scholarly journals Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4015
Author(s):  
Hong Qin ◽  
Ziyu Song ◽  
Horia Shaukat ◽  
Wenya Zheng
Keyword(s):  
Estrogen Receptor ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Estrogen Receptor Β ◽  
Peroxisome Proliferator ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Genistein (GEN) has been shown to significantly inhibit hepatic triglyceride accretion triggered by estrogen deficiency. The main purpose of this in vitro study was to investigate the function and molecular mechanism of estrogen receptor β (ERβ) in regulating hepatic lipid metabolism induced by GEN. Different doses of GEN or GEN with an ERβ antagonist were treated with HepG2 cells. Results showed that 25 μM GEN significantly diminished triglyceride levels. Meanwhile, GEN downregulated the levels of genes and proteins involved in lipogenesis, such as sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and stearoyl-coenzyme A desaturase 1 (SCD1), and upregulated the gene and protein levels of the regulation factors responsible for fatty acid β-oxidation, such as carnitine palmitoyltransferase 1α (CPT-1α) and peroxisome proliferator-activated receptor α (PPARα). Furthermore, 25 μM GEN reduced the levels of phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Moreover, most of these effects from GEN were reverted by pretreatment with the antagonist of ERβ. In conclusion, GEN improved hepatic lipid metabolism by activating ERβ and further modulation of Akt/mTOR signals. The results provide novel aspects of the regulatory mechanism of ERβ on hepatic lipid metabolism and might help to profoundly understand the functions of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women.

scholarly journals Maternal high-fat diet consumption modulates hepatic lipid metabolism and microRNA-122 (miR-122) and microRNA-370 (miR-370) expression in offspring

2014 ◽  
Vol 111 (12) ◽  
pp. 2112-2122 ◽  
Author(s):  
R. O. Benatti ◽  
A. M. Melo ◽  
F. O. Borges ◽  
L. M. Ignacio-Souza ◽  
L. A. P. Simino ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
High Fat ◽  
Hepatic Lipid Metabolism ◽  
Expression Levels ◽  
Hepatic Lipid ◽  
Pregnancy And Lactation ◽  
Maternal Consumption

Maternal consumption of a high-fat diet (HFD) during pregnancy and lactation is closely related to hepatic lipid accumulation, insulin resistance and increased serum cytokine levels in offspring and into their adulthood. MicroRNA (miRNA) have been implicated in cholesterol biosynthesis and fatty acid metabolism. We evaluated the modulation of hepatic fatty acid synthesis (de novo), β-oxidation pathways, and miRNA-122 (miR-122) and miRNA-370 (miR-370) expression in recently weaned offspring (day 28) of mouse dams fed a HFD (HFD-O) or a standard chow (SC-O) during pregnancy and lactation. Compared with SC-O mice, HFD-O mice weighed more, had a larger adipose tissue mass and were more intolerant to glucose and insulin (P< 0·05). HFD-O mice also presented more levels of serum cholesterol, TAG, NEFA and hepatic IκB kinase and c-Jun N-terminal kinase phosphorylation compared with SC-O mice (P< 0·05). Protein levels of fatty acid synthase, acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase were similar in HFD-O and SC-O mice, whereas expression levels of SCD1 mRNA and protein were more abundant in HFD-O mice than in SC-O mice (P< 0·05). Interestingly, mRNA expression levels of the β-oxidation-related genes ACADVL and CPT1 were decreased in HFD-O mice (P< 0·05). Furthermore, the expression of miR-122 was reduced but that of miR-370 was increased in HFD-O mice compared with that in SC-O mice (P< 0·05). Changes in hepatic lipid metabolism were accompanied by increased mRNA content of AGPAT1 and TAG deposition in HFD-O mice (P< 0·05). Taken together, the present results strongly suggest that maternal consumption of a HFD affects the early lipid metabolism of offspring by modulating the expression of hepatic β-oxidation-related genes and miRNA that can contribute to metabolic disturbances in adult life.

