Highly sensitive upregulation of apolipoprotein A-IV by peroxisome proliferator-activated receptor α (PPARα) agonist in human hepatoma cells

Nagasawa, Michiaki; Akasaka, Yunike; Ide, Tomohiro; Hara, Tomoko; Kobayashi, Naoki; Utsumi, Mari; Murakami, Koji

doi:10.1016/j.bcp.2007.08.020

Cited by 21 publications

(21 citation statements)

References 43 publications

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“…Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator in hepatic lipid metabolism, and apoA-IV had been identified as a potential therapeutic target for dyslipidaemia [30]. Oral administration of PPARα agonist KRP-101 in dogs caused a decrease in serum TG accompanied by an increase in serum apoA-IV levels [30].…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp

2010

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Tamarindus indicaL. (T. indica) or locally known as asam jawa belongs to the family of Leguminosae. The fruit pulp had been reported to have antioxidant activities and possess hypolipidaemic effects. In this study, we attempted to investigate the gene expression patterns in human hepatoma HepG2 cell line in response to treatment with low concentration of the fruit pulp extracts. Microarray analysis using Affymetrix Human Genome 1.0 S.T arrays was used in the study. Microarray data were validated using semi-quantitative RT–PCR and real-time RT–PCR. Amongst the significantly up-regulated genes were those that code for the metallothioneins (MT1M, MT1F, MT1X) and glutathione S-transferases (GSTA1, GSTA2, GST02) that are involved in stress response. APOA4, APOA5, ABCG5 and MTTP genes were also significantly regulated that could be linked to hypolipidaemic activities of the T. indica fruit pulp.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp

2010

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“…Administration of PPAR agonists in dogs, increased the serum levels of apoA-IV, indicating that upregulation of apoA-IV may be one of the key mechanisms underlying PPAR agonist-induced triacylglycerol decrease and HDL elevation [133].…”

Section: Apoa-ivmentioning

confidence: 99%

Recent Advances on the Antiatherogenic Effects of HDL-Derived Proteins and Mimetic Peptides

Petraki

Mantani²,

Tselepis³

2009

CPD

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The plasma levels of high-density lipoprotein (HDL) cholesterol are inversely correlated with the risk of atherosclerosis and cardiovascular disease (CVD) in humans. One of the major mechanisms whereby HDL particles protect against atherosclerosis is that of reverse cholesterol transport from atherosclerotic lesion macrophages to the liver. HDL particles also exhibit various antiatherogenic and cardioprotective effects by modulating the function of various cells including the cells of the artery wall and by expressing antioxidant, anti-inflammatory, antithrombotic and antiapoptotic effects. Most these effects are mediated by various lipid and protein HDL components. A plethora of studies have been conducted in order to shed light on the mechanisms by which each HDL component contributes to the functionality of this lipoprotein. The complete elucidation of these mechanisms will significantly contribute to current efforts focused on the development of therapeutic strategies to promote the antiatherogenic potency of HDL. The present review discusses current knowledge on the biological activities of the major apolipoproteins and enzymes associated with HDL, which may significantly contribute to the overall antiatherogenic and cardioprotective effects of this lipoprotein.

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“…This study investigated whether a highly potent and subtype-selective PPAR␣ agonist can suppress insulin resistance and obesity without affecting food intake in obese and insulin-resistant dogs. reported to be a potent and subtype-selective PPAR␣ agonist in a Gal4-transactivation assay using human PPAR subtypes (29). Fenofibric acid was purchased from Tyger Scientific (Ewing, NJ).…”

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confidence: 99%

A novel PPARα agonist ameliorates insulin resistance in dogs fed a high-fat diet

Tsunoda¹,

Kobayashi²,

Ide³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Tsunoda M, Kobayashi N, Ide T, Utsumi M, Nagasawa M, Murakami K. A novel PPAR␣ agonist ameliorates insulin resistance in dogs fed a high-fat diet. Am J Physiol Endocrinol Metab 294: E833-E840, 2008. First published January 22, 2008 doi:10.1152/ajpendo.00627.2007.-Agonism of peroxisome proliferator-activated receptor (PPAR) ␣, a key regulator of lipid metabolism, leads to amelioration of lipid abnormalities in dyslipidemic patients. However, whether PPAR␣ agonism is an effective form of therapy for obesity-related insulin resistance associated with lipid abnormalities is unclear. The present study investigated the effects of a potent and subtype-selective PPAR␣ agonist, KRP-101, in a nonrodent insulin-resistant animal model under pair-fed conditions. Beagle dogs were fed a high-fat diet for 24 wk to induce insulin resistance. During the final 12 wk, 0.03 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 KRP-101 (n ϭ 5) or vehicle (n ϭ 5) was administered orally once a day. KRP-101 administration resulted in a significantly lower weight of overall visceral fat, which is associated with increased adiponectin and decreased leptin in serum. KRP-101 administration improved hyperglycemia and hyperinsulinemia as well as dyslipidemia in dogs fed a high-fat diet. Oral glucose tolerance test showed that KRP-101 administration improved glucose intolerance. The KRP-101 group showed a markedly lower hepatic triglyceride concentration. Lipid oxidation was increased in the liver and skeletal muscles of the KRP-101 group. These findings in the dog model suggest that the use of potent and subtype-selective PPAR␣ agonists as a potentially relevant therapeutic approach to treat human insulin resistance associated with visceral obesity.

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Highly sensitive upregulation of apolipoprotein A-IV by peroxisome proliferator-activated receptor α (PPARα) agonist in human hepatoma cells

Cited by 21 publications

References 43 publications

Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp

Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp

Recent Advances on the Antiatherogenic Effects of HDL-Derived Proteins and Mimetic Peptides

A novel PPARα agonist ameliorates insulin resistance in dogs fed a high-fat diet

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