Document Detail

Prevention and reversal of obesity and glucose intolerance in mice by DHA derivatives.
MedLine Citation:
PMID:  19148125     Owner:  NLM     Status:  MEDLINE    
The n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert hypolipidemic effects and prevent development of obesity and insulin resistance in animals fed high-fat diets. We sought to determine the efficacy of alpha-substituted DHA derivatives as lipid-lowering, antiobesity, and antidiabetic agents. C57BL/6 mice were given a corn oil-based high-fat (35% weight/weight) diet (cHF), or cHF with 1.5% of lipids replaced with alpha-methyl DHA ethyl ester (Substance 1), alpha-ethyl DHA ethyl ester (Substance 2), alpha,alpha-di-methyl DHA ethyl ester (Substance 3), or alpha-thioethyl DHA ethyl ester (Substance 4) for 4 months. Plasma markers of glucose and lipid metabolism, glucose tolerance, morphology, tissue lipid content, and gene regulation were characterized. The cHF induced obesity, hyperlipidemia, impairment of glucose homeostasis, and adipose tissue inflammation. Except for Substance 3, all other substances prevented weight gain and Substance 2 exerted the strongest effect (63% of cHF-controls). Glucose intolerance was significantly prevented (~67% of cHF) by both Substance 1 and Substance 2. Moreover, Substance 2 lowered fasting glycemia, plasma insulin, triacylglycerols, and nonesterified fatty acids (73, 9, 47, and 81% of cHF-controls, respectively). Substance 2 reduced accumulation of lipids in liver and skeletal muscle, as well as adipose tissue inflammation associated with obesity. Substance 2 also induced weight loss in dietary obese mice. In contrast to DHA administered either alone or as a component of the EPA/DHA concentrate (replacing 15% of dietary lipids), Substance 2 also reversed established glucose intolerance in obese mice. Thus, Substance 2 represents a novel compound with a promising potential in the treatment of obesity and associated metabolic disturbances.
Martin Rossmeisl; Tomas Jelenik; Zuzana Jilkova; Kristyna Slamova; Vladimir Kus; Michal Hensler; Dasa Medrikova; Ctibor Povysil; Pavel Flachs; Vidya Mohamed-Ali; Morten Bryhn; Kjetil Berge; Anne K Holmeide; Jan Kopecky
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-15
Journal Detail:
Title:  Obesity (Silver Spring, Md.)     Volume:  17     ISSN:  1930-7381     ISO Abbreviation:  Obesity (Silver Spring)     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-27     Completed Date:  2009-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101264860     Medline TA:  Obesity (Silver Spring)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1023-31     Citation Subset:  IM    
Department of Adipose Tissue Biology and Center for Applied Genomics, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
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MeSH Terms
Antilipemic Agents / therapeutic use
Dietary Fats
Disease Models, Animal
Docosahexaenoic Acids / therapeutic use*
Energy Intake
Glucose / metabolism
Glucose Intolerance / drug therapy*,  prevention & control
Glucose Tolerance Test
Mice, Inbred C57BL
Obesity / drug therapy*,  prevention & control
Polymerase Chain Reaction
RNA / genetics,  isolation & purification
Triglycerides / metabolism
Weight Gain
Reg. No./Substance:
0/Antilipemic Agents; 0/Dietary Fats; 0/Triglycerides; 25167-62-8/Docosahexaenoic Acids; 50-99-7/Glucose; 63231-63-0/RNA

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

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