scholarly journals AGL9: A Novel Hepatoprotective Peptide from the Larvae of Edible Insects Alleviates Obesity-Induced Hepatic Inflammation by Regulating AMPK/Nrf2 Signaling

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1973
Author(s):  
Meiqi Fan ◽  
Young-Jin Choi ◽  
Yujiao Tang ◽  
Ji Hye Kim ◽  
Byung-gyu Kim ◽  
...  
Keyword(s):  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Transcript Level ◽  
Monocyte Chemoattractant Protein 1 ◽  
Nonalcoholic Fatty Liver ◽  
Nuclear Respiratory Factor ◽  
Proinflammatory Mediators ◽  
Factor Α

In this study, we investigated the anti-obesity properties of the novel peptide Ala-Gly-Leu-Gln-Phe-Pro-Val-Gly-Arg (AGL9), isolated from the enzymatic hydrolysate of Allomyrina dichotoma larvae. To investigate the preventive effects of AGL9 against hepatic steatosis and its possible mechanisms of action, we established an nonalcoholic fatty liver disease (NAFLD) model by feeding C57BL/6 mice a high-fat diet. NAFLD mice were administered 100 mg/kg AGL9 and 60 mg/kg orlistat via gavage (10 mL/kg) for 5 weeks, followed by the collection of blood and liver tissues. We found that AGL9 normalized the levels of serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, high-density lipoprotein, very low-density lipoprotein (LDL)/LDL, adiponectin, and leptin in these mice. Additionally, AGL9 activated the protein-level expression of 5’ AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation and the transcript-level expression of sterol regulatory element-binding protein-1c, fatty acid synthase, superoxide dismutase, glutathione peroxidase, glucocorticoid receptor, nuclear respiratory factor 2, tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 in hepatocytes. These results showed that AGL9 exhibited hepatoprotective effects by attenuating lipid deposition, oxidative stress, and inflammation via inhibition of AMPK/Nrf2 signaling, thereby reducing the production of hepatic proinflammatory mediators and indicating AGL9 as a potential therapeutic strategy for NAFLD.

scholarly journals Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

2012 ◽  
Vol 1 (3) ◽  
pp. 129-136
Author(s):  
Jun Cheng ◽  
Min Li ◽  
Ping Gao ◽  
Jin-ling Dong ◽  
Qi Wang
Keyword(s):  
Hepatitis C ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Low Density Lipoprotein ◽  
Liver Steatosis ◽  
Lipid Synthesis ◽  
Density Lipoprotein ◽  
Hcv Infection ◽  
Low Density ◽  
Lipid Uptake

Abstract Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC). Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV) infection. Level of low density lipoprotein receptor (LDL-R) and activity of peroxisome proliferator-activated receptor (PPAR) α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP), and formation of very low density lipoprotein (VLDL) have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP)-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN), HMG CoA reductase (HMGCR), liver X receptor (LXR), acetyl-CoA carboxylase 1 (ACC1), hepatic CB (1) receptors, retinoid X receptor (RXR) α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

scholarly journals SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

2020 ◽  
Vol 21 (12) ◽  
pp. 4534
Author(s):  
Da Eun Kim ◽  
Bo Yoon Chang ◽  
Byeong Min Jeon ◽  
Jong In Baek ◽  
Sun Chang Kim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Density Lipoprotein ◽  
Nonalcoholic Fatty Liver

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

2018 ◽  
Vol 74 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Joanna J. Samulak ◽  
Angelika K. Sawicka ◽  
Dace Hartmane ◽  
Solveiga Grinberga ◽  
Osvalds Pugovics ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Adhesion Molecule ◽  
Serum Proteins ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Intercellular Adhesion Molecule ◽  
Carnitine Supplementation ◽  
Intercellular Adhesion Molecule 1 ◽  
Factor Α

Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that ­although oral L-carnitine supplementation significantly ­increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

Clofibrate causes an upregulation of PPAR-α target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs

2007 ◽  
Vol 293 (1) ◽  
pp. R70-R77 ◽  
Author(s):  
Sebastian Luci ◽  
Beatrice Giemsa ◽  
Holger Kluge ◽  
Klaus Eder
Keyword(s):  
Adipose Tissue ◽  
Target Genes ◽  
Regulatory Element ◽  
Control Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Expression

This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-α and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-α target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs ( P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes ( Insig) -1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-α in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-α activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs.

