Prevention and reversal of obesity and glucose intolerance in mice by DHA derivatives
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
19148125
DOI
10.1038/oby.2008.602
PII: oby2008602
Knihovny.cz E-zdroje
- MeSH
- dietní tuky MeSH
- energetický příjem MeSH
- glukosa metabolismus MeSH
- glukózový toleranční test MeSH
- hmotnostní přírůstek MeSH
- hypolipidemika terapeutické užití MeSH
- kyseliny dokosahexaenové terapeutické užití MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- obezita farmakoterapie prevence a kontrola MeSH
- polymerázová řetězová reakce MeSH
- porucha glukózové tolerance farmakoterapie prevence a kontrola MeSH
- RNA genetika izolace a purifikace MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dietní tuky MeSH
- glukosa MeSH
- hypolipidemika MeSH
- kyseliny dokosahexaenové MeSH
- RNA MeSH
- triglyceridy MeSH
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.
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