Limits...
Extracts from Aralia elata (Miq) Seem alleviate hepatosteatosis via improving hepatic insulin sensitivity.

Hwang KA, Hwang YJ, Kim GR, Choe JS - BMC Complement Altern Med (2015)

Bottom Line: Treatment with AE extract significantly decreased body weight and the fasting glucose level, alleviated hyperinsulinism and hyperlipidemia, and reduced glucose levels, as determined by OGTT.Additionally, AE extract decreased PI3K and Akt activity.Our results suggest that treatment with AE extract ameliorated NAFLD by inhibiting insulin resistance through activation of the Akt/GLUT4 pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do, 565-851, Republic of Korea. kah366@korea.kr.

ABSTRACT

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease that is strongly associated with obesity and dysregulation of insulin in the liver. However, currently no pharmacological agents have been established for the treatment of NAFLD. In this regard, we sought to evaluate the anti-NAFLD effects of Aralia elata (Miq) Seem (AE) extract and its ability to inhibit hepatic lipid accumulation and modulate cellular signaling in a high fat diet (HFD)-induced obese mouse model.

Methods: A model of hepatic steatosis in the HepG2 cells was induced by oleic acid. Intracellular lipid droplets were detected by Oil-Red-O staining, and the expression of sterol regulatory element-binding protein 1(SREBP-1), Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC) 1 and 2, Peroxisome proliferator activated receptor-α (PPARα), and carnitine palmitoyl transferase 1(CPT-1) was analyzed by real time reverse transcription-Polymerase chain reaction (qRT-PCR). And glucose consumption was measured with commercial kit. Furthermore, Male C57BL/6 J mice were fed with HFD to induce NAFLD. Groups of mice were given plant extracts orally at 100 and 300 mg/kg at daily for 4 weeks. After 3 weeks of AE extract treatment, we performed oral glucose tolerance test (OGTT). Liver tissue was procured for histological examination, Phosphoinositide 3-kinase (PI3K) and Protein kinase B (PKB/Akt) activity.

Results: In the present study, AE extract was shown to reduce hepatic lipid accumulation and significantly downregulate the level of lipogenic genes and upregulate the expression of lipolysis genes in HepG2 cells. And also, AE extract significantly increased the glucose consumption, indicating that AE extract improved insulin resistance. Subsequently, we confirmed the inhibitory activity of AE extract on NAFLD, in vivo. Treatment with AE extract significantly decreased body weight and the fasting glucose level, alleviated hyperinsulinism and hyperlipidemia, and reduced glucose levels, as determined by OGTT. Additionally, AE extract decreased PI3K and Akt activity.

Conclusions: Our results suggest that treatment with AE extract ameliorated NAFLD by inhibiting insulin resistance through activation of the Akt/GLUT4 pathway.

No MeSH data available.


Related in: MedlinePlus

Effects of Aralia elata (Miq) Seem (AE) on lipid metabolism-associated genes in HepG2 cells. HepG2 cells were treated with 100 μg/mL AE and OA. After treatment for 24 h, RNA was isolated and reverse transcribed for RTPCR analysis using the primers described in materials and methods. Results are the mean ± SEM. *p < 0.05 compared with the OA group. DMEM, control group; OA, oleic acid-treated group; AE, OA+ Aralia elata (Miq) Seem-treated group; RV, OA+ resveratrol-treated group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4595215&req=5

Fig3: Effects of Aralia elata (Miq) Seem (AE) on lipid metabolism-associated genes in HepG2 cells. HepG2 cells were treated with 100 μg/mL AE and OA. After treatment for 24 h, RNA was isolated and reverse transcribed for RTPCR analysis using the primers described in materials and methods. Results are the mean ± SEM. *p < 0.05 compared with the OA group. DMEM, control group; OA, oleic acid-treated group; AE, OA+ Aralia elata (Miq) Seem-treated group; RV, OA+ resveratrol-treated group

Mentions: Relative mRNA expression levels of lipid metabolism and insulin signaling markers were determined using quantitative PCR. As shown in Fig. 3, mRNA expression levels of hepatic lipogenesis genes such as sterol regulatory element-binding protein 1(SREBP-1), fatty acid synthase(FAS), and acetyl-CoA carboxylase (ACC) 1 increased in the OA-treated cells. AE-treated HepG2 cells showed an inhibition of the mRNA expression levels. Furthermore, mRNA expression levels of peroxisome proliferator activated receptor-α (PPARα), carnitine palmitoyl transferase 1(CPT-1), and ACC2 genes, which are regulators of lipolysis, significantly increased when HepG2 cells were treated with AE. In addition, to demonstrate the effect of AE extract in regulating insulin signaling transduction, we analyzed molecular expression in insulin signaling pathway in HepG2 cells. With AE treatment, the Insulin receptor substrate (IRS) -1/2 mRNA expression significantly increased compared to the OA group. Akt, glucose transport (GLUT2) are the downstream molecules of IRS in insulin pathway. The Akt and GLUT2 expression in OA-treated group was decreased, while AE-treated group increased the hepatic Akt and GLUT2 expression (Additional file 1: Figure S1). These data together suggest strongly an improvement in hepatic lipid metabolism and insulin sensitivity with AE treatment.Fig. 3


Extracts from Aralia elata (Miq) Seem alleviate hepatosteatosis via improving hepatic insulin sensitivity.

