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Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland.
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland: Minerva Medical Research Institute, Helsinki, Finland; cDiabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
Department of Surgical Sciences, Division of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
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2010 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 139, no 6, p. 1961-1971.e1Article in journal (Refereed) Published
Abstract [en]

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 [(2)H(2)]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.

Place, publisher, year, edition, pages
Saunders Elsevier, 2010. Vol. 139, no 6, p. 1961-1971.e1
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-63633DOI: 10.1053/j.gastro.2010.06.064ISI: 000284843600035PubMedID: 20600015Scopus ID: 2-s2.0-78649695476OAI: oai:DiVA.org:oru-63633DiVA, id: diva2:1169199
Note

Funding agencies:

Academy of Finland

Sigrid Juselius Foundation

Finnish Diabetes Research Foundation

Orion Foundation

Jalmari and Rauha Ahokas Foundation

Biomedicum Helsinki Foundation

Novo Nordisk Foundation

European Commission LSHM-CT-2005-018734

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-18Bibliographically approved

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Oresic, Matej

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