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.

scholarly journals The Effect of Fructose Feeding on Intestinal Triacylglycerol Production and De Novo Fatty Acid Synthesis in Humans

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1781
Author(s):  
Simon Steenson ◽  
Fariba Shojaee-Moradie ◽  
Martin B. Whyte ◽  
Kim G. Jackson ◽  
Julie A. Lovegrove ◽  
...  
Keyword(s):  
De Novo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Acute Effect ◽  
De Novo Lipogenesis ◽  
Fructose Intake ◽  
High Fructose ◽  
Catabolic Rate

A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (<2% energy) for 11 h. Oral 2H2O was administered to measure fasting and postprandial DNL. Postprandial chylomicron (CM)-TAG and very low-density lipoprotein (VLDL)-TAG kinetics were measured with an intravenous bolus of [2H5]-glycerol. CM and VLDL were separated by their apolipoprotein B content using antibodies. Plasma TAG (p < 0.005) and VLDL-TAG (p = 0.003) were greater, and CM-TAG production rate (PR, p = 0.046) and CM-TAG fractional catabolic rate (FCR, p = 0.073) lower when high-fructose was consumed, with no differences in VLDL-TAG kinetics. Insulin was lower (p = 0.005) and apoB48 (p = 0.039), apoB100 (p = 0.013) and non-esterified fatty acids (NEFA) (p = 0.013) were higher after high-fructose. Postprandial hepatic fractional DNL was higher than intestinal fractional DNL with high-fructose (p = 0.043) and low-fructose (p = 0.043). Fructose consumption had no effect on the rate of intestinal or hepatic DNL. We provide the first measurement of the rate of intestinal DNL in humans. Lower CM-TAG PR and CM-TAG FCR with high-fructose consumption suggests lower clearance of CM, rather than elevated production, may contribute to elevated plasma TAG, possibly due to lower insulin-mediated stimulation of lipoprotein lipase.

scholarly journals Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

2015 ◽  
Vol 112 (37) ◽  
pp. 11630-11635 ◽  
Author(s):  
Yan Wang ◽  
Markey C. McNutt ◽  
Serena Banfi ◽  
Michael G. Levin ◽  
William L. Holland ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Fed State ◽  
Beneficial Effects ◽  
Brown Adipose

Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3−/− mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3−/− animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3−/− mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target.

scholarly journals ChREBP Reciprocally Regulates Liver and Plasma Triacylglycerol Levels in Different Manners

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1699 ◽  
Author(s):  
Katsumi Iizuka ◽  
Ken Takao ◽  
Takehiro Kato ◽  
Yukio Horikawa ◽  
Jun Takeda
Keyword(s):  
Fatty Acid ◽  
Fluorescent Protein ◽  
De Novo ◽  
Density Lipoprotein ◽  
Plasma Free Fatty Acid ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Fatty Acid Elongase ◽  
Plasma Triacylglycerol

Carbohydrate response element-binding protein (ChREBP) has an important role in the carbohydrate-mediated regulation of hepatic de novo lipogenesis, but the mechanism for how it regulates plasma triacylglycerol (TAG) levels has not been established. This study aimed to clarify the role of ChREBP in regulation of plasma TAG levels. We analyzed the metabolic changes in mice infected with an adenovirus expressing ChREBP Δ196 (Ad-ChREBP). Compared with adenovirus harboring green fluorescent protein infected mice, Ad-ChREBP-infected mice had higher plasma free fatty acid levels and paradoxically lower plasma 3-hydroxybutyrate levels through decreased fatty acid oxidation, rather than ketogenesis. Consistent with their hepatomegaly and increased lipogenic gene expression, the liver TAG contents were much higher. Regarding lipid composition, C16:0 was much lower and C18:1n-9 was much higher, compatible with increased stearoyl CoA desaturase-1 and ELOVL fatty acid elongase 6 expression. Furthermore, Ad-ChREBP-infected mice had decreased plasma TAG and very low density lipoprotein (VLDL)-TAG levels, consistent with decreased Angiopoietin-like protein 3 (Angptl3) and increased fibroblast growth factor (Fgf21) mRNA and protein levels. Finally, Ad-ChREBP infection increased white adipose tissue Ucp1 mRNA levels with increased plasma Fgf21 levels. Because Fgf21 and Angptl3 are known to activate and suppress lipolysis in adipose tissues and oxidative tissues, ChREBP appears to regulate plasma TAG levels by modulating Fgf21 and Angptl3 levels. Thus, ChREBP overexpression led to dissociation of hepatic steatosis from hyperlipidemia.