Abstract P080: Fructose Acutely Increases Size of Very Low Density Lipoprotein In Adolescents With Hepatic Steatosis

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Mirian Vos ◽  
Ran Jin ◽  
Jean Welsh ◽  
Ngoc-Anh Le
Keyword(s):  
Hepatic Steatosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Complications ◽  
Plasma Lipoproteins ◽  
Healthy Children ◽  
Mri Imaging ◽  
Nonalcoholic Fatty Liver ◽  
Obese Adolescents ◽  
Acute Response

Introduction: Cardiovascular complications are a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). Fructose has been reported to be associated with dyslipidemia and increased cardiovascular risk in adults but its impact on adolescents with NAFLD is not well understood. We previously demonstrated that fructose disproportionately increased postprandial hypertriglyceridemia in pediatric NAFLD as compared to healthy children. However, the mechanism remains unclear. Hypothesis: We hypothesized that fructose would contribute to hypertriglyceridemia in pediatric NAFLD by increasing the size of VLDL particles. Methods: We examined the acute response to a single dose of fructose beverage in 50 Hispanic-American obese adolescents with varying degrees of hepatic steatosis. Those with hepatic fat >5% on MRI imaging were designated as presumed NAFLD. Subjects consumed a 12oz drink containing 33g of fructose and plasma samples were collected at baseline and 30, 60, and 90 minutes afterwards. Plasma lipoproteins were measured using NMR (Liposcience, Raleigh, NC). Results: In response to acute fructose load, subjects without NAFLD increased the total number of TG rich lipoprotein particles (p = 0.047). However, this increase was not observed in subjects with NAFLD; instead, they increased the subpopulation of large VLDL particles (p = 0.008) and the mean size of VLDL particles (p = 0.004) (Figure 1). In line with this finding, TG-to-apoB ratio significantly increased in subjects with NAFLD (2.25 ± 0.26 to 2.37 ± 0.25, p = 0.031) but not in non-NAFLD. Conclusions: These findings demonstrate that adolescents with NAFLD have more atherogenic, large VLDL in response to fructose compared to obese adolescents without NAFLD. Dietary fructose restriction may be a critical component in the treatment of NAFLD associated cardiovascular disease and should be tested further.

scholarly journals Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-catenin Expression

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1460 ◽  
Author(s):  
Im ◽  
Kim ◽  
Chau ◽  
Um
Keyword(s):  
Fatty Acid Synthase ◽  
Glycogen Synthase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Negative Regulator ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Levels ◽  
Density Lipoprotein Receptor ◽  
Prevalence Of Obesity

Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity, remains unclear. Here, we show that carbamazepine increased the expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and fatty acid synthase (FASN) in 3T3-L1 cells. Notably, carbamazepine inhibited the expression levels of β-catenin, a negative regulator of adipogenesis, leading to enhanced adipogenesis. Conversely, β-catenin overexpression abolished the effect of carbamazepine on adipogenic gene expression. However, depletion of β-catenin further enhanced PPARγ expression. In addition, carbamazepine reduced β-catenin expression by lowering the levels of phospho-low density lipoprotein receptor-related protein 6 (p-LRP6) and phospho-glycogen synthase kinase 3β (p-GSK3β) in Wnt/β-catenin signaling. Moreover, carbamazepine reduced Wnt mRNA expression and decreased the promoter activities of TCF, the target of β-catenin during adipogenesis. These results suggest that carbamazepine enhances adipogenesis by suppressing Wnt/β-catenin expression, indicating its potential effects on obesity-related metabolism.

scholarly journals Oxidized LDL Modify the Human Adipocyte Phenotype to an Insulin Resistant, Proinflamatory and Proapoptotic Profile

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 534 ◽  
Author(s):  
Concepción Santiago-Fernández ◽  
Flores Martin-Reyes ◽  
Mónica Tome ◽  
Luis Ocaña-Wilhelmi ◽  
Jose Rivas-Becerra ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Morbidly Obese ◽  
Insulin Resistant ◽  
Tnf Α ◽  
Obese Subjects ◽  
Factor Α ◽  
Visceral Adipose

Little information exists in humans on the regulation that oxidized low-density lipoprotein (oxLDL) exerts on adipocyte metabolism, which is associated with obesity and type 2 diabetes. The aim was to analyze the oxLDL effects on adipocytokine secretion and scavenger receptors (SRs) and cell death markers in human visceral adipocytes. Human differentiated adipocytes from visceral adipose tissue from non-obese and morbidly obese subjects were incubated with increasing oxLDL concentrations. mRNA expression of SRs, markers of apoptosis and autophagy, secretion of adipocytokines, and glucose uptake were analyzed. In non-obese and in morbidly obese subjects, oxLDL produced a decrease in insulin-induced glucose uptake, a significant dose-dependent increase in tumor necrosis factor-α (TNF-α), IL-6, and adiponectin secretion, and a decrease in leptin secretion. OxLDL produced a significant increase of Lox-1 and a decrease in Cxcl16 and Cl-p1 expression. The expression of Bnip3 (marker of apoptosis, necrosis and autophagy) was significantly increased and Bcl2 (antiapoptotic marker) was decreased. OxLDL could sensitize adipocytes to a lower insulin-induced glucose uptake, a more proinflammatory phenotype, and could modify the gene expression involved in apoptosis, autophagy, necrosis, and mitophagy. OxLDL can upregulate Lox-1, and this could lead to a possible amplification of proinflammatory and proapoptotic effects of oxLDL.

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