Fenofibrate lowers lipid accumulation in myotubes by modulating the PPARα/AMPK/FoxO1/ATGL pathway

Chen, Wei Lu; Chen, Yu Lin; Chiang, Yu Ming; Wang, Shyang Guang; Lee, Horng Mo

doi:10.1016/j.bcp.2012.05.022

Cited by 69 publications

(49 citation statements)

References 33 publications

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“…The present study clearly showed that three fibrates, fenofibrate, bezafibrate, and clofibric acid, reduced the hepatic concentration of TAG in dose-and time-dependent manners, although conflicting results appear in the literature concerning the effects of fenofibrate on hepatic TAG content (11,24). In the current study, fenofibrate behaved as the most powerful hepatic TAG suppressor, while clofibric acid was the least potent.…”

Section: Discussionsupporting

confidence: 42%

Fibrates Reduce Triacylglycerol Content by Upregulating Adipose Triglyceride Lipase in the Liver of Rats

Karahashi¹,

Hoshina²,

Yamazaki³

et al. 2013

J Pharmacol Sci

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Abstract. Hepatic triacylglycerol (TAG) homeostasis is maintained by carefully regulated balance between its synthesis and disposal. Impairment in this balance causes steatosis. The aims of this study were i) to uncover whether fibrates control TAG concentration through the action of adipose triglyceride lipase (ATGL) and ii) to compare the potency of the effects on ATGL expression and TAG concentration among fenofibrate, bezafibrate, and clofibric acid in the liver of rats. Treatments of rats with the three fibrates induced ATGL and concomitantly decreased hepatic TAG concentration. The upregulation of ATGL was likely mediated through the activation of peroxisome proliferator-activated receptor a. Fibrates also expanded capacity of fatty acid b-oxidation. Importantly, three fibric acids (fenofibric, bezafibric, and clofibric acids) that are active metabolites formed in the liver exhibited almost the same potency to elevate ATGL expression in vivo, despite the fact that there were considerable differences in this regard among fenofibrate, bezafibrate, and clofibric acid when compared on the basis of their dosage. These results suggest that ATGL represents a potential therapeutic target for ameliorating hepatic steatosis and that fibric acids are promising agents to ameliorate and/or protect against hepatic steatosis.

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Section: Discussionsupporting

confidence: 42%

Fibrates Reduce Triacylglycerol Content by Upregulating Adipose Triglyceride Lipase in the Liver of Rats

Karahashi¹,

Hoshina²,

Yamazaki³

et al. 2013

J Pharmacol Sci

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“…It has been shown that ATGL is downregulated in mouse models of obesity (Villena et al, 2004). Present study showed that dietary supplement of Garcinia Cambogia extracts has no affected on the ACO mRNA level in rats fed high- (Chen et al, 2012). Present study found that AMPKα2 mRNA levels tend to increased, and AMPKα1 mRNA levels were significantly increased in rats under high-fat diet treated with low and high dose of Garcinia Cambogia extracts.…”

Section: Numerous Studies Have Shown An Association Between Garciniamentioning

confidence: 52%

<i>Garcinia Cambogia</i> Extracts Prevented Fat Accumulation via Adiponectin-AMPK Signaling Pathway in Developing Obesity Rats