Dietary threonine supplementation improves hepatic lipid metabolism of Pekin ducks

2019 ◽  
Vol 59 (4) ◽  
pp. 673 ◽  
Author(s):  
Y. Jiang ◽  
X. D. Liao ◽  
M. Xie ◽  
J. Tang ◽  
S. Y. Qiao ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Initiation Factor ◽  
Pekin Duck ◽  
Hepatic Lipid Metabolism ◽  
Fatty Acid Binding ◽  
Hepatic Lipid ◽  
Pekin Ducks

The present study was conducted to evaluate the regulatory role of threonine (Thr) on hepatic lipid metabolism by determining the effects of dietary Thr concentration on lipid deposition and on genes related to lipid expression in the liver of Pekin duck. In total, 240 1-day-old ducklings were randomly allocated according to the average bodyweight to one of five dietary treatments with six replicate cages of eight birds per cage for each treatment. Birds were fed diets with 0.52%, 0.59%, 0.66%, 0.73% and 0.80% Thr (as-fed basis) from 1 to 21 days of age respectively. The results showed that dietary Thr supplementation increased average daily gain (P &lt; 0.0001), average daily feed intake (P &lt; 0.0001) and abdominal fat percentage (P &lt; 0.04), while it decreased feed to gain ratio (P &lt; 0.0001), the hepatic contents of total lipid (P &lt; 0.003) and triglycerides (P &lt; 0.003) of Pekin ducks. However, dietary Thr supplementation had no influence (P &gt; 0.05) on the concentration of hepatic cholesterol, and plasma amino acids and biochemical parameters of Pekin ducks. Moreover, Thr-unsupplemented control diet upregulated (P &lt; 0.05) hepatic gene expression related to lipid uptake (fatty acid-binding protein, apolipoprotein A4, lipoprotein lipase), fatty acid synthesis (sterol regulatory element-binding protein 1c, malic enzyme), fatty acid β-oxidation (peroxisome proliferator-activated receptor α, fatty acyl– coenzyme A (CoA) oxidase), ketogenesis (hydroxymethylglutaryl–CoA synthase 1, and acetyl–CoA synthetase1), responsive genes to amino acid deficiency (general control non-derepressible 2 (GCN2), GCN1, eukaryotic initiation factor 2α, impact RWD domain protein (IMPACT)), and triglyceride transport (apolipoprotein B) of Pekin ducks. In addition, dietary Thr deficiency had no effect on the expression of stearoyl CoA desaturase, fatty acid synthase, and ATP–citrate lyase in the liver of Pekin ducks. It is suggested that dietary Thr supplementation improved hepatic lipid metabolism of Pekin ducks by regulating lipid synthesis, transport and oxidation.

scholarly journals Flavonones from Penthorum chinense Ameliorate Hepatic Steatosis by Activating the SIRT1/AMPK Pathway in HepG2 Cells

2018 ◽  
Vol 19 (9) ◽  
pp. 2555 ◽  
Author(s):  
Wei-Wei Guo ◽  
Xing Wang ◽  
Xiao-Qing Chen ◽  
Yin-Ying Ba ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ampk Pathway ◽  
Penthorum Chinense

Pinocembrin-7-O-β-d-glucoside (PCBG), pinocembrin (PCB), and 5-methoxy-pinocembrin-7-O-β-d-glucoside (MPG) are three flavonones isolated from Penthorum chinense Pursh (P. chinense). The effects of the three flavonones on hepatic steatosis and their molecular mechanisms in HepG2 cells were investigated in this study for the first time. A model of hepatic steatosis in HepG2 cells was induced by free fatty acid (FFA), and co-treated with the three flavonones as mentioned. Intracellular lipid droplets were detected by Oil Red O staining. PCB, PCBG, and MPG suppressed oxidative stress by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were ameliorated. Moreover, these flavonones enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of silent mating type information regulation 2 homolog 1 (SIRT1) and peroxisome proliferator-activated receptor α (PPARα), and reduced the expression of sterol regulatory element binding protein-1c (SREBP1c) and the downstream targets fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase 1 (SCD1). Molecular docking was used to predict the interaction and combination patterns between the three flavonones and the enzymes above. The results revealed that the SIRT1/AMPK pathway is involved in the functions of the three flavonones, and the most effective flavonone against hepatic steatosis might be PCBG, followed by MPG and PCB. Therefore, the three flavonones from P. chinense were found to exert preventive effects against hepatic steatosis by regulating the SIRT1/AMPK pathway.

