scholarly journals Sex Differences in Hepatic De Novo Lipogenesis with Acute Fructose Feeding

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1263 ◽  
Author(s):  
Wee Low ◽  
Thomas Cornfield ◽  
Catriona Charlton ◽  
Jeremy Tomlinson ◽  
Leanne Hodson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
De Novo ◽  
Dietary Fatty Acid ◽  
De Novo Lipogenesis ◽  
Liver Fat ◽  
Acid Oxidation ◽  
Free Sugars ◽  
Isotope Tracer ◽  
High Fructose

Dietary free sugars have received much attention over the past few years. Much of the focus has been on the effect of fructose on hepatic de novo lipogenesis (DNL). Therefore the aim of the present study was to investigate the effects of meals high and low in fructose on postprandial hepatic DNL and fatty acid partitioning and dietary fatty acid oxidation. Sixteen healthy adults (eight men, eight women) participated in this randomised cross-over study; study days were separated by a 4-week wash-out period. Hepatic DNL and dietary fatty acid oxidation were assessed using stable-isotope tracer methodology. Consumption of the high fructose meal significantly increased postprandial hepatic DNL to a greater extent than consumption of the low fructose meal and this effect was evident in women but not men. Despite an increase in hepatic DNL, there was no change in dietary fatty acid oxidation. Taken together, our data show that women are more responsive to ingestion of higher amounts of fructose than men and if continued over time this may lead to changes in hepatic fatty acid partitioning and eventually liver fat content.

scholarly journals Treatment with a polyherbal extract improves fat metabolism, attenuates hepatic stellate cell activation and fibrogenesis.

2021 ◽  
Author(s):  
Pavan Kumar Bellamakondi ◽  
Rizwan Baig Mirza ◽  
Onkar Murthy Mallappa ◽  
Azeemuddin Mohammed ◽  
Hariprasad VR ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cell Activation ◽  
De Novo ◽  
Stellate Cell ◽  
Stellate Cells ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Polyherbal Formulation

Non-alcoholic steatohepatitis (NASH) involves dysregulations in denovo lipogenesis, fatty acid oxidation, and fibrogenesis. Targeting these pathways holds promise for the treatment of liver disorders. Here we test the extract of a polyherbal formulation (namely Liv.52), which is approved by the Government of India's Drug Regulatory Authority - AYUSH. The current study evaluates the effect of Liv.52 on denovo lipogenesis, fatty acid oxidation, and fibrogenesis. Both in vivo and in vitro model systems were employed to evaluate the efficacy of this polyherbal formulation. Male Wistar rats were dosed with Liv.52 for 2 weeks (250mg/k.g) and expression levels of the genes involved in de novo lipogenesis and fatty acid oxidation pathways were analysed by quantitative real time PCR. Liv.52 treatment resulted in increased hepatic fatty acid oxidation and decreased de novo lipogenesis in these rats. It also reduced hepatic stellate cell activation in CCL4 treated Wistar rats as evidenced by histological evaluation. For in vitro experiments, HepG2 cells were cultured under lipotoxic conditions (using 200 micro molar palmitic acid) and the conditioned media from these cells were used for inducing activation and fibrogenesis in human hepatic stellate cells (HHSteC). Treatment with lipotoxic conditioned media resulted in activation of hepatic stellate cells and fibrogenesis, as evidenced by increased expression of alpha-smooth muscle actin (alpha-SMA), and desmin (markers of stellate cell activation) and increased levels of collagen and lumican (markers of fibrogenesis). Treatment with Liv.52 reversed the up-regulation of alpha-SMA, collagen and lumican levels in HHSteC cells. These results indicate that Liv.52 exerts its hepatoprotective effect by improving fatty acid metabolism and fibrogenesis.

scholarly journals Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang R. Lee ◽  
Jun H. Heo ◽  
Seong Lae Jo ◽  
Globinna Kim ◽  
Su Jung Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Membrane Component ◽  
Markers Of Inflammation ◽  
Receptor Membrane

AbstractObesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Hence, we focused on the role of cardiac Pgrmc1 in basal (Resting), glucose-dominant (Refed) and lipid-dominant high-fat diet (HFD) conditions. Pgrmc1 KO mice showed high FFA levels and low glucose levels compared to wild-type (WT) mice. Pgrmc1 KO mice presented low number of mitochondrial DNA copies in heart, and it was concomitantly observed with low expression of TCA cycle genes and oxidative phosphorylation genes. Pgrmc1 absence in heart presented low fatty acid oxidation activity in all conditions, but the production of acetyl-CoA and ATP was in pronounced suppression only in HFD condition. Furthermore, HFD Pgrmc1 KO mice resulted in high cardiac fatty acyl-CoA levels and TG level. Accordingly, HFD Pgrmc1 KO mice were prone to cardiac lipotoxicity, featuring high levels in markers of inflammation, endoplasmic reticulum stress, oxidative stress, fibrosis, and heart failure. In vitro study, it was also confirmed that Pgrmc1 enhances rates of mitochondrial respiration and fatty acid oxidation. This study is clinically important because mitochondrial defects in Pgrmc1 KO mice hearts represent the late phase of cardiac failure.

scholarly journals Differences between men and women in markers of dietary fatty acid oxidation

2015 ◽  
Author(s):  
Catriona McNeil ◽  
Camilla Pramfalk ◽  
Michael Pavlides ◽  
Fredrik Karpe ◽  
Leanne Hodson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Dietary Fatty Acid ◽  
Acid Oxidation ◽  
Men And Women

scholarly journals Cynanchum atratum Alleviates Non-Alcoholic Fatty Liver by Balancing Lipogenesis and Fatty Acid Oxidation in a High-Fat, High-Fructose Diet Mice Model

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 23
Author(s):  
Jing-Hua Wang ◽  
Seung-Ju Hwang ◽  
Dong-Woo Lim ◽  
Chang-Gue Son
Keyword(s):  
Fatty Acid ◽  
Fatty Liver ◽  
Fatty Acid Oxidation ◽  
The Body ◽  
Acid Oxidation ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
High Fructose Diet ◽  
High Fructose ◽  
Tnf Α

Cynanchum atratum, a medicinal herb, is traditionally used as an antidote, diuretic, and antipyretic in eastern Asia. The current study aimed to investigate the anti-fatty liver capacity of the ethanol extract of Cynanchum atratum (CAE) using a 10-week high-fat, high-fructose diet mouse model. A six-week treatment of CAE (from the fifth week) significantly attenuated the weights of the body, liver, and mesenteric fat without a change in diet intake. CAE also considerably restored the alterations of serum aminotransferases and free fatty acid, fasting blood glucose, serum and hepatic triglyceride, and total cholesterol, as well as platelet and leukocyte counts. Meanwhile, CAE ameliorated hepatic injury and lipid accumulation, as evidenced by histopathological and immunofluorescence observations. Additionally, CAE significantly lowered the elevation of hepatic TNF-α, the TNF-α/IL-10 ratio, fecal endotoxins, and the abundance of Gram-negative bacteria. Hepatic lipogenesis and β-oxidation-related proteins and gene expression, including PPAR-α, SREBP-1, SIRT1, FAS, CTP1, etc., were normalized markedly by CAE. In particular, the AMPK, a central regulator of energy metabolism, was phosphorylated by CAE at an even higher rate than metformin. Overall, CAE exerts anti-hepatic steatosis effects by reducing lipogenesis and enhancing fatty acid oxidation. Consequently, Cynanchum atratum is expected to be a promising candidate for treating chronic metabolic diseases.

Abstract 17036: Cardiomyocyte Krüppel-Like Factor 5 Regulates Ceramide Biosynthesis and Promotes Systolic Dysfunction in Ischemic Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Matthew K Hoffman ◽  
Ioannis Kyriazis ◽  
Dimitra Palioura ◽  
Maria Cimini ◽  
Sudarsan Rajan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
De Novo ◽  
Systolic Dysfunction ◽  
Ischemic Heart ◽  
Acid Oxidation ◽  
Ischemic Heart Failure ◽  
Specific Expression ◽  
Protein Levels

