scholarly journals Dose-dependent quantitative effects of acute fructose administration on hepatic de novo lipogenesis in healthy humans

2018 ◽  
Vol 315 (1) ◽  
pp. E126-E132 ◽  
Author(s):  
Carine Beysen ◽  
Marcella Ruddy ◽  
Aubrey Stoch ◽  
Lori Mixson ◽  
Kimberly Rosko ◽  
...  
Keyword(s):  
De Novo ◽  
Density Lipoprotein ◽  
Fat Free Mass ◽  
De Novo Lipogenesis ◽  
High Dose ◽  
Distribution Analysis ◽  
Nonalcoholic Fatty Liver ◽  
Healthy Humans ◽  
Mass Isotopomer Distribution Analysis ◽  
Subject Variability

Fructose feeding increases hepatic de novo lipogenesis (DNL) and is associated with nonalcoholic fatty liver disease. Little is known, however, about individual variation in susceptibility to fructose stimulation of DNL. In this three-period crossover study, 17 healthy male subjects were enrolled to evaluate the within- and between-subject variability of acute fructose feeding on hepatic fractional DNL. During each assessment, [1-13C1]acetate was infused to measure DNL in the fasting state and during fructose feeding. Subjects randomly received a high dose of fructose (10 mg·kg fat-free mass−1·min−1) on two occasions and a low dose (5 mg·kg fat-free mass−1·min−1) on another. Fructose solutions were administered orally every 30 min for 9.5 h. Ten subjects completed all three study periods. DNL was assessed as the fractional contribution of newly synthesized palmitate into very-low-density lipoprotein triglycerides using mass isotopomer distribution analysis. Mean fasting DNL was 5.3 ± 2.8%, with significant within- and between-subject variability. DNL increased dose dependently during fructose feeding to 15 ± 2% for low- and 29 ± 2% for high-dose fructose. The DNL response to high-dose fructose was very reproducible within an individual ( r = 0.93, P < 0.001) and independent of fasting DNL. However, it was variable between individuals and significantly correlated to influx of unlabeled acetyl-CoA ( r = 0.7, P < 0.001). Unlike fasting DNL, fructose-stimulated DNL is a robust and reproducible measure of hepatic lipogenic activity for a given individual and may be a useful indicator of metabolic disease susceptibility and treatment response.

Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O

2004 ◽  
Vol 286 (4) ◽  
pp. E577-E588 ◽  
Author(s):  
A. Strawford ◽  
F. Antelo ◽  
M. Christiansen ◽  
M. K. Hellerstein
Keyword(s):  
Cell Proliferation ◽  
Adipose Tissue ◽  
Half Life ◽  
De Novo ◽  
Human Subjects ◽  
De Novo Lipogenesis ◽  
Gas Chromatography Mass Spectrometry ◽  
Distribution Analysis ◽  
Mass Isotopomer Distribution Analysis

The turnover of adipose tissue components (lipids and cells) and the pathways of adipose lipid deposition have been difficult to measure in humans. We apply here a 2H2O long-term labeling technique for concurrent measurement of adipose-triglyceride (TG) turnover, cell (DNA) proliferation, and de novo lipogenesis (DNL). Healthy subjects drank 2H2O (70 ml/day) for 5-9 wk. Subcutaneous adipose tissue aspirates were taken (gluteal, thigh, and flank depots). Deuterium incorporation into TG glycerol (representing all-source TG synthesis), TG palmitate (representing DNL, by mass isotopomer distribution analysis), and DNA (representing cell proliferation) was measured by gas chromatography-mass spectrometry. Subjects tolerated the protocol well, and body 2H2O enrichments were stable. Mean TG-glycerol fractional synthesis was 0.12 (i.e., 12%) with a range of 0.03-0.32 after 5 wk and 0.20 (range 0.08-0.49) after 9 wk (TG half-life 200-270 days). Label decay measurements 5-8 mo after discontinuing 2H2O gave similar turnover estimates. Net lipolysis (TG turnover) was 50-60 g/day. DNL contribution to adipose-TG was 0.04 after 9 wk, representing ∼20% of newly deposited TG. Cell proliferation was 0.10-0.17 after 9 wk (half-life 240-425 days). In summary, long-term 2H2O administration to human subjects allows measurement of the dynamics of adipose tissue components. Turnover of all elements is slow, and DNL contributes ∼20% of new TG.

