title: Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX (JJL, JEL, YH, and JRT); the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX (MAR-R); Metabolic Solutions Inc., Nashua, NH (DAW); and the Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO (EJP).
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: From the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX (JJL, JEL, YH, and JRT); the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX (MAR-R); Metabolic Solutions Inc., Nashua, NH (DAW); and the Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO (EJP).
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Lambert
authors.affiliation: From the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX (JJL, JEL, YH, and JRT); the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX (MAR-R); Metabolic Solutions Inc., Nashua, NH (DAW); and the Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO (EJP).
authors.forename: Yelena
authors.initials: Y
authors.lastname: Hovhannisyan
authors.affiliation: From the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX (JJL, JEL, YH, and JRT); the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX (MAR-R); Metabolic Solutions Inc., Nashua, NH (DAW); and the Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO (EJP).
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ramos-Roman
authors.affiliation: From the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX (JJL, JEL, YH, and JRT); the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX (MAR-R); Metabolic Solutions Inc., Nashua, NH (DAW); and the Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO (EJP).
authors.forename: Justin R
authors.initials: JR
authors.lastname: Trombold
authors.affiliation: From the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX (JJL, JEL, YH, and JRT); the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX (MAR-R); Metabolic Solutions Inc., Nashua, NH (DAW); and the Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO (EJP).
authors.forename: David A
authors.initials: DA
authors.lastname: Wagner
authors.affiliation: From the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX (JJL, JEL, YH, and JRT); the Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX (MAR-R); Metabolic Solutions Inc., Nashua, NH (DAW); and the Department of Nutrition and Exercise Physiology, School of Medicine, University of Missouri, Columbia, MO (EJP).
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Parks
mesh_terms: D050154:Adiposity; D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D017666:Deuterium Oxide / Q000378:metabolism; D018752:Diet, Fat-Restricted; D005229:Fatty Acids, Monounsaturated / Q000097:blood* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050155:Lipogenesis; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism; D050177:Overweight / Q000503:physiopathology; D019308:Palmitic Acid / Q000097:blood / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; C008757:palmitoleic acid; D019308:Palmitic Acid; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D017666:Deuterium Oxide
keywords: VLDL triacylglycerol; biomarker; lipogenesis; palmitoleic fatty acid; stearoyl-CoA desaturase