• 대한의생명과학회지
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• 제12권2호
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• pp.65-72
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• 2006

Thiazolidinediones (TZDs) are widely used antidiabetic drugs that activate the nuclear peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$, and thereby improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin resistance, and cardiovascular disease. To determine whether the $PPAR{\gamma}$ ligand troglitazone regulates lipid metabolism with sexual dimorphism, we examined the effects of troglitazone on circulating lipids, body weight and the expression of hepatic genes responsible for lipid metabolism in both sexes of C57BL/6J mice. Compared to mice fed a low fat control diet, both sexes of mice fed a troglitazone-treated low fat diet for 14 weeks did not exhibit changes in body weight gain, serum total cholesterol, HDL-cholesterol and LDL-cholesterol levels. However, serum triglycerides were significantly reduced in both sexes of mice, although these effects were more pronounced among males. Furthermore, troglitazone regulated the expression of hepatic genes critical for lipid and lipoprotein metabolism, the magnitudes of which were much higher in males compared to females, as evidenced by results for increased acyl-CoA oxidase and decreased apolipoprotein C-III mRMA levels. These results suggest that $PPAR{\gamma}$ activator troglitazone may exert sexually dimorphic control of serum triglycerides in part through the differential activation of $PPAR{\gamma}$ in liver between male and female mice.

• Archives of Pharmacal Research
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• 제28권2호
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• pp.142-150
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• 2005

The synthesis and structure-activity relationships of a novel series of substituted quercetins that activates peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) are reported. The $PPAR{\gamma}$ agonistic activity of the most potent compound in this series is comparable to that of the thiazolidinedione-based antidiabetic drugs currently in clinical use.

• BMB Reports
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• 제47권11호
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• pp.599-608
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• 2014

As the prevalence of obesity has increased explosively over the last several decades, associated metabolic disorders, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases, have been also increased. Thus, new strategies for preventing and treating them are needed. The nuclear peroxisome proliferator-activated receptors (PPARs) are involved fundamentally in regulating energy homeostasis; thus, they have been considered attractive drug targets for addressing metabolic disorders. Among the PPARs, $PPAR{\gamma}$ is a master regulator of gene expression for metabolism, inflammation, and other pathways in many cell types, especially adipocytes. It is a physiological receptor of the potent anti-diabetic drugs of the thiazolidinediones (TZDs) class, including rosiglitazone (Avandia). However, TZDs have undesirable and severe side effects, such as weight gain, fluid retention, and cardiovascular dysfunction. Recently, many reports have suggested that $PPAR{\gamma}$ could be modulated by post-translational modifications (PTMs), and modulation of PTM has been considered as novel approaches for treating metabolic disorders with fewer side effects than the TZDs. In this review, we discuss how PTM of $PPAR{\gamma}$ may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of $PPAR{\gamma}$.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.187.1-187.1
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• 2003

Type 2 diabetes is characterized by high level of blood glucose and insulin and impaired action. In recent years, the treatment of type 2 diabetes has been revolutionized with the advent of thiazolidinedione (TZD) class of molecules that ameliorate insulin resistance and thereby normalize elevated blood glucose levels. These TZDs are synthetic, high-affinity ligands of peroxisome proliferator activated receptor-gamma (PPAR${\gamma}$); a member of the nuclear receptor family that controls the expression of genes in the target tissues of insulin action. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.321-331
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• 2021

Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.

• Animal Bioscience
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• 제34권4호
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• pp.662-669
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• 2021

Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated. Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (FADS2), peroxisome proliferator activated receptor gamma (PPARγ), and insulin-like growth factor 1 (IGF1) genes was analysed by means of quantitative reverse transcription polymerase chain reaction. Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic FADS2 levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The PPARγ expression was lower (p<0.05), whereas IGF1 was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in FADS2, PPARγ, and IGF1 gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control. Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased FADS2 expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased PPARγ expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased IGF1 expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5875-5878
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• 2012

Background: Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) is a ligand dependent transcription factor involved in various processes, including carcinogenesis. We aimed to investigate any possible association of the $PPAR{\gamma}$ Pro12Ala (rs1801282) polymorphism with risk of developing gastric cancer (GC). Patients and Methods: A hospital based case control study was designed covering 50 patients with GC and 120 healthy controls. The frequencies of $PPAR{\gamma}$ Pro12Ala (rs1801282) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The Ala12 allele of the $PPAR{\gamma}$ Pro12Ala G gene was associated with a 1.95 fold increased risk of GC development (p: 0.022; 95% CI: 1.58-2.40). Subgroup analyses showed that the same allele was also associated with metastasis (p: 0.000; OR:4.09; 95%CI:2.273-7.368) and differentiation (p: 0.004; OR:1.95; 95%CI:1.335-2.875) in patients with GC. Conclusion: This study suggests that the $PPAR{\gamma}$ Pro12Ala G (Ala12) allele might be associated with development, differentiation and metastatic process of GC in the Turkish population. Further studies conducted in larger study groups and in different ethnic populations will be needed to clarify the exact role of the $PPAR{\gamma}$ Pro12Ala polymorphism in GC.