scholarly journals Effects of isoenergetic overfeeding of either carbohydrate or fat in young men

2000 ◽  
Vol 84 (2) ◽  
pp. 233-245 ◽  
Author(s):  
Ole Lammert ◽  
Niels Grunnet ◽  
Peter Faber ◽  
Kirsten Schroll Bjørnsbo ◽  
John Dich ◽  
...  
Keyword(s):  
Fat Mass ◽  
De Novo ◽  
Fat Free Mass ◽  
Whole Body ◽  
Distribution Analysis ◽  
Mass Isotopomer Distribution Analysis ◽  
The Difference ◽  
Normal Men ◽  
Plasma Leptin ◽  
Mass Increase

Ten pairs of normal men were overfed by 5 MJ/d for 21 d with either a carbohydrate-rich or a fat-rich diet (C- and F-group). The two subjects in each pair were requested to follow each other throughout the day to ensure similar physical activity and were otherwise allowed to maintain normal daily life. The increase in body weight, fat free mass and fat mass showed great variation, the mean increases being 1·5 kg, 0·6 kg and 0·9 kg respectively. No significant differences between the C- and F-group were observed. Heat production during sleep did not change during overfeeding. The RQ during sleep was 0·86 and 0·78 in the C- and F-group respectively. The accumulated faecal loss of energy, DM, carbohydrate and protein was significantly higher in the C- compared with the F-group (30, 44, 69 and 51 % higher respectively), whereas the fat loss was the same in the two groups. N balance was not different between the C- and F-group and was positive. Fractional contribution from hepatic de novo lipogenesis, as measured by mass isotopomer distribution analysis after administration of [1-13C]acetate, was 0·20 and 0·03 in the C-group and the F-group respectively. Absolute hepatic de novo lipogenesis in the C-group was on average 211 g per 21 d. Whole-body de novo lipogenesis, as obtained by the difference between fat mass increase and dietary fat available for storage, was positive in six of the ten subjects in the C-group (mean 332 (SEM 191) g per 21 d). The change in plasma leptin concentration was positively correlated with the change in fat mass. Thus, fat storage during overfeeding of isoenergetic amounts of diets rich in carbohydrate or in fat was not significantly different, and carbohydrates seemed to be converted to fat by both hepatic and extrahepatic lipogenesis.

scholarly journals Cholesterol Synthesis and De Novo Lipogenesis in Premature Infants Determined by Mass Isotopomer Distribution Analysis

2004 ◽  
Vol 56 (4) ◽  
pp. 602-607 ◽  
Author(s):  
Lorraine N Renfurm ◽  
Robert H J Bandsma ◽  
Henkjan J Verkade ◽  
Christiaan V Hulzebos ◽  
Theo van Dijk ◽  
...  
Keyword(s):  
Premature Infants ◽  
Cholesterol Synthesis ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Distribution Analysis ◽  
Isotopomer Distribution ◽  
Mass Isotopomer Distribution Analysis ◽  
Mass Isotopomer

scholarly journals In VivoLipid Regulation Mechanism of Polygoni Multiflori Radix in High-Fat Diet Fed Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pei Lin ◽  
Yan Ran He ◽  
Jian Mei Lu ◽  
Na Li ◽  
Wan Gen Wang ◽  
...  
Keyword(s):  
De Novo ◽  
Hepatic Lipase ◽  
Liver Lipid ◽  
Density Lipoprotein ◽  
Positive Control ◽  
Synthesis Rate ◽  
High Dose ◽  
Regulation Mechanism ◽  
Nonalcoholic Fatty Liver ◽  
Medium Dose

