scholarly journals Four sesquiterpene glycosides from loquat (Eriobotrya japonica) leaf ameliorates palmitic acid-induced insulin resistance and lipid accumulation in HepG2 Cells via AMPK signaling pathway

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10413
Author(s):  
Jiawei Li ◽  
Xiaoqin Ding ◽  
Tunyu Jian ◽  
Han Lü ◽  
Lei Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Palmitic Acid ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Eriobotrya Japonica ◽  
Expression Levels ◽  
Ampk Signaling ◽  
Insulin Resistant ◽  
Compound C

Insulin resistance (IR), caused by impaired insulin signal and decreased insulin sensitivity, is generally responsible for the pathophysiology of type 2 diabetes mellitus (T2DM). Sesquiterpene glycosides (SGs), the exclusive natural products from loquat leaf, have been regarded as potential lead compounds owing to their high efficacy in hypoglycemia and hypolipidemia. Here, we evaluated the beneficial effects of four single SGs isolated from loquat leaf, including SG1, SG2, SG3 and one novel compound SG4 against palmitic acid-induced insulin resistance in HepG2 cells. SG1, SG3 and SG4 could significantly enhance glucose uptake of insulin-resistant HepG2 cells at non-cytotoxic concentration. Meanwhile, Oil Red O staining showed the decrease of both total cholesterol and triglyceride content, suggesting the amelioration of lipid accumulation by SGs in insulin-resistant HepG2 cells. Further investigations found that the expression levels of phosphorylated AMPK, ACC, IRS-1, and Akt were significantly up-regulated after SGs treatment, on the contrary, the expression levels of SREBP-1 and FAS were significantly down-regulated. Notably, AMPK inhibitor Compound C (CC) blocked the regulative effects, while AMPK activator AICAR mimicked the effects of SGs in PA-treated insulin-resistant HepG2 cells. In conclusion, SGs (SG4>SG1≈SG3>SG2) improved lipid accumulation in insulin-resistant HepG2 cells through the AMPK signaling pathway.

scholarly journals RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Mei Han ◽  
Lianghui You ◽  
Yanting Wu ◽  
Nan Gu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Palmitic Acid ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Metabolic Diseases ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
C2c12 Myotubes ◽  
Insulin Resistant

Abstract Insulin resistance (IR) has been considered as the common pathological basis and developmental driving force for most metabolic diseases. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators in modulation of glucose and lipid metabolism. However, the comprehensive profile of lncRNAs in skeletal muscle cells under the insulin resistant status and the possible biological effects of them were not fully studied. In this research, using C2C12 myotubes as cell models in vitro, deep RNA-sequencing was performed to profile lncRNAs and mRNAs between palmitic acid-induced IR C2C12 myotubes and control ones. The results revealed that a total of 144 lncRNAs including 70 up-regulated and 74 down-regulated (|fold change| > 2, q < 0.05) were significantly differentially expressed in palmitic acid-induced insulin resistant cells. In addition, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases revealed that the target genes of the differentially expressed lncRNAs were significantly enriched in fatty acid oxidation, lipid oxidation, PPAR signaling pathway, and insulin signaling pathway. Moreover, Via qPCR, most of selected lncRNAs in myotubes and db/db mice skeletal muscle showed the consistent expression trends with RNA-sequencing. Co-expression analysis also explicated the key lncRNA–mRNA interactions and pointed out a potential regulatory network of candidate lncRNA ENSMUST00000160839. In conclusion, the present study extended the skeletal muscle lncRNA database and provided novel potential regulators for future genetic and molecular studies on insulin resistance, which is helpful for prevention and treatment of the related metabolic diseases.

scholarly journals Theaflavins Improve Insulin Sensitivity through Regulating Mitochondrial Biosynthesis in Palmitic Acid-Induced HepG2 Cells

2018 ◽  
Author(s):  
Tuantuan Tong ◽  
Ning Ren ◽  
Jiafan Wu ◽  
Na Guo ◽  
Xiaobo Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Palmitic Acid ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Hepatic Insulin Resistance ◽  
Insulin Resistant ◽  
Mitochondrial Dna Copy Number ◽  
Increase Glucose Uptake

Theaflavins, the characteristic and bioactive polyphenols in black tea, possess the potential improvement effects on insulin resistance-associated metabolic abnormalities including obesity and type 2 diebetes. However, the molecular mechanisms of theaflavins improving insulin sensitivity are still not clear. In this study, we investigated the protective effects and mechanisms of theaflavins on palmitic acid-induced insulin resistance in HepG2 cells. Theaflavins could significantly increase glucose uptake of insulin-resistant cells at noncytotoxic doses. This activity was mediated by upregulating the glucose transporter 4 protein expression, increasing the phosphorylation of IRS-1 at Ser307, and reduced the phosphor-Akt (Ser473) level. Moreover, theaflavins were found to enhance mitochondrial DNA copy number through down-regulate the PGC-1β mRNA level and up-regulate PRC mRNA expression in insulin-resistant HepG2 cells. These results indicated that theaflavins could improve free fatty acid-induced hepatic insulin resistance by promoting mitochondrial biogenesis, and were promising functional food and medicines for insulin resistance-related disorders.

Chalcones suppress fatty acid-induced lipid accumulation through a LKB1/AMPK signaling pathway in HepG2 cells

2014 ◽  
Vol 5 (6) ◽  
pp. 1134-1141 ◽  
Author(s):  
Tianshun Zhang ◽  
Norio Yamamoto ◽  
Hitoshi Ashida
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Ampk Signaling

Excessive lipid accumulation in the liver has been proposed to cause hyperlipidemia, diabetes and fatty liver disease.

C-Phycocyanin inhibits hepatic gluconeogenesis and increases glycogen synthesis via activating Akt and AMPK in insulin resistance hepatocytes

2018 ◽  
Vol 9 (5) ◽  
pp. 2829-2839 ◽  
Author(s):  
Zhiheng Ren ◽  
Zhifei Xie ◽  
Danni Cao ◽  
Mufeng Gong ◽  
Lei Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Glycogen Synthesis ◽  
Hepatic Gluconeogenesis ◽  
Ampk Signaling ◽  
Insulin Resistant ◽  
Glucose Homoeostasis

The mechanism of C-PC in improving glucose homoeostasis is to activate the IRS/PI3 K/Akt and SIRT1/LKB1/AMPK signaling pathway in insulin resistant hepatocytes.

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