Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease

Jukka Westerbacka, Anna Kotronen (Corresponding Author), Barbara A. Fielding, John Wahren, Leanne Hodson, Julia Perttilä, Tuulikki Seppänen-Laakso, Tapani Suortti, Johanna Arola, Rolf Hultcrantz, Sandra Castillo, Vesa M. Olkkonen, Keith N. Frayn, Matej Orešič, Hannele Yki-Järvinen

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Background & Aims

Animal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD.

Methods

We performed hepatic venous catheterization studies in combination with [2H2]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatography coupled to mass spectrometry.

Results

Concentrations of the endocannabinoid 2-arachidonoylglycerol were higher in arterialized (91 ± 33 μg/L basally) than in hepatic venous (51 ± 19 μg/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglycerides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states.

Conclusions

The human fatty liver takes up 2-arachidonoylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.

Original languageEnglish
Pages (from-to)1961-1971
Number of pages11
JournalGastroenterology
Volume139
Issue number6
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Fingerprint

Endocannabinoids
Viscera
Nonesterified Fatty Acids
Lipids
Liver
Triglycerides
Hepatic Veins
Fatty Liver
Fasting
Insulin
Biopsy
Stearates
Ketone Bodies
Lipogenesis
Palmitates
Linoleic Acid
Oleic Acid
Non-alcoholic Fatty Liver Disease
Catheterization
Liquid Chromatography

Keywords

  • hepatic steatosis
  • hepatic vein
  • endocannabinoids
  • lipolysis

Cite this

Westerbacka, J., Kotronen, A., Fielding, B. A., Wahren, J., Hodson, L., Perttilä, J., ... Yki-Järvinen, H. (2010). Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease. Gastroenterology, 139(6), 1961-1971. https://doi.org/10.1053/j.gastro.2010.06.064
Westerbacka, Jukka ; Kotronen, Anna ; Fielding, Barbara A. ; Wahren, John ; Hodson, Leanne ; Perttilä, Julia ; Seppänen-Laakso, Tuulikki ; Suortti, Tapani ; Arola, Johanna ; Hultcrantz, Rolf ; Castillo, Sandra ; Olkkonen, Vesa M. ; Frayn, Keith N. ; Orešič, Matej ; Yki-Järvinen, Hannele. / Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease. In: Gastroenterology. 2010 ; Vol. 139, No. 6. pp. 1961-1971.
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title = "Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease",
abstract = "Background & AimsAnimal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD.MethodsWe performed hepatic venous catheterization studies in combination with [2H2]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatography coupled to mass spectrometry.ResultsConcentrations of the endocannabinoid 2-arachidonoylglycerol were higher in arterialized (91 ± 33 μg/L basally) than in hepatic venous (51 ± 19 μg/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglycerides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states.ConclusionsThe human fatty liver takes up 2-arachidonoylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.",
keywords = "hepatic steatosis, hepatic vein, endocannabinoids, lipolysis",
author = "Jukka Westerbacka and Anna Kotronen and Fielding, {Barbara A.} and John Wahren and Leanne Hodson and Julia Perttil{\"a} and Tuulikki Sepp{\"a}nen-Laakso and Tapani Suortti and Johanna Arola and Rolf Hultcrantz and Sandra Castillo and Olkkonen, {Vesa M.} and Frayn, {Keith N.} and Matej Orešič and Hannele Yki-J{\"a}rvinen",
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Westerbacka, J, Kotronen, A, Fielding, BA, Wahren, J, Hodson, L, Perttilä, J, Seppänen-Laakso, T, Suortti, T, Arola, J, Hultcrantz, R, Castillo, S, Olkkonen, VM, Frayn, KN, Orešič, M & Yki-Järvinen, H 2010, 'Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease', Gastroenterology, vol. 139, no. 6, pp. 1961-1971. https://doi.org/10.1053/j.gastro.2010.06.064

Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease. / Westerbacka, Jukka; Kotronen, Anna (Corresponding Author); Fielding, Barbara A.; Wahren, John; Hodson, Leanne; Perttilä, Julia; Seppänen-Laakso, Tuulikki; Suortti, Tapani; Arola, Johanna; Hultcrantz, Rolf; Castillo, Sandra; Olkkonen, Vesa M.; Frayn, Keith N.; Orešič, Matej; Yki-Järvinen, Hannele.

In: Gastroenterology, Vol. 139, No. 6, 2010, p. 1961-1971.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease

AU - Westerbacka, Jukka

AU - Kotronen, Anna

AU - Fielding, Barbara A.

AU - Wahren, John

AU - Hodson, Leanne

AU - Perttilä, Julia

AU - Seppänen-Laakso, Tuulikki

AU - Suortti, Tapani

AU - Arola, Johanna

AU - Hultcrantz, Rolf

AU - Castillo, Sandra

AU - Olkkonen, Vesa M.

AU - Frayn, Keith N.

AU - Orešič, Matej

AU - Yki-Järvinen, Hannele

PY - 2010

Y1 - 2010

N2 - Background & AimsAnimal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD.MethodsWe performed hepatic venous catheterization studies in combination with [2H2]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatography coupled to mass spectrometry.ResultsConcentrations of the endocannabinoid 2-arachidonoylglycerol were higher in arterialized (91 ± 33 μg/L basally) than in hepatic venous (51 ± 19 μg/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglycerides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states.ConclusionsThe human fatty liver takes up 2-arachidonoylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.

AB - Background & AimsAnimal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD.MethodsWe performed hepatic venous catheterization studies in combination with [2H2]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatography coupled to mass spectrometry.ResultsConcentrations of the endocannabinoid 2-arachidonoylglycerol were higher in arterialized (91 ± 33 μg/L basally) than in hepatic venous (51 ± 19 μg/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglycerides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states.ConclusionsThe human fatty liver takes up 2-arachidonoylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.

KW - hepatic steatosis

KW - hepatic vein

KW - endocannabinoids

KW - lipolysis

U2 - 10.1053/j.gastro.2010.06.064

DO - 10.1053/j.gastro.2010.06.064

M3 - Article

VL - 139

SP - 1961

EP - 1971

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 6

ER -