An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides. / Grevengoed, Trisha J; Trammell, Samuel A J; Svenningsen, Jens S; Makarov, Mikhail; Nielsen, Thomas Svava; Jacobsen, Jens C B; Calder, Philip C.; Migaud, Marie E; Cravatt, Benjamin; Gillum, Matthew P.

In: Journal of Clinical Investigation, Vol. 131, No. 6, e143861, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Grevengoed, TJ, Trammell, SAJ, Svenningsen, JS, Makarov, M, Nielsen, TS, Jacobsen, JCB, Calder, PC, Migaud, ME, Cravatt, B & Gillum, MP 2021, 'An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides', Journal of Clinical Investigation, vol. 131, no. 6, e143861. https://doi.org/10.1172/JCI143861

APA

Grevengoed, T. J., Trammell, S. A. J., Svenningsen, J. S., Makarov, M., Nielsen, T. S., Jacobsen, J. C. B., Calder, P. C., Migaud, M. E., Cravatt, B., & Gillum, M. P. (2021). An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides. Journal of Clinical Investigation, 131(6), [e143861]. https://doi.org/10.1172/JCI143861

Vancouver

Grevengoed TJ, Trammell SAJ, Svenningsen JS, Makarov M, Nielsen TS, Jacobsen JCB et al. An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides. Journal of Clinical Investigation. 2021;131(6). e143861. https://doi.org/10.1172/JCI143861

Author

Grevengoed, Trisha J ; Trammell, Samuel A J ; Svenningsen, Jens S ; Makarov, Mikhail ; Nielsen, Thomas Svava ; Jacobsen, Jens C B ; Calder, Philip C. ; Migaud, Marie E ; Cravatt, Benjamin ; Gillum, Matthew P. / An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides. In: Journal of Clinical Investigation. 2021 ; Vol. 131, No. 6.

Bibtex

@article{990a5f59740f4607aa0cb5f8cb17138d,
title = "An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides",
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 (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, while 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 was a negative feedback mediator that limited 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.",
author = "Grevengoed, {Trisha J} and Trammell, {Samuel A J} and Svenningsen, {Jens S} and Mikhail Makarov and Nielsen, {Thomas Svava} and Jacobsen, {Jens C B} and Calder, {Philip C.} and Migaud, {Marie E} and Benjamin Cravatt and Gillum, {Matthew P}",
year = "2021",
doi = "10.1172/JCI143861",
language = "English",
volume = "131",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "6",

}

RIS

TY - JOUR

T1 - An abundant biliary fatty acid metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides

AU - Grevengoed, Trisha J

AU - Trammell, Samuel A J

AU - Svenningsen, Jens S

AU - Makarov, Mikhail

AU - Nielsen, Thomas Svava

AU - Jacobsen, Jens C B

AU - Calder, Philip C.

AU - Migaud, Marie E

AU - Cravatt, Benjamin

AU - Gillum, Matthew P

PY - 2021

Y1 - 2021

N2 - 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 (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, while 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 was a negative feedback mediator that limited 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.

AB - 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 (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, while 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 was a negative feedback mediator that limited 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.

U2 - 10.1172/JCI143861

DO - 10.1172/JCI143861

M3 - Journal article

C2 - 33507883

VL - 131

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

M1 - e143861

ER -

ID: 256168997