期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 131, 期 6, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI143861
关键词
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资金
- Novo Nordisk Foundation Center for Basic Metabolic Research
- Novo Nordisk Foundation [NNF18CC003490]
- Mitchell Cancer Institute.
- NIH [DA033760]
The study identified a class of hypotriglyceridemic omega-3 fatty acid-derived N-acyl taurines (NATs) in bile that can inhibit intestinal triacylglycerol hydrolysis and lipid absorption, preventing hypertriglyceridemia and fatty liver. These omega-3 NATs may contribute to the mechanism of action of fish oil and influence the design of more potent omega-3 fatty acid-based therapeutics.
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 C22:6 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 C22:6 NAT levels protected against hypertriglyceridemia and fatty liver. When administered pharmacologically, C22:6 NAT accumulated in bile and reduced high-fat diet-induced, but not sucrose induced, hepatic lipid accumulation in mice, suggesting that C22:6 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.
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