• 한방안이비인후피부과학회지
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• 제23권2호
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• pp.109-124
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• 2010

Objectives : The aim of this study is to investigate the antiallergic effects of YTT on allergic rhinitis by regulation of peroxisome proliferator-activated receptor gamma (PPAR-$\gamma$). Methods : The thirty rats were divided into three groups : normal group, control (allergic rhinitis elicited) group, sample (Yeotaectonggi-tang treated after allergic rhinitis elicitation) group. To induce allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1% ovalbumin(OVA) solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1% ovalbumin(OVA) solution 3 times at intervals of 2 days. After that time rats in sample group were oral administration treated by YTT for 7days. The change of the amounts of eosinophil, substance P, MIP-2, PPAR-$\gamma$, IL-4, iNOS were observed in each group. we used the statistical method of ANOVA test(p<0.05). Results : The number of eosinophil in sample group noticeably decreased than control group. And the decrease of substance P and MIP-2 positive reaction were observed in mucosa. YTT inhibited IL-4 and iNOS production, mucus secretion, activation of mast cells and fibrosis remodeling by regulation of PPAR-$\gamma$ activation. Conclusion : According to the above results, it is considered that YTT mitigated mucosa damage on the mice model with allergic rhinitis by regulation of PPAR-$\gamma$.

• Biomolecules & Therapeutics
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• 제23권3호
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• pp.218-224
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• 2015

Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB) receptors, transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and peroxisome proliferator-activated receptor ${\gamma}$($PPAR{\gamma}$). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the $CB_1$ receptor, TRPV1 and $PPAR{\gamma}$. In this study, the effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N-arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA whereas inhibited by NADA. No change was observed by the treatment of non-cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the regulation of adipogenesis is associated with their effects on $PPAR{\gamma}$ transactivation. AEA can directly activate $PPAR{\gamma}$. The effect of AEA on $PPAR{\gamma}$ in hBM-MSCs may prevail over that on the $CB_1$ receptor mediated signal transduction, giving rise to the AEA-induced promotion of adipogenesis. In contrast, NADA had no effect on the $PPAR{\gamma}$ activity in the $PPAR{\gamma}$ transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a $CB_1$ antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM-MSCs, which may be interpreted as the result of the inverse agonism of the $CB_1$ receptor. This result suggests that the constantly active $CB_1$ receptor may contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the selective $CB_1$ agonists that are unable to affect cellular $PPAR{\gamma}$ activity inhibit adipogenesis in hBM-MSCs.

• Asian-Australasian Journal of Animal Sciences
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• 제28권8호
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• pp.1075-1083
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• 2015

Adipose tissue deposited within muscle fibers, known as intramuscular fat (IMF or marbling), is a major determinant of meat quality and thereby affects its economic value. The biological mechanisms that determine IMF content are therefore of interest. In this study, 48 genes involved in the bovine peroxisome proliferator-activated receptor signaling pathway, which is involved in lipid metabolism, were investigated to identify candidate genes associated with IMF in the longissimus dorsi of Hanwoo (Korean cattle). Ten genes, retinoid X receptor alpha, peroxisome proliferator-activated receptor gamma (PPARG), phospholipid transfer protein, stearoyl-CoA desaturase, nuclear receptor subfamily 1 group H member 3, fatty acid binding protein 3 (FABP3), carnitine palmitoyltransferase II, acyl-Coenzyme A dehydrogenase long chain (ACADL), acyl-Coenzyme A oxidase 2 branched chain, and fatty acid binding protein 4, showed significant effects with regard to IMF and were differentially expressed between the low- and high-marbled groups (p<0.05). Analysis of the gene co-expression network based on Pearson's correlation coefficients identified 10 up-regulated genes in the high-marbled group that formed a major cluster. Among these genes, the PPARG-FABP4 gene pair exhibited the strongest correlation in the network. Glycerol kinase was found to play a role in mediating activation of the differentially expressed genes. We categorized the 10 significantly differentially expressed genes into the corresponding downstream pathways and investigated the direct interactive relationships among these genes. We suggest that fatty acid oxidation is the major downstream pathway affecting IMF content. The PPARG/RXRA complex triggers activation of target genes involved in fatty acid oxidation resulting in increased triglyceride formation by ATP production. Our findings highlight candidate genes associated with the IMF content of the loin muscle of Korean cattle and provide insight into the biological mechanisms that determine adipose deposition within muscle.