Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance.
Adipose Tissue
Adult
Aged
Cross-Sectional Studies
Diabetes Mellitus, Type 2
/ metabolism
Fatty Acids
/ metabolism
Female
Humans
Insulin Resistance
/ physiology
Lipids
Lipogenesis
/ physiology
Liver
/ diagnostic imaging
Male
Middle Aged
Non-alcoholic Fatty Liver Disease
/ metabolism
Triglycerides
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
22
08
2019
accepted:
20
03
2020
entrez:
22
4
2020
pubmed:
22
4
2020
medline:
5
8
2020
Statut:
epublish
Résumé
Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (
Identifiants
pubmed: 32312974
doi: 10.1038/s41467-020-15684-0
pii: 10.1038/s41467-020-15684-0
pmc: PMC7170906
doi:
Substances chimiques
Fatty Acids
0
Lipids
0
Triglycerides
0
Banques de données
ClinicalTrials.gov
['NCT03211299']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1891Références
Sayiner, M., Koenig, A., Henry, L. & Younossi, Z. M. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in the United States and the rest of the world. Clin. Liver Dis. 20, 205–214 (2016).
doi: 10.1016/j.cld.2015.10.001
Gaggini, M. et al. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 5, 1544–1560 (2013).
doi: 10.3390/nu5051544
Calzadilla Bertot, L. & Adams, L. A. The natural course of non-alcoholic fatty liver disease. Int. J. Mol. Sci. 17, 774 (2016).
doi: 10.3390/ijms17050774
Mantovani, A., Byrne, C. D., Bonora, E. & Targher, G. Nonalcoholic fatty liver disease and risk of incident Type 2 diabetes: a meta-analysis. Diabetes Care 41, 372–382 (2018).
doi: 10.2337/dc17-1902
Targher, G., Byrne, C. D., Lonardo, A., Zoppini, G. & Barbui, C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J. Hepatol. 65, 589–600 (2016).
doi: 10.1016/j.jhep.2016.05.013
Lim, S., Oh, T. J. & Koh, K. K. Mechanistic link between nonalcoholic fatty liver disease and cardiometabolic disorders. Int. J. Cardiol. 201, 408–414 (2015).
doi: 10.1016/j.ijcard.2015.08.107
Targher, G. & Byrne, C. D. Clinical review: nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J. Clin. Endocrinol. Metab. 98, 483–495 (2013).
doi: 10.1210/jc.2012-3093
Targher, G., Day, C. P. & Bonora, E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N. Engl. J. Med. 363, 1341–1350 (2010).
doi: 10.1056/NEJMra0912063
Brouwers, B. et al. Metabolic disturbances of non-alcoholic fatty liver resemble the alterations typical for type 2 diabetes. Clin. Sci. (Lond., Engl.: 1979) 131, 1905–1917 (2017).
doi: 10.1042/CS20170261
Matikainen, N. et al. Hepatic lipogenesis and a marker of hepatic lipid oxidation, predict postprandial responses of triglyceride-rich lipoproteins. Obesity (Silver Spring, Md.) 22, 1854–1859 (2014).
doi: 10.1002/oby.20781
Lambert, J. E., Ramos-Roman, M. A., Browning, J. D. & Parks, E. J. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 146, 726–735 (2014).
doi: 10.1053/j.gastro.2013.11.049
Gluchowski, N. L. et al. Hepatocyte deletion of triglyceride-synthesis enzyme acyl CoA: diacylglycerol acyltransferase 2 reduces steatosis without increasing inflammation or fibrosis in mice. Hepatology (Baltimore, Md.), 70, 1972–1985 (2019).
doi: 10.1002/hep.30765
Benhamed, F. et al. The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. J. Clin. Investig. 122, 2176–2194 (2012).
doi: 10.1172/JCI41636
Puri, P. et al. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology (Baltim., Md.) 46, 1081–1090 (2007).
doi: 10.1002/hep.21763
Araya, J. et al. Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin. Sci. (Lond., Engl.: 1979) 106, 635–643 (2004).
doi: 10.1042/CS20030326
Johnson, N. A. et al. Noninvasive assessment of hepatic lipid composition: advancing understanding and management of fatty liver disorders. Hepatology (Baltim., Md.) 47, 1513–1523 (2008).
doi: 10.1002/hep.22220
Hamilton, G. et al. In vivo characterization of the liver fat (1)H MR spectrum. NMR Biomed. 24, 784–790 (2011).
doi: 10.1002/nbm.1622
Lundbom, J. et al. Long-TE 1H MRS suggests that liver fat is more saturated than subcutaneous and visceral fat. NMR Biomed. 24, 238–245 (2011).
