Isoliquiritigenin impairs insulin signaling and adipocyte differentiation through the inhibition of protein-tyrosine phosphatase 1B oxidation in 3T3-L1 preadipocytes

Park, Sun-Ji; Choe, Young-Geun; Kim, Jung‐Hak; Chang, Kyu‐Tae; Lee, Hyun‐Shik; Lee, Dong‐Seok

doi:10.1016/j.fct.2016.04.017

Cited by 18 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the adipogenic gene levels were significantly reduced by the antioxidant Nac ( Fig 3 ). These results corroborated those of our previous study [ 24 ]. Therefore, insulin-induced adipogenic-related genes mediate ROS levels in differentiated 3T3-L1 cells.…”

Section: Discussionsupporting

confidence: 94%

“…Expression levels of mitochondrial fusion related proteins, such as OPA1, Mfn1, and Mfn2, gradually increased, as did that of the mitochondrial fission related protein, Drp1, and levels of phosphorylated serine 616 Drp1 also gradually increased during adipocyte differentiation ( Fig 1B ). According to our previous study, insulin treatment elevated expression of antioxidant enzymes in mature adipocytes [ 24 ]. We confirmed the altered expression of antioxidant enzyme levels during adipocyte differentiation.…”

Section: Resultsmentioning

confidence: 99%

“…Studies in humans have revealed that adipose tissue from obese patients is associated with increased systemic oxidative stress, which might indicate a target for new therapies for obesity-related metabolic syndrome [ 50 ]. Our previous study also suggests that antioxidant materials could potentially be used to prevent obesity [ 24 ]. Accordingly, we investigated the levels of antioxidants such as Prxs and SOD.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Insulin-stimulated lipid accumulation is inhibited by ROS-scavenging chemicals, but not by the Drp1 inhibitor Mdivi-1

et al. 2017

Self Cite

View full text Add to dashboard Cite

Adipocyte differentiation is regulated by intracellular reactive oxygen species (ROS) generation and mitochondrial fission and fusion processes. However, the correlation between intracellular ROS generation and mitochondrial remodeling during adipocyte differentiation is still unknown. Here, we investigated the effect on adipocyte differentiation of 3T3-L1 cells of intracellular ROS inhibition using N-acetyl cysteine (Nac) and Mito-TEMPO and of mitochondrial fission inhibition using Mdivi-1. Differentiated 3T3-L1 adipocytes displayed an increase in mitochondrial fission, ROS generation, and the expression of adipogenic and mitochondrial dynamics-related proteins. ROS scavenger (Nac or Mito-TEMPO) treatment inhibited ROS production, lipid accumulation, the expression of adipogenic and mitochondrial dynamics-related proteins, and mitochondrial fission during adipogenesis of 3T3-L1 cells. On the other hand, treatment with the mitochondrial fission inhibitor Mdivi-1 inhibited mitochondrial fission but did not inhibit ROS production, lipid accumulation, or the expression of adipogenic and mitochondrial dynamics-related proteins, with the exception of phosphorylated Drp1 (Ser616), in differentiated 3T3-L1 adipocytes. The inhibition of mitochondrial fission did not affect adipocyte differentiation, while intracellular ROS production decreased in parallel with inhibition of adipocyte differentiation. Therefore, our results indicated that ROS are an essential regulator of adipocyte differentiation in 3T3-L1 cells.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Insulin-stimulated lipid accumulation is inhibited by ROS-scavenging chemicals, but not by the Drp1 inhibitor Mdivi-1

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…ILG significantly attenuates protein expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein α, aP2, and glucose transporter type 4 in insulin-induced adipocyte differentiation. ILG inhibits lipid accumulation and inhibits the insulin-signaling pathway through protein-tyrosine phosphatase 1B activation, a negative regulator of the insulin signaling cascade in 3T3-L1 cells [ 13 ]. ILG also ameliorates plasma lipid levels, inhibits oxidative stress and inflammation, and attenuates atherosclerosis in apolipoprotein E-deficient mice [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice

Lee

Kwon

Choi

2018

IJMS

View full text Add to dashboard Cite

Isoliquiritigenin (ILG) is a flavonoid constituent of Glycyrrhizae plants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (w/w) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancing β-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.

show abstract

“…Wu et al demonstrated that ISL inhibits interferon γ induced inflammation in hepatocytes by influencing the activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK, and PI3K/Akt signaling pathways [14]. ISL blocks the ROS generation induced by insulin in 3T3-L1 cells and suppresses lipid accumulation [15]. Cao et al proved that ISL protects against oxidative stress in HepG2 cells by activating the nuclear factor erythroid 2-related factor (Nrf2) antioxidant response and increasing the expression of its target genes [16].…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice

Gesang

Cao

et al. 2016

IJMS

View full text Add to dashboard Cite

Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We sought to investigate the effects and mechanism of ISL on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE−/−) mice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), while it increased the expression of several lipoprotein-related genes in peritoneal macrophages treated with lipopolysaccharide (LPS). ISL also enhanced peroxisome proliferator-activated receptor gamma (PPARγ) protein levels and reversed the changes of ATP-binding cassette transporter A (ABCA1) and cluster of differentiation 36 (CD36) in macrophages treated with oxidative low-density lipoprotein (ox-LDL). Then, in an in vivo study, female apoE−/− mice were fed a Western diet with ISL (0, 20, 100 mg/kg/day) added for 12 weeks. We found that ISL decreased the plasma cholesterol levels of very low-density lipoprotein (VLDL)/LDL, promoted plasma superoxide dismutase (SOD) and paraoxonase-1 (PON1) activities, and decreased plasma IL-6, TNF-α, and MCP-1 levels. Moreover, ISL significantly reduced the atherosclerotic lesions and hepatic steatosis in apoE−/− mice. In the liver, ISL altered the expression of several key genes (such as SRBI, ABCA1, ABCG8, PPARγ, and FASN) involving cholesterol-selective uptake and excretion into bile, triglyceride (TG) biosynthesis, and inflammation. These results suggest that the atheroprotective effects of ISL are due to the improvement of lipid metabolism, antioxidation, and anti-inflammation, which involve PPARγ-dependent signaling.

show abstract

Isoliquiritigenin impairs insulin signaling and adipocyte differentiation through the inhibition of protein-tyrosine phosphatase 1B oxidation in 3T3-L1 preadipocytes

Cited by 18 publications

References 29 publications

Insulin-stimulated lipid accumulation is inhibited by ROS-scavenging chemicals, but not by the Drp1 inhibitor Mdivi-1

Insulin-stimulated lipid accumulation is inhibited by ROS-scavenging chemicals, but not by the Drp1 inhibitor Mdivi-1

Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice

Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice

Contact Info

Product

Resources

About