Document Detail

Comparative study between the effect of the peroxisome proliferator activated receptor-alpha ligands fenofibrate and n-3 polyunsaturated fatty acids on activation of 5'-AMP-activated protein kinase-alpha1 in high-fat fed rats.
MedLine Citation:
PMID:  19814866     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Obesity is a risk factor for type 2 diabetes mellitus. It results from an energy imbalance in which energy intake exceeds energy expenditure. The cellular fuel gauge 5'-AMP-activated protein kinase (AMPK) is a heterotrimeric protein consisting of one catalytic subunit (alpha) and two non-catalytic subunits (beta and gamma), and approximately equal levels of alpha1 and alpha2 complexes are present in the liver. AMPK regulates metabolic pathways in response to metabolic stress and in particular ATP depletion to switch on energy-producing catabolic pathways such as beta-oxidation of fatty acids and switch off energy-depleting processes such as synthesis of fatty acid and cholesterol. A high-fat diet alters AMPK-alpha1 gene expression in the liver and skeletal muscle of rats and results in body weight gain and hyperglycaemia. The aim of this study was to investigate and compare the potential effects of peroxisome proliferator-activated receptor (PPAR)-alpha agonists fenofibrate and n-3 polyunsaturated fatty acids (PUFAs) in modulation of AMPK-alpha1 activity in liver and skeletal muscle of high-fat diet fed rats.
METHODS: Reverse transcription-polymerase chain reaction was used for determination of AMPK-alpha1 in liver and soleus muscle and both PPAR-alpha and CPT-1 in hepatic tissues. Serum, total cholesterol, triacylglycerol, fatty acid and fasting blood glucose were determined colorimetrically.
KEY FINDINGS: Both PPAR-alpha agonists, fenofibrate and n-3 PUFA, increased the mRNA expression of AMPK-alpha1 activity in liver and skeletal muscle of obese diabetic rats. Fenofibrate was superior in its activation of hepatic mRNA expression of AMPK-alpha 1 to exert more lipolytic effect and body weight reduction, as estimated through the decrease of triacylglycerol output and serum levels of fatty acid on the one hand and the increase in CPT-1 mRNA expression, the key enzyme in beta-oxidation of fatty acid, on the other hand. n-3 PUFA activated AMPK-alpha1 mRNA expression in skeletal muscle much more than fenofibrate to reveal more hypoglycaemic effect.
CONCLUSIONS: The PPAR-alpha agonists fenofibrate and n-3 PUFA could efficiently activate AMPK-alpha1 mRNA expression in liver and skeletal muscle to exert body weight reduction and hypoglycaemic effect, respectively.
Tarek M Kamal Motawi; Reem M Hashem; Laila A Rashed; Sabry M Abd El-Razek
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  61     ISSN:  2042-7158     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-09     Completed Date:  2010-01-21     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1339-46     Citation Subset:  IM    
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Egypt.
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MeSH Terms
AMP-Activated Protein Kinases / genetics,  metabolism*
Blood Glucose / drug effects
Body Weight / drug effects
Carnitine O-Palmitoyltransferase / genetics,  metabolism
Cholesterol / blood
Fatty Acids, Unsaturated / blood,  pharmacology*
Fenofibrate / pharmacology*
Food, Formulated
Gene Expression
Liver / drug effects,  metabolism
Muscle, Skeletal / drug effects,  metabolism
Obesity / blood,  genetics,  metabolism*
PPAR alpha / agonists*,  genetics,  metabolism
RNA, Messenger / metabolism
Random Allocation
Rats, Wistar
Triglycerides / blood
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids, Unsaturated; 0/PPAR alpha; 0/RNA, Messenger; 0/Triglycerides; 49562-28-9/Fenofibrate; 57-88-5/Cholesterol; EC O-Palmitoyltransferase; EC Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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