scholarly journals Differences in partitioning of meal fatty acids into blood lipid fractions: a comparison of linoleate, oleate, and palmitate

2009 ◽  
Vol 296 (1) ◽  
pp. E64-E71 ◽  
Author(s):  
Leanne Hodson ◽  
Siobhán E. McQuaid ◽  
Fredrik Karpe ◽  
Keith N. Frayn ◽  
Barbara A. Fielding
Keyword(s):  
Fatty Acids ◽  
Test Meal ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Nonesterified Fatty Acid ◽  
Lipid Fractions ◽  
Functional Consequences ◽  
Single Meal

There has been much interest in the health effects of dietary fat, but few studies have comprehensively compared the acute metabolic fate of specific fatty acids in vivo. We hypothesized that different classes of fatty acids would be variably partitioned in metabolic pathways and that this would become evident over 24 h. We traced the fate of fatty acids using equal amounts of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate given in a test breakfast meal in 12 healthy subjects. There was a tendency for differences in the concentrations of the tracers in plasma chylomicron-triacylglycerol (TG) (oleate > palmitate > linoleate). This pattern remained in plasma nonesterified fatty acid (NEFA) and very low-density lipoprotein (VLDL)-TG ( P ≤ 0.01 and P ≤ 0.02 for [U-13C]oleate vs. both [U-13C]palmitate and [U-13C]linoleate for NEFA and VLDL-TG, respectively). There was significantly more [U-13C]linoleate than the other two tracers in plasma cholesteryl ester and phospholipid (PL). Using the values for isotopic enrichment in the different lipid fractions compared with the test meal, we calculated the contribution of meal fatty acids to the respective fractions. At 24 h, 10% of plasma PL-linoleate originated from the breakfast test meal. This was significantly greater than for oleate and palmitate (both 3 ± 0.3%; P < 0.05). This pattern was also true for erythrocyte PL fatty acids. The marked rapid incorporation of linoleate from a single meal into blood PL fractions may have functional consequences such as maintenance of membrane fluidity and may explain why linoleate is a useful biomarker of dietary intake.

Abstract 1189: Changes in the Prevalence of Abnormal Lipid Fractions among US Adults: Results from the National Health and Nutrition Examination Survey II, III, and 1999–2006

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jerome D Cohen ◽  
Mark J Cziraky ◽  
Terry A Jacobson ◽  
Anna Wallace ◽  
Cassie Cai
Keyword(s):  
National Health ◽  
Smoking Status ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
The Elderly ◽  
Lipoprotein Cholesterol ◽  
Health And Nutrition ◽  
Lipid Fractions ◽  
Prevalence Of Obesity

Objective To examine the prevalence of abnormal lipid fractions among US adults from 1976 through 2006, with a focus on the relationship of dyslipidemia and obesity. Methods Adults aged 20 to 74 years who took the blood lipid examination were selected from the National Health and Nutrition Examination Surveys (NHANES): NHANES II (1976 –1980), NHANES III (1988 –1994), and NHANES 1999 –2006. Obesity was defined as BMI ≥ 30 kg/m 2 . Dyslipidemia was defined as presence of one or more abnormal lipid fractions: low density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, high density lipoprotein cholesterol (HDL-C) < 40 mg/dL, and triglycerides (TG) ≥ 150 mg/dL. Crude and age-stratified proportions of abnormal lipid fractions for US adults and for those with obesity were estimated. Multivariate analysis was used to assess the association between dyslipidemia and obesity, controlling for age, gender, race/ethnicity, NHANES wave, and comorbidities (heart attack, diabetes and smoking status). Results The prevalence of abnormal LDL-C decreased from 43.5% in NHANES II to 36.3% in NHANES 1999–2006; however, during this period, the prevalence of abnormal TG and HDL-C combined doubled from 2.1% to 4.8% and the abnormal TG more than tripled within the elderly population (from 1.8% to 11.3%). It was estimated that antidyslipidemic medication use was less than 2.6% for adults with dyslipidemia throughout study period. With the increased prevalence of obesity between NHANES II and NHANES 1999 –2006, the prevalence of abnormal TG and HDL-C combined increased from 3.8% in NHANES II to 6.5% in NHANES 1999 –2006 within obese adults. Multivariate analyses of BMI with dyslipidemia were significant (p< 0.001). Adults with obesity were more likely to have dyslipidemia than those with BMI < 25 kg/m 2 [OR=2.9, (95% CI: 2.7–3.2)]. Conclusions Prevalence of abnormal TG and/or HDL-C increased between NHANES II and NHANES 1999–2006 although the abnormal LDL-C shows an optimistic trend. This was paralleled by a shift in the distribution of BMI toward the obese category. As the US population is aging and becoming more obese, this analysis underscores the need for renewed public health efforts with focus on treating multiple abnormal lipid fractions and preventing dyslipidemia via body mass control.

