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

Joseph J. Lee, Jennifer E. Lambert, Yelena Hovhannisyan, Maria A. Ramos-Roman, Justin R. Trombold, David A. Wagner, Elizabeth J. Parks

Research output: Contribution to journalArticle

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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 [SCD1(16)] in plasma triacylglycerol FA has been used as an index to reflect liver SCD1(16) 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 (DNLMeas). 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 DNLMeas (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1(16) 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% oxf 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 DNLMeas (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDLtriacylglycerols corresponded to a stronger signal of elevated DNL. Conclusion: The current data provide support for the use of the VLDLtriacylglycerol 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. This trial was registered at clinicaltrials.gov as NCT01371396.

Original languageEnglish (US)
Pages (from-to)34-43
Number of pages10
JournalAmerican Journal of Clinical Nutrition
Volume101
Issue number1
DOIs
StatePublished - Jan 1 2015

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Lipogenesis
Fatty Liver
Stearoyl-CoA Desaturase
Liver Diseases
VLDL Lipoproteins
Triglycerides
Fatty Acids
Fats
Liver
Nonesterified Fatty Acids
Isotopes
Gas Chromatography-Mass Spectrometry
Biomarkers
Deuterium
Gas Chromatography
Insulin Resistance
palmitoleic acid
Mass Spectrometry
Magnetic Resonance Spectroscopy
Diet

Keywords

  • Biomarker
  • Lipogenesis
  • Palmitoleic fatty acid
  • Stearoyl-CoA desaturase
  • VLDL triacylglycerol

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis. / Lee, Joseph J.; Lambert, Jennifer E.; Hovhannisyan, Yelena; Ramos-Roman, Maria A.; Trombold, Justin R.; Wagner, David A.; Parks, Elizabeth J.

In: American Journal of Clinical Nutrition, Vol. 101, No. 1, 01.01.2015, p. 34-43.

Research output: Contribution to journalArticle

Lee, Joseph J. ; Lambert, Jennifer E. ; Hovhannisyan, Yelena ; Ramos-Roman, Maria A. ; Trombold, Justin R. ; Wagner, David A. ; Parks, Elizabeth J. / Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis. In: American Journal of Clinical Nutrition. 2015 ; Vol. 101, No. 1. pp. 34-43.
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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 [SCD1(16)] in plasma triacylglycerol FA has been used as an index to reflect liver SCD1(16) 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 (DNLMeas). 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 DNLMeas (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1(16) 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{\%} oxf 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 DNLMeas (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDLtriacylglycerols corresponded to a stronger signal of elevated DNL. Conclusion: The current data provide support for the use of the VLDLtriacylglycerol 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. This trial was registered at clinicaltrials.gov as NCT01371396.",
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T1 - Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis

AU - Lee, Joseph J.

AU - Lambert, Jennifer E.

AU - Hovhannisyan, Yelena

AU - Ramos-Roman, Maria A.

AU - Trombold, Justin R.

AU - Wagner, David A.

AU - Parks, Elizabeth J.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 [SCD1(16)] in plasma triacylglycerol FA has been used as an index to reflect liver SCD1(16) 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 (DNLMeas). 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 DNLMeas (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1(16) 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% oxf 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 DNLMeas (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDLtriacylglycerols corresponded to a stronger signal of elevated DNL. Conclusion: The current data provide support for the use of the VLDLtriacylglycerol 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. This trial was registered at clinicaltrials.gov as NCT01371396.

AB - 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 [SCD1(16)] in plasma triacylglycerol FA has been used as an index to reflect liver SCD1(16) 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 (DNLMeas). 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 DNLMeas (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1(16) 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% oxf 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 DNLMeas (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDLtriacylglycerols corresponded to a stronger signal of elevated DNL. Conclusion: The current data provide support for the use of the VLDLtriacylglycerol 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. This trial was registered at clinicaltrials.gov as NCT01371396.

KW - Biomarker

KW - Lipogenesis

KW - Palmitoleic fatty acid

KW - Stearoyl-CoA desaturase

KW - VLDL triacylglycerol

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