Regulation of lipid metabolism and gene expression by fenofibrate in hamsters

Guo, Qiu; Wang, Pei-Ran; Milot, Denise P.; Ippolito, Marc C.; Hernandez, Melba; Burton, Charlotte; Wright, Samuel D.; Chao, Yu‐Sheng

doi:10.1016/s1388-1981(01)00156-1

Cited by 55 publications

(34 citation statements)

References 69 publications

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“…53 Previous studies have also described upregulation of some but not all of the genes of lipid metabolism shown in Table 1 and Figure 3, including triglyceride lipolysis, 5,6 FA transport 54,55 and b-oxidation. 11,12,[56][57][58] In agreement with previous studies, 58 we did not find significant changes in the lipogenic genes in response to fenofibrate treatment. The upregulation of both Scd-1, which has been observed previously, 59 and Elovl3 suggest that fibrates may promote synthesis of unsaturated FA and long-chain FA.…”

Section: Discussionsupporting

confidence: 93%

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

et al. 2009

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We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and b-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.

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Section: Discussionsupporting

confidence: 93%

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

et al. 2009

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“…All these gene expression levels in liver were found to be reduced in rohitukine-treated groups compared with the HFD-treated group ( Fig. 5H ), similar to that observed with fenofi brate, the standard antidyslipidemic agent ( 66 ). In adipocytes, 10 days of HFD intervention showed adipocyte hypertrophy as well as epididymal weight gain, which was reduced in the rohitukine-treated group.…”

Section: Discussionsupporting

confidence: 79%

Rohitukine inhibits in vitro adipogenesis arresting mitotic clonal expansion and improves dyslipidemia in vivo

Varshney

Shankar

Beg

et al. 2014

Journal of Lipid Research

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“…While the relative contributions of AMPK activation and ACL inhibition in vivo are not addressed in these studies, the robust effects of ETC-1002 hepatic steatosis (27)(28)(29)(30)(31)(32). To determine whether ETC-1002 benefi cially affects tissue and plasma parameters associated with dyslipidemia, HFHC-fed hamsters were treated for three weeks with ETC-1002 (30 mg/kg/day).…”

Section: Etc-1002 Corrects Dyslipidemia In Golden Syrian Hamsters Andmentioning

confidence: 99%

AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism

Pinkosky

Filippov

Srivastava

et al. 2013

Journal of Lipid Research

197

153

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This article is available online at http://www.jlr.org Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality in the Western world ( 1 ). Elevated levels of LDL-cholesterol (LDL-C) have consistently shown a positive association with the development of CVD, justifying the current therapeutic strategies to prevent CVD primarily by the use of statins. Members of this drug class inhibit HMG-CoA reductase (HMGR), the rate-limiting enzyme for de novo cholesterol synthesis, thereby leading to decreased LDL-C ( 2-4 ). While the benefi ts of statins have been documented ( 2 ), many individuals on statin therapy still remain at a higher risk of developing CVD. It is possible this residual risk is a result of other metabolic syndrome (MetS) risk factors characterized by dyslipidemia and insulin resistance and is also in part due to statin intolerance ( 5-7 ) and noncompliance often related to statininduced myalgia ( 8, 9 ). Statins are effective at decreasing LDL-C and CVD; however, frequent muscle-related side effects limit dosage and impede maximal risk reduction in dyslipidemic patients ( 10 ). Furthermore, recent evidence suggests that high-dose statins may increase the risk of developing type 2 diabetes (T2D) ( 11 ), further justifying the need for alternative therapeutic interventions that have statin-like effects for lowering LDL-C and are designed to Abstract ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel investigational drug being developed for the treatment of dyslipidemia and other cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose-lowering properties of ETC-1002, characterized in preclinical disease models, are believed to be due to dual inhibition of sterol and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid ␤ -oxidation. However, the molecular mechanism(s) mediating these activities remained undefi ned.

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Regulation of lipid metabolism and gene expression by fenofibrate in hamsters

Cited by 55 publications

References 69 publications

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

Rohitukine inhibits in vitro adipogenesis arresting mitotic clonal expansion and improves dyslipidemia in vivo

AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism

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