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 Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes

2021 ◽  
Vol 22 (14) ◽  
pp. 7452
Author(s):  
Samuel Furse ◽  
Denise S. Fernandez-Twinn ◽  
Davide Chiarugi ◽  
Albert Koulman ◽  
Susan E. Ozanne
Keyword(s):  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Time Course ◽  
De Novo ◽  
Lipid Analysis ◽  
Temporal Distribution ◽  
De Novo Lipogenesis ◽  
Analysis Tool

The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus (GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams’ systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.

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.

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.

Abstract 052: Direct Correlation Between Blood Pressure and Nephron Endowment in a Genetic Mouse Model of Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sean P Didion ◽  
Xuexiang Wang ◽  
Michael R Garrett
Keyword(s):  
Blood Pressure ◽  
Mouse Model ◽  
Systolic Blood Pressure ◽  
Inbred Strains ◽  
Nephron Number ◽  
Control Blood Pressure ◽  
Nephron Endowment ◽  
Genetic Mouse Model ◽  
Progressive Loss ◽  
Inbred Strains Of Mice

Blood pressure high (BPH2) mice represent a novel genetic mouse model of hypertension that was derived from an 8-way cross of common inbred strains of mice. Mice derived from the original cross were segregated by blood pressure and then inbred to establish distinct mouse lines including the BPH2 line, a normotensive genetic control (blood pressure normal; BPN3) as well as a blood pressure low (BPL1) line. The goal of the present study was to test the hypothesis that the level of blood pressure in BPH2, BPN3, BPL1, and C57Bl/6 (normotensive inbred control) mice correlates with nephron endowment. Systolic blood pressure (SBP) was measured in male BPH2, BPN3, BPL1, and C57BL/6 mice (n=6/group) using tail-cuff plethysmography. SBP in BPH2, BPN3, BPL1, and C57BL/6 mice averaged 152±2, 117±1; 105±4; and 107±3 mm Hg, respectively. SBP was significantly greater (P<0.05) in BPH2 mice compared to the other three groups of mice. In contrast, SBP was found to be similar (P>0.05) between BPL1 and C57BL/6 mice and significantly (P<0.05) lower than that in either BPH2 or BPN3 mice. Total kidney weight/body weight ratios were found to be similar (P>0.05) in BPH2 and BPN3 mice and significantly (P<0.05) higher than that in BPL1 and C57BL/6 mice. Nephron number as assessed by the acid maceration technique revealed that total nephron number in BPH2, BPN3, BPL1, and C57Bl/6 averaged 10,409±285, 25,333±478, 27,300±445 and 22,533±668 nephrons per kidney, respectively. There was an extremely significant correlation (R2=0.779; P<0.0001) between nephron number and systolic blood pressure. These data provide evidence that blood pressure in a genetic mouse model of hypertension correlates with total nephron number. These findings are consistent with the emerging concept that nephron endowment at birth or progressive loss of nephrons with age or disease directly impacts blood pressure. Thus, we suggest that the BPH2 mouse can serve as an important experimental model to investigate the intrinsic relationship between nephron endowment and blood pressure.

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.

LXR inverse agonists inhibit de novo lipogenesis and reduce intestinal lipid and cholesterol absorption in a NAFLD mouse model

2018 ◽  
Vol 68 ◽  
pp. S353-S354
Author(s):  
C. Kremoser ◽  
U. Deuschle ◽  
C. Gege ◽  
O. Kinzel ◽  
H.D. Krol ◽  
...  
Keyword(s):  
Mouse Model ◽  
De Novo ◽  
Cholesterol Absorption ◽  
De Novo Lipogenesis ◽  
Inverse Agonists

scholarly journals Meeting Sugar Intake Recommendation Is Protective Against Health Parameters Associated With Chronic Disease in College Students

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 617-617
Author(s):  
April Callister ◽  
David Aguilar
Keyword(s):  
College Students ◽  
Plasma Lipids ◽  
De Novo ◽  
Undergraduate Research ◽  
Density Lipoprotein ◽  
Positive Association ◽  
De Novo Lipogenesis ◽  
Positive Trend ◽  
Central Adiposity ◽  
Sugar Consumption

Abstract Objectives Metabolic Syndrome (MetS) is an accumulation of health factors that increase an individual's chance of chronic diseases and disabling conditions, such as type II diabetes, heart attack, and stroke. Multiple studies have shown a positive association between sugar consumption and aggravation of parameters related to MetS. We analyzed the effects of meeting the acceptable macronutrient range (AMDR) for sugar consumption on MetS parameters among college students. We hypothesized that meeting this recommendation would be associated with positive outcomes for MetS parameters. Methods Plasma lipids, glucose, and waist circumference (WC) were measured in 167 Weber State Students (ages 18–65). A two-day diet record was collected and analyzed using diet and wellness plus. Participants were separated into two groups, based on whether or not they met the AMDR of consuming less than 25% of total calories from sugar. Mean comparisons between low sugar (LS) and high sugar (HS) consumers were performed using independent samples t-test. Results 63% of participants met the sugar AMDR recommendation. LS group participants presented lower WC (75.8 ± 10.5 vs. 75.5 ± 11.5 cm, P = 0.03) and plasma triglycerides (TG) (76.0 ± 47.6 vs. 121.6 ± 99.9 mg/dL, P = 0.001) compared to their HS counterparts. In addition, we observed a positive trend in the high-density lipoprotein cholesterol (HDL-C) (52.7 ± 16.9 vs 47.59 ± 17.14, P = 0.06) levels of the HS group, compared to the LS group. Conclusions We observed that the percentage of total calories consumed from sugar is an important modulator of circulating triglycerides and central adiposity. This is in accordance with previous studies, which show that excess fructose consumption exerts adipogenic effects, and can trigger de novo lipogenesis in the liver, resulting in increased triglyceride production and secretion. Funding Sources Weber State University Office of Undergraduate Research.

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