scholarly journals Hepatic De Novo Lipogenesis in Obese Youth Is Modulated by a Common Variant in the GCKR Gene

2015 ◽  
Vol 100 (8) ◽  
pp. E1125-E1132 ◽  
Author(s):  
Nicola Santoro ◽  
Sonia Caprio ◽  
Bridget Pierpont ◽  
Michelle Van Name ◽  
Mary Savoye ◽  
...  
Keyword(s):  
Glucose Oxidation ◽  
De Novo ◽  
Liver Lipid ◽  
Low Density Lipoprotein ◽  
Lipid Synthesis ◽  
Area Under The Curve ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Obese Youth ◽  
Lower Ability

Objective: This study's aim was to evaluate whether the GCKR rs1260326 variant increases hepatic de novo lipogenesis (DNL). Setting and Design: To test this hypothesis, 14 adolescents, seven homozygous for the common allele (CC) and seven homozygous for the risk allele (TT), underwent measurement of hepatic DNL during the fasting state and after consumption of a carbohydrate (CHO) drink (75 g glucose and 25 g fructose). DNL was assessed through incorporation of deuterium in the palmitate contained in the very low-density lipoprotein. Results: Subjects with TT demonstrated higher fasting fractional DNL (P = .036) and a lower increase in fractional DNL after the CHO challenge (P = .016). With regard to absolute lipogenesis, TT subjects had both higher fasting rates (P = .015) and 44% greater area under the curve of absolute lipogenesis during the study (P = .016), compared to CC subjects. Furthermore, subjects carrying the TT genotype showed higher basal rates of glucose oxidation (P = .0028) and a lower ability than CC subjects to increase the rates of glucose oxidation after the CHO load (P = .054). Conclusions: This study reports for the first time rates of DNL in obese adolescents and suggests that the GCKR rs1260326 gene variant, which is associated with greater glycolysis, increases hepatic DNL. These data highlight the role of glycolytic carbon flux in liver lipid synthesis and hypertriglyceridemia in these youngsters.

THE LIPID COMPOSITION OF ERYTHROCYTE MEMBRANES AND PLASMA LIPOPROTEINS IN "DOUBLE-MUSCLED" CATTLE

1982 ◽  
Vol 62 (4) ◽  
pp. 1089-1100 ◽  
Author(s):  
J. A. BASARAB ◽  
R. T. BERG ◽  
J. R. THOMPSON
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Total Lipid ◽  
Lipid Composition ◽  
Lipid Fraction ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Lipoproteins ◽  
Erythrocyte Membranes ◽  
Lipid Fractions

The lipid composition of erythrocyte membranes was determined in 11 phenotypically extreme- and 11 normal-muscled cattle of a "double-muscled" (DM) breed group. The relative concentrations of lipid classes in erythrocyte membranes from extreme- and normal-muscled DM cattle were similar. Significant differences were observed in the relative concentrations of individual fatty acids in the erythrocyte membrane sphingomyelin and phosphatidylethanolamine fractions from extreme-compared with normal-muscled DM cattle. The most notable differences were a higher (P < 0.05) concentration of palmitic acid and a lower (P < 0.01) concentration of oleic acid in sphingomyelin from extreme-muscled DM cattle. In a second study, the total lipid composition of plasma, plasma high density lipoprotein (HDL) and plasma low plus very low density lipoprotein (LDL-VLDL) fractions was determined in six extreme- and six normal-muscled DM cattle. Extreme-muscled DM cattle had a lower (P < 0.05) concentrations of triacylglycerols in all three total lipid fractions and higher (P < 0.05) concentrations of cholesterol in plasma and cholesterol esters in the LDL-VLDL total lipid fraction as compared with normal-muscled DM cattle. The concentration of lysophosphatidylcholine was higher (P < 0.05) in the LDL-VLDL total lipid fraction from extreme-muscled DM cattle, but no other differences in the relative amounts of the phospholipids were observed. Extreme-muscled DM cattle had higher (P < 0.05) concentrations of polyunsaturated fatty acids in the plasma and LDL-VLDL total lipid fractions, with a similar trend occurring in the HDL total lipid fraction. The results of the first study demonstrate a change in fatty acid composition of the membrane, while those of the second indicate an increased rate of VLDL metabolism and/or lower rates of adipose fatty acid turnover in extreme- compared with normal-muscled DM cattle. Key words: Lipid composition, lipoproteins, double muscled cattle

scholarly journals Modification of fatty acid composition of polar and neutral lipids of blood and liver in rat in conditions of prolonged high-fat diet

