CoChat
Sign Up
Cited by 101Liver Disease Diagnosis and TreatmentFatty Acid Research and HealthDiet, Metabolism, and Disease

Different Serum Free Fatty Acid Profiles in NAFLD Subjects and Healthy Controls after Oral Fat Load

Open access
Gambino, Roberto, Bugianesi, Elisabetta, Rosso, Chiara, Mezzabotta, Lavinia, Pinach, Silvia, Alemanno, Natalina, Saba, Francesca, Cassader, Maurizio·2016·International Journal of Molecular Sciences
DOI 10.3390/ijms17040479PMC PMC4848935
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Free fatty acid (FFA) metabolism can impact on metabolic conditions, such as obesity and nonalcoholic fatty liver disease (NAFLD). This work studied the increase in total FFA shown in NAFLD subjects to possibly characterize which fatty acids significantly accounted for the whole increase. Methods: 21 patients with NAFLD were selected according to specified criteria. The control group consisted of nine healthy subjects. All subjects underwent an oral standard fat load. Triglycerides; cholesterol; FFA; glucose and insulin were measured every 2 h with the determination of fatty acid composition of FFA. Results: higher serum FFA levels in NAFLD subjects are mainly due to levels of oleic, palmitic and linoleic acids at different times. Significant increases were shown for docosahexaenoic acid, linolenic acid, eicosatrienoic acid, and arachidonic acid, although this was just on one occasion. In the postprandial phase, homeostatic model assessment HOMA index positively correlated with the ω3/ω6 ratio in NAFLD patients. Conclusions: the higher serum levels of FFA in NAFLD subjects are mainly due to levels of oleic and palmitic acids which are the most abundant circulating free fatty acids. This is almost exactly corresponded with significant increases in linoleic acid. An imbalance in the n-3/n-6 fatty acids ratio could modulate postprandial responses with more pronounced effects in insulin-resistant subjects, such as NAFLD patients.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/ijms17040479

