclimation sessions in either a 7°C or 20°C environmental temperature. Fitness assessments before and after acclimation occurred at standard room temperature. Muscle biopsies were taken from the vastus lateralis muscle before and after training to assess molecular markers related to mitochondrial development. Peroxisome proliferator-activated receptor-γ coactivator 1α ( PGC-1α) mRNA was higher in 7°C than in 20°C in response to acute exercise before training ( P = 0.012) but not after training ( P = 0.813). PGC-1α mRNA was lower after training ( P < 0.001). BNIP3 was lower after training in the 7°C than in the 20°C group ( P = 0.017) but not before training ( P = 0.549). No other differences occurred between temperature groups in VEGF, ERRα, NRF1, NRF2, TFAM, PINK1, Parkin, or BNIP3L mRNAs ( P > 0.05). PGC-1α protein and mtDNA were not different before training, after training, or between temperatures ( P > 0.05). Cycling power increased during the daily training ( P < 0.001) but was not different between temperatures ( P = 0.169). V̇o2peak increased with training ( P < 0.001) but was not different between temperature groups ( P = 0.460). These data indicate that a 3-wk period of acclimation/training in cold environmental temperatures alters PGC-1α gene expression acutely but this difference is not manifested in a greater increase in V̇o2peak and is dissipated as acclimation takes place. NEW & NOTEWORTHY This study examines the adaptive response of cellular signaling during exercise in cold environmental temperatures. We demonstrate that peroxisome proliferator-activated receptor-γ coactivator 1α mRNA is different between cold and room temperature environments before training but after training this difference no longer exists. This initial difference in transcriptional response between temperatures does not lead to differences in performance measures or increases in protein or mitochondria.


2018 ◽  
Vol 25 (3) ◽  
pp. 219
Author(s):  
Bianca Codrina Morarasu ◽  
Raluca Ecaterina Haliga ◽  
Daniel Timofte ◽  
Ioana Hristov ◽  
Iustina Silivestru-Cretu ◽  
...  

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1259 ◽  
Author(s):  
Garima Maheshwari ◽  
Robert Ringseis ◽  
Gaiping Wen ◽  
Denise K. Gessner ◽  
Johanna Rost ◽  
...  

The study aimed to test the hypothesis that monomethyl branched-chain fatty acids (BCFAs) and a lipid extract of Conidiobolus heterosporus (CHLE), rich in monomethyl BCFAs, are able to activate the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Rat Fao cells were incubated with the monomethyl BCFAs 12-methyltridecanoic acid (MTriA), 12-methyltetradecanoic acid (MTA), isopalmitic acid (IPA) and 14-methylhexadecanoic acid (MHD), and the direct activation of PPARalpha was evaluated by reporter gene assay using a PPARalpha responsive reporter gene. Furthermore, Fao cells were incubated with different concentrations of the CHLE and PPARalpha activation was also evaluated by using the reporter gene assay, and by determining the mRNA concentrations of selected PPARalpha target genes by real-time RT-PCR. The reporter gene assay revealed that IPA and the CHLE, but not MTriA, MHD and MTA, activate the PPARalpha responsive reporter gene. CHLE dose-dependently increased mRNA concentrations of the PPARalpha target genes acyl-CoA oxidase (ACOX1), cytochrome P450 4A1 (CYP4A1), carnitine palmitoyltransferase 1A (CPT1A) and solute carrier family 22 (organic cation/carnitine transporter), member 5 (SLC22A5). In conclusion, the monomethyl BCFA IPA is a potent PPARalpha activator. CHLE activates PPARalpha-dependent gene expression in Fao cells, an effect that is possibly mediated by IPA.


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