Liu

Han

et al. 2015

FSTR

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AbbreviationsACL, ATP-citrate lyase; ACO, Acyl-CoA oxidase; AdipoR1, adiponectin receptor 1; AdipoR2, adiponectin receptor 2; AMPK, adenosine 5'-monophosphate-actvated protein kinase; ATGL, adipose triglyceride lipase; BMI, body mass index; CPT-I, carnitine palmitoyltransferase-I; FAS, fatty acid synthesis; HCA, hydroxycitric acid; HDL, high-density lipoprotein; HL, hepatic lipase; NEFA, nonesterified fatty acid; TC, total cholesterol; TG, triglycerol. Original paper Garcinia Cambogia Extracts Prevented Fat Accumulation via Adiponectin- AMPK Signaling Pathway in Developing Obesity RatsGuanxing Liu, Ningning Han, Jing Han, Di CHen, Jian Kang and Haitian Ma IntroductionObesity is a public health problem which is fast growing throughout the modern world. It is a serious risk factor for so-called lifestyle-related diseases such as diabetes, cardiovascular disease and hypertension (Jebb and Moore, 1999;Nakamura et al., 1994). In addition to exercise, it is well known that anti-obesity foods and food ingredients could control and reduce body weight. Some herbal products and plant extracts, such as Semen Cassiaem (Junbao et al., 2004), Panax ginseng berry extract (Attele et al., 2002), Singiber officinale Roscoe (Hasegawa, 2001), and Platycodi radix (Han et al., 2000) have been shown to exert anti-obesity effects in rodents with high fat diet induced obesity (Kim et al., 2007).Garcinia cambogia is an edible fruit native to Southeast Asia (Saito et al., 2005). Its dried rind has been used for centuries throughout Southeast Asia as a food preservative, flavoring agent and carminative. Also, Garcinia cambogia extracts has been used as an ingredient of dietary supplements for weight loss.(-)-Hydroxycitric acid (HCA), a primary acid and the major active G. Liu et al. 836 ingredient in the fruit rinds of Garcinia Cambogia (Lewis and Neelakantan, 1965), has been shown to suppress appetite, body weight gain and fat accumulation in both experimental animals and humans (Greenwood et al., 1981;Heymsfield et al., 1998;Ohia, 2002;Rao and Sakariah, 1988;Sullivan et al., 1974;. HCA had been identified as a potent competitive inhibitor of the extra-mitochondrial enzyme adenosine triphosphate-citratelyase (Watson and Lowenstein, 1970), which catalyzes the cleavage of citrate in extra-mitochondrial to oxaloacetate and acetyl-CoA, a building block of fatty acids synthesis (Márquez, 2012). The inhibitory action of HCA induces the reduction of acetyl-CoA content, thus limiting the biosynthesis of fatty acids and cholesterol (Lowenstein, 1971;Sullivan et al., 1974). Also, the reduction of acetyl-CoA content could decrease the concentration of malonyl-CoA, which stimulates carnitine palmitoyltransferase I (CPT-1) activity and fatty acid oxidation (Ishihara et al., 2000;McCarty, 1994;Saha et al., 1999). Although some studies had revealed that HCA may suppress de novo fatty acid biosynthesis and appetite (Kovacs and Westerterp-Plantenga, 2006) and increase energy expenditure (Kim et al., 2008), subsequently reducing fat accumulation and b...

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“…In addition, as a transcription factor, FoxO1 acts at a convergence point of several growth factor receptor tyrosine kinase pathways that may play central roles in glioma tumorigenesis [16,17]. In a previous study, Chen et al found that FF-induced lipid-lowering effects were associated with increased expression of FoxO1 in myotubes [27]. Our study provides a direct link between FF treatment and FoxO1 nuclear accumulation, which in turn increases the amount of a FoxO1-dependent cell cycle-related protein, p27 kip [15].…”

Section: Discussionmentioning

confidence: 96%

Fenofibrate induces G0/G1 phase arrest by modulating the PPARα/FoxO1/p27kip pathway in human glioblastoma cells

et al. 2015

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Fenofibrate, a fibric acid derivative, is known to possess lipid-lowering effects. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcriptional activity has been reported to exhibit anticancer effects, the underlying mechanisms are poorly understood. In this study, we investigated the mechanisms behind the antiproliferative effects of fenofibrate in U87MG cells (human glioma cell line) using the WST-8 Cell Proliferation Assay Kit. Furthermore, we examined genome-wide gene expression profiles and molecular networks using the DAVID online software. Fenofibrate reduced the expression of 405 genes and increased the expression of 2280 genes. DAVID analysis suggested that fenofibrate significantly affected cell cycle progression and pathways involved in cancer, including the mTOR signaling pathway and insulin signaling pathway. Results of flow cytometry analysis indicated that fenofibrate induced cell cycle G0/G1 arrest in U87MG cells. Furthermore, we identified the FoxO1-p27(kip) signaling axis to be involved in fenofibrate-induced cell cycle arrest. Our findings suggest that in addition to its known lipid-lowering effects, fenofibrate may be used as an antitumor agent in glioma therapy.

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Fenofibrate lowers lipid accumulation in myotubes by modulating the PPARα/AMPK/FoxO1/ATGL pathway

Cited by 69 publications

References 33 publications

Fibrates Reduce Triacylglycerol Content by Upregulating Adipose Triglyceride Lipase in the Liver of Rats

Fibrates Reduce Triacylglycerol Content by Upregulating Adipose Triglyceride Lipase in the Liver of Rats

<i>Garcinia Cambogia</i> Extracts Prevented Fat Accumulation via Adiponectin-AMPK Signaling Pathway in Developing Obesity Rats

Fenofibrate induces G0/G1 phase arrest by modulating the PPARα/FoxO1/p27kip pathway in human glioblastoma cells

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