Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis

Am J Clin Nutr. 2015 Jan;101(1):34-43. doi: 10.3945/ajcn.114.092262. Epub 2014 Nov 19.

Abstract

Background: Biochemical evidence has linked the coordinate control of fatty acid (FA) synthesis with the activity of stearoyl-CoA desaturase-1 (SCD1). The ratio of 16:1n-7 to 16:0 [SCD1₁₆] in plasma triacylglycerol FA has been used as an index to reflect liver SCD1₁₆ activity and has been proposed as a biomarker of FA synthesis, although this use has not been validated by comparison with isotopically measured de novo lipogenesis (DNL(Meas)).

Objective: We investigated plasma lipid 16:1n-7 and FA indexes of elongation and desaturation in relation to lipogenesis.

Design: In this cross-sectional investigation of metabolism, 24 overweight adults, who were likely to have elevated DNL, consumed D2O for 10 d and had liver fat (LF) measured by magnetic resonance spectroscopy. Very-low-density lipoprotein (VLDL)-triacylglycerols and plasma free FA [nonesterified fatty acids (NEFAs)] were analyzed by using gas chromatography for the FA composition (molar percentage) and gas chromatography-mass spectrometry and gas chromatography-combustion isotope ratio mass spectrometry for deuterium enrichment.

Results: In all subjects, VLDL-triacylglycerol 16:1n-7 was significantly (P < 0.01) related to DNL(Meas) (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1₁₆ index, and the pattern in NEFAs echoed that of VLDL-triacylglycerols. Compared with subjects with low LF (3.1 ± 2.7%; n = 11), subjects with high LF (18.4 ± 3.6%; n = 13) exhibited a 45% higher VLDL-triacylglycerol 16:1n-7 molar percentage (P < 0.01), 16% of subjects had lower 18:2n-6 (P = 0.01), and 27% of subjects had higher DNL as assessed by using a published DNL index (ratio of 16:0 to 18:2n-6; P = 0.03), which was isotopically confirmed by DNL(Meas) (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDL-triacylglycerols corresponded to a stronger signal of elevated DNL.

Conclusion: The current data provide support for the use of the VLDL-triacylglycerol 16:1n-7 molar percentage as a biomarker for elevated liver fat when isotope use is not feasible; however, larger-scale confirmatory studies are needed.

Trial registration: ClinicalTrials.gov NCT01371396.

Keywords: VLDL triacylglycerol; biomarker; lipogenesis; palmitoleic fatty acid; stearoyl-CoA desaturase.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity
  • Adult
  • Algorithms
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Body Mass Index
  • Cross-Sectional Studies
  • Deuterium Oxide / metabolism
  • Diet, Fat-Restricted
  • Fatty Acids, Monounsaturated / blood*
  • Fatty Acids, Monounsaturated / metabolism
  • Fatty Acids, Nonesterified / blood
  • Female
  • Humans
  • Insulin Resistance
  • Lipogenesis*
  • Lipoproteins, VLDL / blood*
  • Lipoproteins, VLDL / metabolism
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / diet therapy
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Overweight / physiopathology
  • Palmitic Acid / blood
  • Palmitic Acid / metabolism
  • Stearoyl-CoA Desaturase / metabolism
  • Triglycerides / blood*
  • Triglycerides / metabolism
  • Up-Regulation*

Substances

  • Biomarkers
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Nonesterified
  • Lipoproteins, VLDL
  • Triglycerides
  • very low density lipoprotein triglyceride
  • palmitoleic acid
  • Palmitic Acid
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase
  • Deuterium Oxide

Associated data

  • ClinicalTrials.gov/NCT01371396