Hwang KA, Hwang YJ, Kim GR, Choe JS - BMC Complement Altern Med (2015)

Effects of Aralia elata (Miq) Seem (AE) on lipid metabolism-associated genes in HepG2 cells. HepG2 cells were treated with 100 μg/mL AE and OA. After treatment for 24 h, RNA was isolated and reverse transcribed for RTPCR analysis using the primers described in materials and methods. Results are the mean ± SEM. *p < 0.05 compared with the OA group. DMEM, control group; OA, oleic acid-treated group; AE, OA+ Aralia elata (Miq) Seem-treated group; RV, OA+ resveratrol-treated group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4595215&req=5

Fig3: Effects of Aralia elata (Miq) Seem (AE) on lipid metabolism-associated genes in HepG2 cells. HepG2 cells were treated with 100 μg/mL AE and OA. After treatment for 24 h, RNA was isolated and reverse transcribed for RTPCR analysis using the primers described in materials and methods. Results are the mean ± SEM. *p < 0.05 compared with the OA group. DMEM, control group; OA, oleic acid-treated group; AE, OA+ Aralia elata (Miq) Seem-treated group; RV, OA+ resveratrol-treated group
Mentions: Relative mRNA expression levels of lipid metabolism and insulin signaling markers were determined using quantitative PCR. As shown in Fig. 3, mRNA expression levels of hepatic lipogenesis genes such as sterol regulatory element-binding protein 1(SREBP-1), fatty acid synthase(FAS), and acetyl-CoA carboxylase (ACC) 1 increased in the OA-treated cells. AE-treated HepG2 cells showed an inhibition of the mRNA expression levels. Furthermore, mRNA expression levels of peroxisome proliferator activated receptor-α (PPARα), carnitine palmitoyl transferase 1(CPT-1), and ACC2 genes, which are regulators of lipolysis, significantly increased when HepG2 cells were treated with AE. In addition, to demonstrate the effect of AE extract in regulating insulin signaling transduction, we analyzed molecular expression in insulin signaling pathway in HepG2 cells. With AE treatment, the Insulin receptor substrate (IRS) -1/2 mRNA expression significantly increased compared to the OA group. Akt, glucose transport (GLUT2) are the downstream molecules of IRS in insulin pathway. The Akt and GLUT2 expression in OA-treated group was decreased, while AE-treated group increased the hepatic Akt and GLUT2 expression (Additional file 1: Figure S1). These data together suggest strongly an improvement in hepatic lipid metabolism and insulin sensitivity with AE treatment.Fig. 3

Bottom Line: Treatment with AE extract significantly decreased body weight and the fasting glucose level, alleviated hyperinsulinism and hyperlipidemia, and reduced glucose levels, as determined by OGTT.Additionally, AE extract decreased PI3K and Akt activity.Our results suggest that treatment with AE extract ameliorated NAFLD by inhibiting insulin resistance through activation of the Akt/GLUT4 pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do, 565-851, Republic of Korea. kah366@korea.kr.

ABSTRACT

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease that is strongly associated with obesity and dysregulation of insulin in the liver. However, currently no pharmacological agents have been established for the treatment of NAFLD. In this regard, we sought to evaluate the anti-NAFLD effects of Aralia elata (Miq) Seem (AE) extract and its ability to inhibit hepatic lipid accumulation and modulate cellular signaling in a high fat diet (HFD)-induced obese mouse model.

Methods: A model of hepatic steatosis in the HepG2 cells was induced by oleic acid. Intracellular lipid droplets were detected by Oil-Red-O staining, and the expression of sterol regulatory element-binding protein 1(SREBP-1), Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC) 1 and 2, Peroxisome proliferator activated receptor-α (PPARα), and carnitine palmitoyl transferase 1(CPT-1) was analyzed by real time reverse transcription-Polymerase chain reaction (qRT-PCR). And glucose consumption was measured with commercial kit. Furthermore, Male C57BL/6 J mice were fed with HFD to induce NAFLD. Groups of mice were given plant extracts orally at 100 and 300 mg/kg at daily for 4 weeks. After 3 weeks of AE extract treatment, we performed oral glucose tolerance test (OGTT). Liver tissue was procured for histological examination, Phosphoinositide 3-kinase (PI3K) and Protein kinase B (PKB/Akt) activity.

Results: In the present study, AE extract was shown to reduce hepatic lipid accumulation and significantly downregulate the level of lipogenic genes and upregulate the expression of lipolysis genes in HepG2 cells. And also, AE extract significantly increased the glucose consumption, indicating that AE extract improved insulin resistance. Subsequently, we confirmed the inhibitory activity of AE extract on NAFLD, in vivo. Treatment with AE extract significantly decreased body weight and the fasting glucose level, alleviated hyperinsulinism and hyperlipidemia, and reduced glucose levels, as determined by OGTT. Additionally, AE extract decreased PI3K and Akt activity.

Conclusions: Our results suggest that treatment with AE extract ameliorated NAFLD by inhibiting insulin resistance through activation of the Akt/GLUT4 pathway.

No MeSH data available.


Related in: MedlinePlus