Associations of Erythrocyte Fatty Acids in the De Novo Lipogenesis Pathway with Proxies of Liver Fat Accumulation in the EPIC-Potsdam Study

Jacobs, Simone; Jäger, Susanne; Jansen, Eugène; Stefan, Norbert; Boeing, Heiner; Kröger, Janine

doi:10.1371/journal.pone.0127368

Cited by 27 publications

(32 citation statements)

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“…Several studies [ 12 , 36 , 37 ] examined the associations of SFAs with liver function markers, with mixed findings. Even-chain SFAs were positively associated with hepatic markers in one study [ 12 ], but not associated in several other studies [ 36 , 37 ], with no evidence that odd-chain or very-long-chain SFAs were associated with these markers. In our study, odd-chain SFAs were inversely associated, C18:0 was positively associated with the three hepatic markers included, and very-long-chain SFAs were inversely associated with GGT.…”

Section: Discussionmentioning

confidence: 99%

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study

Zheng

Sharp

Imamura

et al. 2017

BMC Med

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BackgroundAccumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways.MethodsWe measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested.ResultsHigher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption.ConclusionsSubtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0968-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study

Zheng

Sharp

Imamura

et al. 2017

BMC Med

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“…Different fatty acid metabolic parameters were calculated. The ratio of the concentration of PA/LA and PA/ARA were taken as an indirect measurement of de novo lipogenesis (Jacobs et al, 2015 ). Omega-6 index, taken as an index of the impact of dietary intake of omega-6 on erythrocyte concentrations of omega-6 highly polyunsaturated fatty acids (HPUFAs), was calculated as the ratio between the sum of the concentrations of omega-6 HPUFAs (those with 20 or more carbon atoms and three or more double bonds) and the sum of total fatty acids: (20:4n-6+20:3n-6+22:4n-6+22:5n-6)/(sum of total fatty acids), similarly to how the omega-3 index is calculated (Harris and Von Schacky, 2004 ).…”

Section: Methodsmentioning

confidence: 99%

Polymorphism rs1761667 in the CD36 Gene Is Associated to Changes in Fatty Acid Metabolism and Circulating Endocannabinoid Levels Distinctively in Normal Weight and Obese Subjects

et al. 2017

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The multifunctional CD36 scavenger receptor facilitates fatty acid (FA) uptake and oxidation and it has been involved in the pathophysiology related to dysfunctional FA metabolism. The common variant in the CD36 gene, rs1761667 (A/G), whose allele A is characterized by a reduced protein expression, has been associated with taste sensitivity to and preference for fat. We therefore aimed at evaluating whether the CD36 polymorphism may influence fatty acid metabolism and endocannabinoid biosynthesis in normal weight (NW) and obese (OB) subjects. Red blood cell (RBC) fatty acid composition, and plasma endocannabinoid levels were determined. In NW subjects with AA genotype was found a marked reduction of RBC saturated fatty acids and palmitic/linoleic ratio (PA/LA), considered as de novo lipogenesis (DNL) biomarkers. Remarkably, to the reduction of DNL biomarkers corresponded an increase of omega-6 index, an indirect marker of the impact on fatty acid metabolism of dietary omega-6 fatty acids, endocannabinoid levels and a higher waist/hip ratio. The presence of the G allele was instead associated with increased endocannabinoid plasma levels and a trend for increased waist/hip ratio in obese subjects, even though exhibited decreased BMI with respect to those with AA genotype. These data indicate that the CD36 polymorphism, rs1761667, leads to a distinct metabolic pattern in NW and in OB subjects. Therefore, their determination may be crucial in developing personalized therapeutic strategies for ameliorating dyslipidemia and other metabolic disorders.

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“…Indeed, the lipogenic index was higher after high carbohydrate feeding compared to a high fat diet. This index has been also analyzed in erythrocyte membranes in the EPIC-Potsdam Study and found to positively correlate with proxies of liver fat content [ 67 ]. Other DNL indices include the desaturation index, measuring the ratio of oleic acid (18:1n9) to stearic acid (18:0).…”

Section: Fatty Acid Profilingmentioning

confidence: 99%

Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease

Paglialunga

Dehn

2016

Lipids Health Dis

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Non-alcoholic fatty liver disease (NAFLD) is heralded as the next big global epidemic. Hepatic de novo lipogenesis (DNL), the synthesis of new fatty acids from non-lipid sources, is thought to play a pivotal role in the development of NAFLD. While there is currently no NAFLD-specific therapeutic agent available, pharmaceutical drugs aimed at reducing hepatic fat accretion may prove to be a powerful ally in the treatment and management of this disease. With a focus on NAFLD, the present review summarizes current techniques examining DNL from a clinical perspective, and describes the merits and limitations of three commonly used assays; stable-label isotope tracer studies, fatty acid indexes and indirect calorimetry as non-invasive measures of hepatic DNL. Finally, the application of DNL assessments in the pharmacological and nutraceutical treatment of NAFLD/NASH is summarized. In a clinical research setting, measures of DNL are an important marker in the development of anti-NAFLD treatments.

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Associations of Erythrocyte Fatty Acids in the De Novo Lipogenesis Pathway with Proxies of Liver Fat Accumulation in the EPIC-Potsdam Study

Cited by 27 publications

References 54 publications

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study

Polymorphism rs1761667 in the CD36 Gene Is Associated to Changes in Fatty Acid Metabolism and Circulating Endocannabinoid Levels Distinctively in Normal Weight and Obese Subjects

Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease

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