scholarly journals Impact of Dietary Crude Protein Level on Hepatic Lipid Metabolism in Weaned Female Piglets

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1829
Author(s):  
Ning Liu ◽  
Yun Ji ◽  
Ying Yang ◽  
Hai Jia ◽  
Xuemeng Si ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Crude Protein ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Mrna Level ◽  
Building Blocks ◽  
Peroxisome Proliferator ◽  
Hepatic Lipid Metabolism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Lipid

Amino acids serve not only as building blocks for proteins, but also as substrates for the synthesis of low-molecular-weight substances involved in hepatic lipid metabolism. In the present study, eighteen weaned female piglets at 35 days of age were fed a corn- and soybean meal-based diet containing 20%, 17%, or 14% crude protein (CP), respectively. We found that 17% or 20% CP administration reduced the triglyceride and cholesterol concentrations, while enhanced high-density lipoprotein cholesterol (HDL-C) concentration in serum. Western blot analysis showed that piglets in the 20% CP group had higher protein abundance of hormone-sensitive triglyceride lipase (HSL) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), as compared with other groups. Moreover, the mRNA expression of sterol regulatory element binding transcription factor 1 (SREBPF1), fatty acid synthase (FASN), and stearoyl-CoA desaturase (SCD) were lower in the 17% or 20% CP group, compared with those of the piglets administered with 14% CP. Of note, the mRNA level of acetyl-CoA carboxylase alpha (ACACα) was lower in the 17% CP group, compared with other groups. Additionally, the mRNA level of lipoprotein lipase (LPL), peroxisome proliferator-activated receptor alpha α (PPARα), glucose-6-phosphatase catalytic subunit (G6PC), and phosphoenolpyruvate carboxykinase 1 (PKC1) in the liver of piglets in the 20% CP group were higher than those of the 14% CP group. Collectively, our results demonstrated that dietary CP could regulate hepatic lipid metabolism through altering hepatic lipid lipogenesis, lipolysis, oxidation, and gluconeogenesis.

scholarly journals Supplementing conjugated linoleic acid (CLA) in breeder hens diet increased CLA incorporation in liver and alters hepatic lipid metabolism in chick offspring

2021 ◽  
pp. 1-41
Author(s):  
Chun-Yan Fu ◽  
Yan Zhang ◽  
Wen-Bin Wang ◽  
Xiang-Fa Wei ◽  
Pei-Pei Yan ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Fatty Acid Synthase ◽  
Serum Triglyceride ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Breeder Hens ◽  
Expression Of Genes

Abstract This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (CT) or 0.5% CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 days. CLA treatment had no significant influence on development, egg quality, and fertility of breeder hens, but darkened the egg yolks in shade and increased yolk sac mass compared to CT group. Addition of CLA resulted in increased body mass and liver mass, and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum triglyceride (TG) and cholesterol (TC) levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in liver of chick offspring, accompanied by the decreased hepatic TG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased of carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC, and sterol regulatory element-binding protein-1c), and induced the expression of genes related to β-oxidative (CPT1, AMP-activated protein kinase, and peroxisome proliferator-activated receptor α) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased incorporation of CLA in liver of chick offspring, which further regulate hepatic lipid metabolism.

Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism

2020 ◽  
Author(s):  
Manoharan Balachandiran ◽  
Zachariah Bobby ◽  
Gowri Dorairajan ◽  
Sajini Elizabeth Jacob ◽  
Victorraj Gladwin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fetal Growth ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Acid Oxidation ◽  
Placental Proteins

Abstract Introduction Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. Materials and Methods Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. Results Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. Conclusion Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

Acute modulation of rat hepatic lipid metabolism by sulphur-substituted fatty acid analogues

1995 ◽  
Vol 49 (7) ◽  
pp. 1013-1022 ◽  
Author(s):  
Daniel K. Asiedu ◽  
Abraham Demoz ◽  
Jon Skorve ◽  
Hans J. Grav ◽  
Rolf K. Berge
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid
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