Introduction: Our lab previously showed that cardiomyocyte Krüppel-like factor (KLF)-5 regulates cardiac fatty acid oxidation. Various studies have associated heart failure with altered cardiac fatty acid oxidation and lipotoxicity. Hypothesis: Aberrant regulation of KLF5 contributes to pathophysiology and metabolic perturbations in ischemic heart failure. Methods and Results: Analysis of KLF5 mRNA and protein levels in human ischemic heart failure samples and in rodent models 2- and 4-weeks post-myocardial infarction (MI) showed significantly increased KLF5 expression. To investigate the involvement of KLF5 in the pathophysiology of ischemic heart failure, we treated mice that were subjected to MI with a pharmacological KLF5 inhibitor (ML264). ML264 increased ejection fraction and reduced diastolic volume. Likewise, mice with cardiomyocyte-specific KLF5 deletion (αMHC-KLF5 -/- mice) were protected from ischemic heart failure. Lipidomic analysis by LC-MS/MS showed that αMHC-KLF5 -/- mice after MI had lower myocardial ceramide levels compared with control mice with MI. Accordingly, the expression of cardiac SPTLC1 and SPTLC2, which regulate de novo ceramide biosynthesis, was higher in control mice with MI and lower in αMHC-KLF5 -/- mice with MI. KLF5 overexpression in HL1 cardiomyocytes increased SPTLC1 and SPTLC2 mRNA and protein levels. ChIP-qPCR and luciferase promoter assays showed that KLF5 activates the promoters of these genes via direct binding. To assess the transcriptional effects of KLF5 independent from other changes that occur with MI, we generated a mouse model of inducible (Dox-ON), cardiomyocyte-specific expression of KLF5 (αMHC-rtTA-KLF5). Systolic dysfunction was evident 2-weeks following KLF5 induction. Heart tissue from these mice exhibited increased SPTLC1 and SPTLC2 mRNA and protein levels, and inhibition of SPT using myriocin suppressed myocardial ceramide levels and alleviated systolic dysfunction. Conclusions: KLF5 is induced during the development of ischemic heart failure in humans and mice, and stimulates expression of SPTLC1 and SPTLC2 that promote ceramide biosynthesis. KLF5 inhibition emerges as a novel therapeutic target to protect against ischemic heart failure.

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 Vitamin B12 Induces Hepatic Fatty Infiltration through Altered Fatty Acid Metabolism

2021 ◽  
Vol 55 (3) ◽  
pp. 241-255
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Vitamin B12 ◽  
Fatty Acid Oxidation ◽  
Lipid Droplets ◽  
De Novo ◽  
Quantitative Polymerase Chain Reaction ◽  
Saturated Fatty Acids ◽  
Fatty Infiltration ◽  
Acid Oxidation

Background/Aims: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored. Methods: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay. Results: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control. Conclusion: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12.

scholarly journals Inhibition of Atherosclerosis and Liver Steatosis by Agmatine in Western Diet-Fed apoE-Knockout Mice Is Associated with Decrease in Hepatic De Novo Lipogenesis and Reduction in Plasma Triglyceride/High-Density Lipoprotein Cholesterol Ratio

2021 ◽  
Vol 22 (19) ◽  
pp. 10688
Author(s):  
Anna Wiśniewska ◽  
Aneta Stachowicz ◽  
Katarzyna Kuś ◽  
Magdalena Ulatowska-Białas ◽  
Justyna Totoń-Żurańska ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
De Novo ◽  
Therapeutic Potential ◽  
Liver Steatosis ◽  
Western Diet ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Cholesterol Ratio ◽  
Triglyceride Accumulation

Atherosclerosis and NAFLD are the leading causes of death worldwide. The hallmark of NAFLD is triglyceride accumulation caused by an imbalance between lipogenesis de novo and fatty acid oxidation. Agmatine, an endogenous metabolite of arginine, exerts a protective effect on mitochondria and can modulate fatty acid metabolism. In the present study, we investigate the influence of agmatine on the progression of atherosclerotic lesions and the development of hepatic steatosis in apoE−/− mice fed with a Western high-fat diet, with a particular focus on its effects on the DNL pathway in the liver. We have proved that treatment of agmatine inhibits the progression of atherosclerosis and attenuates hepatic steatosis in apoE−/− mice on a Western diet. Such effects are associated with decreased total macrophage content in atherosclerotic plaque as well as a decrease in the TG levels and the TG/HDL ratio in plasma. Agmatine also reduced TG accumulation in the liver and decreased the expression of hepatic genes and proteins involved in lipogenesis de novo such as SREBP-1c, FASN and SCD1. In conclusion, agmatine may present therapeutic potential for the treatment of atherosclerosis and fatty liver disease. However, an exact understanding of the mechanisms of the advantageous actions of agmatine requires further study.

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