2013 ◽  
Vol 59 (6) ◽  
pp. 644-654 ◽  
Author(s):  
T.P. Novgorodtseva ◽  
Yu.K. Karaman ◽  
N.V. Zhukova
Keyword(s):  
Fatty Acids ◽  
High Fat Diet ◽  
Prolonged Exposure ◽  
De Novo ◽  
Neutral Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Fat ◽  
Lipid Fractions

Studied the composition of fatty acids of polar and neutral lipids of plasma, erythrocytes and liver Wistar rats under prolonged high-fat diet. It was established that during long-term (90-180 days) in rats high-fat load is blocking the cells ligand-retseptor active capture polyunsaturated fatty acids (PUFAs) in the low-density lipoprotein (LDL). This is confirmed by the accumulation of blood in LDL cholesterol and lipid fractions, esterified n-3 and n-6 PUFA (triacylglycerides, sterols esters, phospholipids), while the deficit these same fatty acids in the lipids of erythrocytes. In the liver under the influence of prolonged high-fat diet increased pool monoenic (18:1 n-9) and polyunsaturated (20:5 n-3, 20:3 n-6, 22:5 n-3) fatty acids. These data suggest that prolonged exposure of rats high-fat diet contributes to compensatory de novo synthesis of fatty acids in the liver. However, due to violations of the receptor active transport of fatty acids synthesized in the liver fatty acids are not captured by cells of the peripheral organs. Identified data allow us to expand the understanding of the role of nutritional factors in the physiology and pathophysiology of the cell, modulation of lipid metabolism.

scholarly journals A Dual Sugar Challenge Test for Lipogenic Sensitivity to Dietary Fructose

2011 ◽  
Vol 96 (3) ◽  
pp. 861-868 ◽  
Author(s):  
Lisa C. Hudgins ◽  
Thomas S. Parker ◽  
Daniel M. Levine ◽  
Marc K. Hellerstein
Keyword(s):  
De Novo ◽  
Low Density Lipoprotein ◽  
Challenge Test ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Dose Effect ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Repeated Doses ◽  
Dietary Sugar

Context: Increased hepatic de novo lipogenesis (DNL) in response to dietary sugar is implicated in dyslipidemia, fatty liver, and insulin resistance. Objective: The aim of the study was to develop a simple outpatient tolerance test for lipogenic sensitivity to dietary sugar. Design and Setting: In inpatients given repeated doses of fructose, protocol 1 compared the acute increase in DNL determined from the percentage of palmitate (“new palmitate”) and the percentage of isotopically labeled palmitate (“%DNL”) in very low-density lipoprotein triglyceride (TG). Protocol 2 compared the increase in new palmitate in outpatients given three different sugar beverages in a randomized crossover design. Participants: There were 15 lean and overweight volunteers in protocol 1 and 15 overweight volunteers in protocol 2. Interventions: In protocol 1, subjects received 1.4 g/kg fructose in divided oral doses over 6 h; in protocol 2, subjects received 0.5 g/kg fructose, 0.5 g/kg fructose plus 0.5g/kg glucose, or 1 g/kg fructose plus 1g/kg glucose each as a single oral bolus. Main Outcome Measures: We measured the increase in DNL by two methods. Results: After repeated doses of fructose, new palmitate was significantly correlated with the increase in %DNL (Δ, r = 0.814; P &lt; 0.001) and with fasting insulin levels (area under the curve, r = 0.754; P = 0.001). After a single sugar dose, new palmitate showed a dose effect and was greater after fructose plus glucose. Very low-density lipoprotein TG and total TG significantly increased in both protocols. Conclusions: A single oral bolus of fructose and glucose rapidly increases serum TG and TG palmitate in overweight subjects. A dual sugar challenge test could prove useful to identify individuals at risk for carbohydrate-induced dyslipidemia and other adverse effects of increased DNL.

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