Mechanisms of the water extracts of Polygoni Multiflori Radix (PMR) and its processed products (PMRP) on liver lipid metabolism were observed in this paper. Aqueous extract of PMR and PMRP was given to nonalcoholic fatty liver model rats, respectively. PMR was better in reducing the contents of very low density lipoprotein (VLDL) than PMRP and the positive control groups. In the aspect of regulating TG, medium dose PMR reduced the activity of diacylglycerol acyltransferase (DGAT) to1536±47.69 pg/mL (P<0.001) and promoted the expression of hepatic lipase (HL) to23.59±0.2758 U/mL (P<0.05). HL promotion ability of medium dose PMR was similar with the simvastatin positive control. Both medium and high dose of PMR showed significant alterations in TC, which were related to the downregulation effects on hydroxyl methyl-glutaryl coenzyme A reductase (HMGCR) and upregulation effects on cholesterol 7-alpha-hydroxylase or cytochrome P450 7A (CYP7A). Quantitative relationships research indicated that the prominent effect on inhibiting the content of HMGCR (r=0.756,P<0.05) was strongly positive correlated with to the TC regulation effects. Effects of PMR on enhancing decomposition rate or reducingde novosynthesis rate of TG and TC were better than PMRP.

Model for measuring absolute rates of hepatic de novo lipogenesis and reesterification of free fatty acids

1993 ◽  
Vol 265 (5) ◽  
pp. E814-E820 ◽  
Author(s):  
M. K. Hellerstein ◽  
R. A. Neese ◽  
J. M. Schwarz
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
De Novo ◽  
Human Subjects ◽  
Fat Oxidation ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Distribution Analysis ◽  
Oxidation Rates ◽  
Mass Isotopomer Distribution Analysis

We have previously presented a precursor-product stable isotopic technique for measuring in vivo the fraction of very low-density lipoprotein-fatty acids (VLDL-FA) derived from de novo lipogenesis (fractional DNL). Here, we propose a technique for converting fractional DNL into absolute rates of DNL and describe its explicit underlying assumptions. The technique combines the fractional DNL method with a modification of the method of S. Klein, V. R. Young, G. L. A. Blackburn, B. R. Bistrain, and R. R. Wolfe (J. Clin. Invest. 78: 928-933, 1986), for estimating hepatic reesterification of free fatty acids (FFA). Infusions of [1,2,3,4-13C]palmitate and [1-13C]acetate are performed concurrently with indirect calorimetry in human subjects. Fractional DNL (based on mass isotopomer distribution analysis of VLDL-FA), the rate of appearance of plasma FFA (Ra of FFA), and net fat oxidation in the whole body are measured. Equations from the hepatic reesterification model, modified to include the contribution from DNL, allow calculation of absolute DNL (= fractional DNL x [Ra of FFA - net whole body fat oxidation], when respiratory quotient < 1.0). Sample results from human subjects with different dietary energy intakes are presented, with calculations of absolute DNL, absolute reesterification, and absolute fat oxidation rates. The assumptions of this technique (in particular, that all fat oxidized is derived at steady state from circulating FFA and that DNL and reesterification of FFA both occur exclusively in liver) are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Carrot Supplementation Improves Blood Pressure and Reduces Aortic Root Lesions in an Atherosclerosis-Prone Genetic Mouse Model

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1181
Author(s):  
Raffaella Soleti ◽  
Marine Coué ◽  
Charlotte Trenteseaux ◽  
Gregory Hilairet ◽  
Lionel Fizanne ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mouse Model ◽  
Aortic Root ◽  
De Novo ◽  
Body Weight Gain ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Hemodynamic Parameters ◽  
Cellular Models ◽  
Genetic Mouse Model

Epidemiological studies have shown that carrot consumption may be associated with a lower risk of developing several metabolic dysfunctions. Our group previously determined that the Bolero (Bo) carrot variety exhibited vascular and hepatic tropism using cellular models of cardiometabolic diseases. The present study evaluated the potential metabolic and cardiovascular protective effect of Bo, grown under two conditions (standard and biotic stress conditions (BoBS)), in apolipoprotein E-knockout (ApoE−/−) mice fed with high fat diet (HFD). Effects on metabolic/hemodynamic parameters and on atherosclerotic lesions have been assessed. Both Bo and BoBS decreased plasma triglyceride and expression levels of genes implicated in hepatic de novo lipogenesis and lipid oxidation. BoBS supplementation decreased body weight gain, secretion of very-low-density lipoprotein, and increased cecal propionate content. Interestingly, Bo and BoBS supplementation improved hemodynamic parameters by decreasing systolic, diastolic, and mean blood pressure. Moreover, Bo improved cardiac output. Finally, Bo and BoBS substantially reduced the aortic root lesion area. These results showed that Bo and BoBS enriched diets corrected most of the metabolic and cardiovascular disorders in an atherosclerosis-prone genetic mouse model and may therefore represent an interesting nutritional approach for the prevention of cardiovascular diseases.

