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Potent PPAR? activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

ABSTRACT: Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor ? (PPAR?) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPAR? agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPAR? agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPAR? activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPAR? activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPAR? agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.

SUBMITTER: Kim YI

PROVIDER: S-EPMC3276502 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

Kim Young-il YI Hirai Shizuka S Goto Tsuyoshi T Ohyane Chie C Takahashi Haruya H Tsugane Taneaki T Konishi Chiaki C Fujii Takashi T Inai Shuji S Iijima Yoko Y Aoki Koh K Shibata Daisuke D Takahashi Nobuyuki N Kawada Teruo T

PloS one 20120209 2

Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present onl ...[more]

PMID: 22347463

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Project description:Background: Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by pediatric obesity is a common but scarcely understood aspect of the disease. Peroxisome proliferator-activated receptors (PPARs) are a group of transcription factors essential for energy and immune homeostasis of different tissues. Besides, the glucagon-like peptide-1 receptor (GLP-1R) activation influences insulin secretion, but also regulates the cytokine profile possibly mediated through a PPAR isotype. However, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients remains unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R in leukocytes, and its correlation with metabolic, hormonal, inflammatory, and anthropometric markers in an obese pediatric population.Results: Obese children and adolescents presented a significant increase in anthropometric and body composition parameters, TG, VLDL, TG/HDL, android fat (%)/gynoid fat (%) (A/G%) index, and HOMA score when compared with the control group. Obese participants exhibited a pro-inflammatory profile with an augment of IL-8 (p?=?0,0081), IL-6 (p?=?0,0005), TNF-? (p?=?0,0004), IFN-? (p?=?0,0110), MCP-1 (p?=?0,0452), and adipsin (p?=?0,0397), whereas displayed a reduction of adiponectin (p?=?0,0452). The expression of PPAR? and GLP-1R was lower in the leukocytes from obese participants than in lean subjects. Furthermore, PPAR? correlates negatively with TNF-? (p?=?0,0383), while GLP-1R did not show correlation with any inflammatory variable. However, both receptors correlate negatively with the abdominal skinfold. Although PPAR?/? expression was similar between groups, it was negatively associated with IL-8 levels (p?=?0,0085).Conclusions: PPAR? and PPAR?/? expression are negatively correlated with the proinflammatory markers TNF-? and IL-8, respectively, suggesting participation in the regulation of inflammation which was observed to be altered in pediatric obesity. Furthermore, PPAR? and GLP-1R are downregulated in leukocytes from obese participants. The low expression of both receptors is correlated with an increase in abdominal skinfold, suggesting a role in fat distribution that could indirectly affect cytokine secretion from different immune and adipose cells, likely triggering an inflammatory profile as a consequence of obesity. Altogether, these findings may impact the understanding and implementation of PPAR? or GLP-1R agonists in the clinic.

Dataset Information

Potent PPAR? activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

Publications

Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

Similar Datasets

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