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 38

  1. [1]Kooner J.S. Baliga R.R. Wilding J. Crook D. Packard C.J. Banks L.M. Peart S. Aitman T.J. Scott J. Abdominal obesity, impaired nonesterified fatty acid suppression, and insulin-mediated glucose disposal are early metabolic abnormalities in families with premature myocardial infarction Arterioscler. Thromb. Vasc. Biol. 1998 18 1021 1026 10.1161/01.ATV.18.7.1021 9672061 · DOI
  2. [2]Zoratti R. Godsland I.F. Chaturvedi N. Crook D. Crook D. Stevenson J.C. McKeigue P.M. Relation of plasma lipids to insulin resistance, nonesterified fatty acid levels, and body fat in men from three ethnic groups: Relevance to variation in risk of diabetes and coronary disease Metabolism 2000 49 245 252 10.1016/S0026-0495(00)91507-5 10690953 · DOI
  3. [3]Musso G. Gambino R. Cassader M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD) Prog. Lipid Res. 2009 48 1 26 10.1016/j.plipres.2008.08.001 18824034 · DOI
  4. [4]Musso G. Gambino R. de Michieli F. Biroli G. Fagà E. Pagano G. Cassader M. Association of liver disease with postprandial large intestinal triglyceride-rich lipoprotein accumulation and pro/antioxidant imbalance in normolipidemic non-alcoholic steatohepatitis Ann. Med. 2008 40 383 394 10.1080/07853890801946515 18484349 · DOI
  5. [5]De Almeida I.T. Cortez-Pinto H. Fidalgo G. Rodrigues D. Camilo M.E. Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis Clin. Nutr. 2002 21 219 223 10.1054/clnu.2001.0529 12127930 · DOI · Paper page
  6. [6]Seidelin K.N. Myrup B. Fischer-Hansen B. n-3 fatty acids in adipose tissue and coronary artery disease are inversely related Am. J. Clin. Nutr. 1992 55 1117 1119 1595583
  7. [7]Musso G. Gambino R. Pacini G. de Michieli F. Cassader M. Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: Dysregulated enteroadipocyte axis as a novel feature of fatty liver Am. J. Clin. Nutr. 2009 89 558 567 10.3945/ajcn.2008.26720 19141695 · DOI · Paper page
  8. [8]Marinou K. Adiels M. Hodson L. Frayn K.N. Karpe F. Fielding B.A. Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men Br. J. Nutr. 2011 105 857 865 10.1017/S0007114510004472 21251339 · DOI · Paper page
  9. [9]Nelson R.H. Basu R. Johnson C.M. Rizza R.A. Miles J.M. Splanchnic spillover of extracellular lipase-generated fatty acids in overweight and obese humans Diabetes 2007 56 2878 2884 10.2337/db07-0812 17881612 · DOI
  10. [10]Hardy S. El-Assaad W. Przybytkowski E. Joly E. Prentki M. Langelier Y. Saturated fatty acid induced-apoptosis in MDA-MB-231 breast cancer cells—A role for cardiolipin J. Biol. Chem. 2003 278 31861 31870 10.1074/jbc.M300190200 12805375 · DOI
  11. [11]Musso G. Gambino R. Durazzo M. Biroli G. Carello M. Faga E. Pacini G. de Michieli F. Rabbione L. Premoli A. Adipokines in NASH: Postprandial lipid metabolism as a link between adiponectin and liver disease Hepatology 2005 42 1175 1183 10.1002/hep.20896 16231364 · DOI
  12. [12]Okere I. Chandler M. McElfresh T. Rennison J.H. Sharov V. Sabbah H.N. Tserng K.T. Hoit B.D. Ernsberger P. Young M.E. Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin Am. J. Physiol. Heart Circ. Physiol. 2006 291 H38 H44 10.1152/ajpheart.01295.2005 16443671 · DOI · Paper page
  13. [13]Wang D. Wei Y.R. Pagliassotti M.J. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis Endocrinology 2006 147 943 951 10.1210/en.2005-0570 16269465 · DOI
  14. [14]Spector A.A. Yorek M.A. Membrane lipid-composition and cellular function J. Lipid Res. 1985 26 1015 1035 3906008
  15. [15]Borradaile N.M. Han X. Harp J.D. Gale S.E. Ory D.S. Schaffer J.E. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death J. Lipid Res. 2006 47 2726 2737 10.1194/jlr.M600299-JLR200 16960261 · DOI
  16. [18]Nakamura S. Takamura T. Matsuzawa-Nagata N. Takayama H. Misu H. Noda H. Nabemoto S. Kurita S. Ota T. Ando H. Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria J. Biol. Chem. 2009 284 14809 14818 10.1074/jbc.M901488200 19332540 PMC2685662 · DOI · Paper page
  17. [20]Summers S.A. Ceramides in insulin resistance and lipotoxicity Prog. Lipid Res. 2006 45 42 72 10.1016/j.plipres.2005.11.002 16445986 · DOI
  18. [21]Maeda K. Cao H. Kono K. Gorgun C.Z. Furuhashi M. Uysal K.T. Cao Q. Atsumi G. Malone H. Krishnan B. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes Cell Metab. 2005 1 107 119 10.1016/j.cmet.2004.12.008 16054052 · DOI
  19. [22]Yli-Jama P. Meyer H.E. Ringstad J. Pedersen J.I. Serum free fatty acid pattern and risk of myocardial infarction: A case-control study J. Intern. Med. 2002 251 19 28 10.1046/j.1365-2796.2002.00922.x 11851861 · DOI
  20. [23]Miles J.M. Park Y.S. Walewicz D. Russell-Lopez C. Windsor S. Isley W.L. Coppack S.W. Harris W.S. Systemic and forearm triglyceride metabolism: Fate of lipoprotein lipase-generated glycerol and free fatty acids Diabetes 2004 53 521 527 10.2337/diabetes.53.3.521 14988233 · DOI
  21. [24]Havel R.J. Hamilton R.L. Hepatic catabolism of remnant lipoproteins: Where the action is Arterioscler. Thromb. Vasc. Biol. 2004 24 213 215 14766735
  22. [25]Griffiths A.J. Humphreys S.M. Clark M.L. Fielding B.A. Frayn K.N. Immediate metabolic availability of dietary fat in combination with carbohydrate Am. J. Clin. Nutr. 1994 59 53 59 8279403
  23. [26]Weiss E.P. Fields D.A. Mittendorfer B. Dorien Haverkort A.M. Klein S. Reproducibility of postprandial lipemia test and validity of an abbreviated 4-h test Metabolism 2008 57 1479 1485 10.1016/j.metabol.2008.05.020 18803956 PMC2585379 · DOI
  24. [27]Musso G. Gambino R. De Michieli F. Cassader M. Rizzetto M. Durazzo M. Fagà E. Silli B. Pagano G. Dietary habits and their relation to insulin resistance in nonalcoholic steatohepatitis Hepatology 2003 37 909 916 10.1053/jhep.2003.50132 12668986 · DOI
  25. [28]Cassader M. Gambino R. Musso G. Depetris N. Mecca F. Cavallo-Perin P. Pacini G. Rizzetto M. Pagano G. Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients Lipids 2001 36 1117 1124 10.1007/s11745-001-0822-5 11768156 · DOI
  26. [29]Ntambi J.M. Miyazaki M. Regulation of stearoyl-CoA desaturases and role in metabolism Prog. Lipid Res. 2004 43 91 104 10.1016/S0163-7827(03)00039-0 14654089 · DOI
  27. [30]Inagaki K. Aki T. Fukuda Y. Kawamoto S. Shigeta S. Ono K. Suzuki O. Identification and expression of a rat fatty acid elongase involved in the biosynthesis of C18 fatty acids Biosci. Biotechnol. Biochem. 2002 66 613 621 10.1271/bbb.66.613 12005057 · DOI
  28. [31]Sampath H. Ntambi J.M. The fate and intermediary metabolism of stearic acid Lipids 2005 40 1187 1191 10.1007/s11745-005-1484-z 16477801 · DOI
  29. [32]Sun Y. Hao M.M. Luo Y. Liang C.P. Silver D.L. Cheng C. Maxfield F.R. Tall A.R. Stearoyl-CoA desaturase inhibits ATP-binding cassette transporter A1-mediated cholesterol efflux and modulates membrane domain structure J. Biol. Chem. 2003 278 5813 5820 10.1074/jbc.M208687200 12482877 · DOI
  30. [33]Attie A.D. Krauss R.M. Gray-Keller M.P. Brownlie A. Miyazaki M. Kastelein J.J. Lusis A.J. Stalenhoef A.F. Stoehr J.P. Hayden M.R. Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia J. Lipid Res. 2002 43 1899 1907 10.1194/jlr.M200189-JLR200 12401889 · DOI
  31. [34]Le H.D. Meisel J.A. de Meijer V.E. Gura K.M. Puder M. The essentiality of arachidonic acid and docosahexaenoic acid Prostaglandins Leukot. Essent. Fatty Acids 2009 81 165 170 10.1016/j.plefa.2009.05.020 19540099 PMC3361712 · DOI
  32. [35]Brenna J.T. Salem N. Jr. Sinclair A.J. Cunnane S.C. α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans Prostaglandins Leukot. Essent. Fatty Acids 2009 80 85 91 10.1016/j.plefa.2009.01.004 19269799 · DOI
  33. [36]Roche H.M. Gibney M.J. Effect of long-chain n-3 polyunsaturated fatty acids on fasting and postprandial triacylglycerol metabolism Am. J. Clin. Nutr. 2000 71 232s 237s 10617977
  34. [37]Tulk H. Robinson L. Modifying the n-6/n-3 polyunsaturated fatty acid ratio of a high-saturated fat challenge does not acutely attenuate postprandial changes in inflammatory markers in men with metabolic syndrome Metabolism 2009 58 1709 1716 10.1016/j.metabol.2009.05.031 19625064 · DOI
  35. [38]Song Z. Yang L. Shu G. Lu H. Sun G. Effects of the n-6/n-3 polyunsaturated fatty acids ratio on postprandial metabolism in hypertriacylglycerolemia patients Lipids Health Dis. 2013 12 181 188 10.1186/1476-511X-12-181 24325472 PMC4029461 · DOI
  36. [39]Warnick G.R. Albers J.J. A comprehensive evolution of the heparin manganese precipitation procedure for estimating high density lipoprotein cholesterol J. Lipid Res. 1978 29 65 76 202660
  37. [40]Gidez L.I. Miller G.J. Burnstein M. Slagle S. Eder H.A. Separation and quantitation of subclasses of human plasma HDL by a single precipitation procedure J. Lipid Res. 1982 23 1206 1216 7175378
  38. [43]Matsuzawa T. Mishima K. Nishii M. Ito M. Serum fatty acids analysis by high performance liquid chromatography, after enzymatic hydrolysis and isolation by Sep-Pak C18 minicolumn Biochem. Int. 1987 15 693 702 3435535