scholarly journals Concepts and Treatment Approaches in Nonalcoholic Fatty Liver Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dina L. Halegoua-De Marzio ◽  
Jonathan M. Fenkel
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Imaging Techniques ◽  
De Novo Lipogenesis ◽  
Central Adiposity ◽  
Preventative Care ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) affects up to 30% of adults and is the most common liver disease in Western nations. NAFLD is associated with central adiposity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, and cardiovascular disease. It encompasses the entire spectrum of fatty liver diseases from simple steatosis to nonalcoholic steatohepatitis (NASH) with lobular/portal inflammation, hepatocellular necrosis, and fibrosis. Of those who develop NASH, 15–25% will progress to end stage liver disease and hepatocellular carcinoma over 10–20 years. Its pathogenesis is complex, and involves a state of lipid accumulation due to increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, and increased incidence of de novo lipogenesis. Plasma aminotransferases and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for definitive diagnosis. Many new plasma biomarkers and imaging techniques are now available that should improve the ability to diagnose NAFLD noninvasively Due to its complexity and extrahepatic complications, treatment of NAFLD requires a multidisciplinary approach with excellent preventative care, management, and treatment. This review will evaluate our current understanding of NAFLD, with a focus on existing therapeutic approaches and potential pharmacological developments.

scholarly journals Regular exercise potentiates energetically expensive hepatic de novo lipogenesis during early weight regain

2019 ◽  
Vol 317 (5) ◽  
pp. R684-R695
Author(s):  
David M. Presby ◽  
L. Allyson Checkley ◽  
Matthew R. Jackman ◽  
Janine A. Higgins ◽  
Kenneth L. Jones ◽  
...  
Keyword(s):  
Weight Loss ◽  
Energy Expenditure ◽  
De Novo ◽  
Energy Gap ◽  
Cholesterol Biosynthesis ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Positive Energy ◽  
Hepatic Expression ◽  
Expression Of Genes

Exercise is a potent facilitator of long-term weight loss maintenance (WLM), whereby it decreases appetite and increases energy expenditure beyond the cost of the exercise bout. We have previously shown that exercise may amplify energy expenditure through energetically expensive nutrient deposition. Therefore, we investigated the effect of exercise on hepatic de novo lipogenesis (DNL) during WLM and relapse to obesity. Obese rats were calorically restricted with (EX) or without (SED) treadmill exercise (1 h/day, 6 days/wk, 15 m/min) to induce and maintain weight loss. After 6 wk of WLM, subsets of WLM-SED and WLM-EX rats were allowed ad libitum access to food for 1 day to promote relapse (REL). An energy gap-matched group of sedentary, relapsing rats (REL-GM) were provided a diet matched to the positive energy imbalance of the REL-EX rats. During relapse, exercise increased enrichment of hepatic DN-derived lipids and induced hepatic molecular adaptations favoring DNL compared with the gap-matched controls. In the liver, compared with both REL-SED and REL-GM rats, REL-EX rats had lower hepatic expression of genes required for cholesterol biosynthesis; greater hepatic expression of genes that mediate very low-density lipoprotein synthesis and secretion; and greater mRNA expression of Cyp27a1, which encodes an enzyme involved in the biosynthesis of bile acids. Altogether, these data provide compelling evidence that the liver has an active role in exercise-mediated potentiation of energy expenditure during early relapse.

scholarly journals Fasting hepatic de novo lipogenesis is not reliably assessed using circulating fatty acid markers

2019 ◽  
Vol 109 (2) ◽  
pp. 260-268 ◽  
Author(s):  
Fredrik Rosqvist ◽  
Catriona A McNeil ◽  
Camilla Pramfalk ◽  
Sion A Parry ◽  
Wee Suan Low ◽  
...  
Keyword(s):  
Fatty Acid ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
De Novo Lipogenesis ◽  
Deuterated Water ◽  
Lipid Fractions ◽  
Habitual Diet ◽  
Fa Markers

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 2H2O (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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