| 1. |
- Rosqvist, Fredrik, 1985-, et al.
(author)
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Fasting hepatic de novo lipogenesis is not reliably assessed using circulating fatty acid markers
- 2019
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In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 109:2, s. 260-268
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Journal article (peer-reviewed)abstract
- Background: Observational studies often infer hepatic de novo lipogenesis (DNL) by measuring circulating fatty acid (FA) markers; however, it remains to be elucidated whether these markers accurately reflect hepatic DNL. Objectives: We investigated associations between fasting hepatic DNL and proposed FA markers of DNL in subjects consuming their habitual diet. Methods: Fasting hepatic DNL was assessed using (H2O)-H-2(deuterated water) in 149 nondiabetic men and women and measuring the synthesis of very low-density lipoprotein triglyceride (VLDL-TG) palmitate. FA markers of blood lipid fractions were determined by gas chromatography. Results: Neither the lipogenic index (16: 0/18: 2n-6) nor the SCD index (16: 1n-7/16: 0) in VLDL-TG was associated with isotopically assessed DNL (r = 0.13, P = 0.1 and r = -0.08, P = 0.35, respectively). The relative abundances (mol%) of 14: 0, 16: 0, and 18: 0 in VLDL-TG were weakly (r <= 0.35) associated with DNL, whereas the abundances of 16: 1n-7, 18: 1n-7, and 18: 1n-9 were not associated. When the cohort was split by median DNL, only the abundances of 14: 0 and 18: 0 in VLDL-TG could discriminate between subjects having high (11.5%) and low(3.8%) fasting hepatic DNL. Based on a subgroup, FA markers in total plasma TG, plasma cholesteryl esters, plasma phospholipids, and red blood cell phospholipids were generally not associated with DNL. Conclusions: The usefulness of circulating FAs as markers of hepatic DNL in healthy individuals consuming their habitual diet is limited due to their inability to discriminate clearly between individuals with low and high fasting hepatic DNL.
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| 2. |
- Ruge, Toralph, et al.
(author)
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Fasted to fed trafficking of fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage.
- 2009
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X.
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Journal article (peer-reviewed)abstract
- Context: Absence or excess of adipose tissue are both associated with metabolic complications implying the importance of well-functioning adipose tissue present in normal amounts. Adipose tissue sequesters dietary fat and thus protects other tissues from excess fat exposure, especially following meals. Objective: Use of an integrative physiological technique to quantify trafficking of fatty acids (FA) in adipose tissue over a 24-h period. Methods: Adipose tissue FA handling was studied in response to three meals in eight healthy men by the combination of arterio-venous blood sampling, tissue blood flow, and specific labelling of FA tracing of exogenous and endogenous fat by stable isotope methodology. Results: The efficiency of adipose tissue FA uptake increased robustly with each meal. Chylomicron-triglyceride (TG) was the dominating source of FA. Adipose tissue fractional extraction of chylomicron-TG increased from 21+/-4 to 47+/-8% (p=0.03) between the first and last meal. Although adipose tissue lipoprotein lipase (LPL) action increased with time (2-fold), there was an even greater increase in FA re-esterification (3-fold), which led to a reduced spillover of chylomicron-derived FA, from 77+/-15 to 34+/-7% (p=0.04) comparing the end of the first and the third meal period. Increased uptake of VLDL-derived FA was observed, but spillover of VLDL-derived FA was only seen in the fasting state. Conclusion: Human adipose tissue has a significant potential to up-regulate fat storage during a normal day that goes beyond increased LPL activation. The adaptation towards increasing fat storage may provide an explanation for the beneficial properties of normal amounts of adipose tissue.
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| 3. |
- Adiels, Martin, 1976, et al.
(author)
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Optimization of N-methyl-N-[tert-butyldimethylsilyl]trifluoroacetamide as a derivatization agent for determining isotopic enrichment of glycerol in very-low density lipoproteins.