Cited by

Sorted by citations

Authors
Gambino, R., Bugianesi, E., Rosso, C., Mezzabotta, L., Pinach, S., Alemanno, N., Saba, F., & Cassader, M.
Affiliations
University of Turin (IT)
Corresponding author
Gambino, Roberto
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2016-03-31
Volume
17
Issue
4
Pages
479
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms17040479
PMC
PMC4848935
OpenAlex
W2316493884
Cited by
101
References
5
Citations by year
2026: 5 · 2025: 7 · 2024: 14 · 2023: 11 · 2022: 6 · 2021: 12 · 2020: 13 · 2019: 12 · 2018: 7 · 2017: 12 · 2016: 2
FWCI
10.32
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Funded by FP7/2007-2013 under grant agreement n°HEALTH-F2-2009-241762 for the project FLIP and by PRIN 2009ARYX4T.
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
non-alcoholic fatty liver disease, free fatty acids, oral fat load, postprandial lipemia, fatty acid composition, oleic acid, palmitic acid, linoleic acid, n-6/n-3 ratio, HOMA index, insulin resistance, docosahexaenoic acid, arachidonic acid
MeSH terms
Adult, Blood Glucose, Cholesterol, Chromatography, High Pressure Liquid, Colorimetry, Fatty Acids, Nonesterified, Female, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Triglycerides, Fatty Acids, Omega-3, Case-Control Studies, Fatty Acids, Omega-6, Diet, High-Fat, Non-alcoholic Fatty Liver Disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review