doi: 10.1002/nbm.1580
Gajdosik, M. et al. Ultrashort-TE stimulated echo acquisition mode (STEAM) improves the quantification of lipids and fatty acid chain unsaturation in the human liver at 7 T. NMR Biomed. 28, 1283–1293 (2015).
doi: 10.1002/nbm.3382
Donnelly, K. L. et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J. Clin. Investig. 115, 1343–1351 (2005).
doi: 10.1172/JCI23621
Bandsma, R. H. et al. Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to hyperlipidemia in glycogen storage disease type 1a. Pediatr. Res. 63, 702–707 (2008).
doi: 10.1203/PDR.0b013e31816c9013
Hudgins, L. C., Parker, T. S., Levine, D. M. & Hellerstein, M. K. A dual sugar challenge test for lipogenic sensitivity to dietary fructose. J. Clin. Endocrinol. Metab. 96, 861–868 (2011).
doi: 10.1210/jc.2010-2007
Peter, A. et al. Relationships between hepatic stearoyl-CoA desaturase-1 activity and mRNA expression with liver fat content in humans. Am. J. Physiol. Endocrinol. Metab. 300, E321–326 (2011).
doi: 10.1152/ajpendo.00306.2010
Timlin, M. T., Barrows, B. R. & Parks, E. J. Increased dietary substrate delivery alters hepatic fatty acid recycling in healthy men. Diabetes 54, 2694–2701 (2005).
doi: 10.2337/diabetes.54.9.2694
Hodson, L. Hepatic fatty acid synthesis and partitioning: the effect of metabolic and nutritional state. Proc. Nutr. Soc. 78, 126–134 (2019).
doi: 10.1017/S0029665118002653
Kim, C. W. et al. Acetyl CoA carboxylase inhibition reduces hepatic steatosis but elevates plasma triglycerides in mice and humans: a bedside to bench investigation. Cell Metab. 26, 394–406.e396 (2017).
doi: 10.1016/j.cmet.2017.07.009
Loomba, R. et al. GS-0976 reduces hepatic steatosis and fibrosis markers in patients with nonalcoholic fatty liver disease. Gastroenterology 155, 1463–1473.e1466 (2018).
doi: 10.1053/j.gastro.2018.07.027
Lawitz, E. J. et al. Acetyl-CoA carboxylase inhibitor GS-0976 for 12 weeks reduces hepatic de novo lipogenesis and steatosis in patients with nonalcoholic steatohepatitis. Clin. Gastroenterol. Hepatol. 16, 1983–1991.e1983 (2018).
doi: 10.1016/j.cgh.2018.04.042
Frahm, J. et al. Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn. Reson. Med. 9, 79–93 (1989).
doi: 10.1002/mrm.1910090110
Tkac, I., Starcuk, Z., Choi, I. Y. & Gruetter, R. In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time. Magn. Reson. Med. 41, 649–656 (1999).
doi: 10.1002/(SICI)1522-2594(199904)41:4<649::AID-MRM2>3.0.CO;2-G
Dong, Z., Dreher, W. & Leibfritz, D. Experimental method to eliminate frequency modulation sidebands in localized in vivo 1H MR spectra acquired without water suppression. Magn. Reson. Med. 51, 602–606 (2004).
doi: 10.1002/mrm.10716
Diraison, F., Pachiaudi, C. & Beylot, M. In vivo measurement of plasma cholesterol and fatty acid synthesis with deuterated water: determination of the average number of deuterium atoms incorporated. Metab.: Clin. Exp. 45, 817–821 (1996).
doi: 10.1016/S0026-0495(96)90152-3
Dempster, P. & Aitkens, S. A new air displacement method for the determination of human body composition. Med. Sci. Sports Exerc. 27, 1692–1697 (1995).
doi: 10.1249/00005768-199512000-00017
Siri, W. E. Body composition from fluid spaces and density: analysis of methods. 1961. Nutrition (Burbank, Los Angeles County, CA) 9, 480–491; discussion 480, 492 (1993).
Lofgren, L. et al. The BUME method: a novel automated chloroform-free 96-well total lipid extraction method for blood plasma. J. Lipid Res. 53, 1690–1700 (2012).
doi: 10.1194/jlr.D023036
Lofgren, L., Forsberg, G. B. & Stahlman, M. The BUME method: a new rapid and simple chloroform-free method for total lipid extraction of animal tissue. Sci. Rep. 6, 27688 (2016).
doi: 10.1038/srep27688
Murphy, R. C. et al. Detection of the abundance of diacylglycerol and triacylglycerol molecular species in cells using neutral loss mass spectrometry. Anal. Biochem. 366, 59–70 (2007).
doi: 10.1016/j.ab.2007.03.012
Steele, R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann. N. Y. Acad. Sci. 82, 420–430 (1959).
doi: 10.1111/j.1749-6632.1959.tb44923.x