An abundant biliary metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides.
J Clin Invest
; 131(6)2021 03 15.
Article
em En
| MEDLINE
| ID: mdl-33507883
ABSTRACT
Omega-3 fatty acids from fish oil reduce triglyceride levels in mammals, yet the mechanisms underlying this effect have not been fully clarified, despite the clinical use of omega-3 ethyl esters to treat severe hypertriglyceridemia and reduce cardiovascular disease risk in humans. Here, we identified in bile a class of hypotriglyceridemic omega-3 fatty acid-derived N-acyl taurines (NATs) that, after dietary omega-3 fatty acid supplementation, increased to concentrations similar to those of steroidal bile acids. The biliary docosahexaenoic acid-containing (DHA-containing) NAT C226 NAT was increased in human and mouse plasma after dietary omega-3 fatty acid supplementation and potently inhibited intestinal triacylglycerol hydrolysis and lipid absorption. Supporting this observation, genetic elevation of endogenous NAT levels in mice impaired lipid absorption, whereas selective augmentation of C226 NAT levels protected against hypertriglyceridemia and fatty liver. When administered pharmacologically, C226 NAT accumulated in bile and reduced high-fat diet-induced, but not sucrose-induced, hepatic lipid accumulation in mice, suggesting that C226 NAT is a negative feedback mediator that limits excess intestinal lipid absorption. Thus, biliary omega-3 NATs may contribute to the hypotriglyceridemic mechanism of action of fish oil and could influence the design of more potent omega-3 fatty acid-based therapeutics.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
Base de dados:
MEDLINE
Assunto principal:
Triglicerídeos
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Hipertrigliceridemia
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Ácidos Graxos Ômega-3
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2021
Tipo de documento:
Article