PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty‐acid metabolic enzymes

Seo, Yeon Seok; Kim, Ji Hoon; Jo, Nam Young; Choi, Kyung Mook; Baik, Sei Hyun; Park, Jong Jae; Kim, Jae Seon; Byun, Kwan Soo; Bak, Young Tae; Lee, Chang Hong; Kim, Ae Ree; Yeon, Jong Eun

doi:10.1111/j.1440-1746.2006.04819.x

Cited by 135 publications

(95 citation statements)

References 42 publications

(85 reference statements)

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“…It was suggested that PPARα activation by fenofibrate enhances hepatic FA turnover. Namely, it increased mRNA expression of FA β-oxidation enzymes in obese rats with T2DM [76] . These include FA transport protein, FA binding protein, carnitine palmitoyltransferase II, as well as medium-and longchain acyl-CoA dehydrogenase and acyl-CoA oxidase [76,77] .…”

Section: Mechanistic Implicationsmentioning

confidence: 99%

“…Namely, it increased mRNA expression of FA β-oxidation enzymes in obese rats with T2DM [76] . These include FA transport protein, FA binding protein, carnitine palmitoyltransferase II, as well as medium-and longchain acyl-CoA dehydrogenase and acyl-CoA oxidase [76,77] . A high-fat diet-associated increase in the liver inflammatory gene expression may be ameliorated by fenofibrate [74] .…”

Section: Mechanistic Implicationsmentioning

confidence: 99%

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Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

131

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Non-alcoholic fatty liver disease (NAFLD) is a common health problem with a high mortality burden due to its liver-and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). Impaired hepatic fatty acid (FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors (PPARs) are involved in lipid and glucose metabolic pathways. The novel concept is that the activation of the PPARα subunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis. These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet, T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent. In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

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Section: Mechanistic Implicationsmentioning

confidence: 99%

Section: Mechanistic Implicationsmentioning

confidence: 99%

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

131

View full text Add to dashboard Cite

show abstract

“…So, as a TNF-a blocker, pentoxifylline improves both steatosis and inflammation in patients with NAFLD and NASH (64)(65)(66). Antioxidants showed modest improvement in steatosis and lobular inflammation, with no effect on body weight, waist circumference, LDL-cholesterol, and fibrosis (48,67).…”

Section: Therapy Of Nafld and Nashmentioning

confidence: 99%

Nonalcoholic fatty liver disease: Diagnosis, pathogenesis, and management

Başaranoğlu

Örmeci²

2014

Turk J Gastroenterol

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Nonalcoholic fatty liver disease (NAFLD) is an umbrella term that covers both a relatively benign condition, which is simple steatosis, and nonalcoholic steatohepatitis (NASH). NASH is characterized by a chronic and progressive liver pathology that may progress to cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver transplantation. Despite the growing body of evidence, one of the important and unresolved problems is the pathogenesis of NASH. It might be a metabolic disturbance as a primary abnormality in NAFLD. Insulin resistance is at the center of these metabolic abnormalities. Then, hepatocyte injury might be induced by oxidative stress. This ongoing process progresses to NASH, even to cirrhosis in some patients. In addition to oxidative stress, possibilities for the next hit are lipid peroxidation, reactive metabolites, adipose tissue products, transforming growth factor-b 1 , Fas ligand, mitochondrial dysfunction, respiratory chain deficiency, and intestinal microbiota. Currently, there is no well-established and approved therapy. Recommendations are to improve existing co-morbidities, such as obesity, hyperlipidemia, or type 2 diabetes, and lifestyle modification with weight loss and exercise.

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“…Fenofibrate, a PPARα agonist, can specifically bind to PPARα and activate expression of numerous genes participating in fatty acid oxidation, control of triglycerides and cholesterol metabolism (9,10). Fenofibrate, therefore, was very effective to the nonalcoholic fatty liver diseases by modulating lipid metabolic enzymes such as fatty acid transport protein, fatty acid binding protein, long chain acyl-CoA dehydrogenase and acyl-CoA oxidase (11). The abdominal and skeletal adiposity in the diabetic rats was greatly improved by treatment with fenofibrate (4).…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of fat and muscle proteins in fenofibratefed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein

Hahm

Ahn²,

Noh³

et al. 2010

BMB Reports

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Fenofibrate, an agonist of PPARα, plays an important role in activating many proteins catalyzing lipid metabolism, and it also has a considerable effect on improvement of insulin sensitivity in the diabetic condition. To investigate fenofibratedependent expression of peripheral tissue proteins in diabetes, we analyzed whole muscle or fat proteins of fenofibrate-fed OLETF rats, an animal model of type II diabetes, using 2-dimensional gel electrophoresis. We found that many proteins were specifically expressed in a fenofibrate-dependent manner in these diabetic rats. In particular, a functionally unknown C11orf59 protein was differentially expressed in the muscle tissues (about 5-fold increase) in fenofibrate-fed OLETF rats as compared to control rats. Additionally, the signal proteins phosphatidylethanolamine binding protein and IkB interacting protein were differentially regulated in the fenofibrate-treated adipose tissues. We suggest here that these proteins might be involved in controlling lipid or carbohydrate metabolism in diabetes via PPARα activation. [BMB reports 2010; 43(5): 337-343]

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PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty‐acid metabolic enzymes

Cited by 135 publications

References 42 publications

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease: Diagnosis, pathogenesis, and management

Comparative analysis of fat and muscle proteins in fenofibratefed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein

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