- 2010
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In: Rapid communications in mass spectrometry : RCM. - : Wiley. - 1097-0231 .- 0951-4198. ; 24:5, s. 586-592
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Journal article (peer-reviewed)abstract
- Stable isotope kinetic studies play an important role in the study of very-low density lipoprotein (VLDL) metabolism, including basic and clinical research. Today, [1,1,2,3,3-(2)H(5)]glycerol is the most cost-effective alternative to measure glycerol and triglyceride kinetics. Recycling of glycerol from glycolysis and gluconeogenesis may lead to incompletely labelled tracer molecules. Many existing methods for the measurement of glycerol isotopic enrichment involve the production of glycerol derivatives that result in fragmentation of the glycerol molecule after ionization. It would be favourable to measure the intact tracer molecule since incompletely labelled tracer molecules may be measured as fully labelled. The number of methods available to measure the intact tracer in biological samples is limited. The aim of this project was to develop a gas chromatography/mass spectrometry (GC/MS) method for glycerol enrichment that measures the intact glycerol backbone and is suitable for electron ionization (EI), which is widely available. A previously published method for N-methyl-N-[tert-butyldimethylsilyl]trifluoroacetamide (MTBSTFA) derivatization was significantly improved; we produced a stable derivative and increased recovery 27-fold in standards. We used the optimized MTBSTFA method in VLDL-triglyceride and found that further modification was required to take matrix effects into account. We now have a robust method to measure glycerol isotopic enrichment by GC/EI-MS that can be used to rule out the known problem of tracer recycling in studies of VLDL kinetics. Copyright (c) 2010 John Wiley & Sons, Ltd.
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| 4. |
- Marinou, Kyriakoula, et al.
(author)
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Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men.
- 2011
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In: The British journal of nutrition. - 1475-2662 .- 0007-1145. ; 105:6, s. 857-65
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Journal article (peer-reviewed)abstract
- Before the menopause, women are relatively protected against CVD compared with men. The reasons for this sex difference are not completely understood, but hepatic fatty acid metabolism may play a role. The present study aimed to investigate the utilisation of plasma NEFA by the liver and to determine whether they are partitioned differently into ketone bodies and VLDL-TAG in healthy, lean young men and women. Volunteers were studied during a prolonged overnight fast (12-19 h) using an intravenous infusion of [U-¹³C]palmitate. After 12 h fasting, the women had a more advantageous metabolic profile with lower plasma glucose (P < 0·05) and TAG (P < 0·05) but higher plasma NEFA (P < 0·05) concentrations. Plasma 3-hydroxybutyrate (3-OHB) concentrations rose more in women than in men, and the transfer of ¹³C from [U-¹³C]palmitate to plasma [¹³C]3-OHB reached a plateau 6-7 h after the start of the infusion in women but was still increasing at 6 h in men. This implies a slower 3-OHB production rate and/or dilution by other precursor pools in men. In women, the high isotopic enrichment of plasma 3-OHB suggested that systemic plasma fatty acids were the major source of 3-OHB production. However, in men, this was not observed during the course of the study (P < 0·01). There were no sex differences for the incorporation of ¹³C into VLDL1- or VLDL2-TAG. The ability of young women to partition fatty acids towards ketone body production rather than VLDL-TAG may contribute to their more advantageous metabolic profile compared with young men.
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| 5. |
- Risérus, Ulf, et al.
(author)
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Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men
- 2008
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 57:2, s. 332-339
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Journal article (peer-reviewed)abstract
- OBJECTIEVE-Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPAR delta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS-The PPAR delta agonist (10 mg o.d. GW501516), a comparator PPAR alpha agonist (20 mu g o.d. GW590735)), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS-Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (-30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO, directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS-The PPAR delta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.
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| 6. |
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| 7. |
- Westerbacka, Jukka, et al.
(author)
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Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease
- 2010
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In: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 139:6, s. 1961-1971.e1
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Journal article (peer-reviewed)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 [(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.
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