scholarly journals Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xueying Liu ◽  
Zehong Yang ◽  
Huixuan Li ◽  
Wen Luo ◽  
Wentao Duan ◽  
...  
Keyword(s):  
Energy Consumption ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Obese Mice ◽  
Ampk Signaling ◽  
Ampk Pathway ◽  
Ucp1 Expression ◽  
White Fat

Chrysophanol, a primary active ingredient of Cassia mimosoides Linn or Rhei radix et rhizoma, has various pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory, as well as blood lipid regulation. However, whether chrysophanol can mitigate obesity, and its underlying mechanisms remains unclear. This study investigated whether chrysophanol effects energy metabolism in high-fat diet- (HFD-) induced obese mice and fat-specific Sirtuin 6- (SIRT6-) knockout (FKO) mice, targeting the SIRT6/AMPK signaling pathway in brown and white fat tissue. Our results showed that chrysophanol can effectively inhibit lipid accumulation in vitro and reduce mice’s body weight, improve insulin sensitivity and reduced fat content of mice, and induce energy consumption in HFD-induced obese mice by activating the SIRT6/AMPK pathway. However, a treatment with OSS-128167, an SIRT6 inhibitor, or si-SIRT6, SIRT6 target specific small interfering RNA, in vitro blocked chrysophanol inhibition of lipid accumulation. Similar results were obtained when blocking the AMPK pathway. Moreover, in the HFD-induced obese model with SIRT6 FKO mice, histological analysis and genetic test results showed that chrysophanol treatment did not reduce lipid droplets and upregulated the uncoupling protein 1 (UCP1) expression. Rather, it upregulated the expression of thermogenic genes and activated white fat breakdown by inducing phosphorylation of adenosine 5 ′ -monophosphate- (AMP-) activated protein kinase (AMPK), both in vitro and in vivo. OSS-128167 or si-SIRT6 blocked chrysophanol’s upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and Ucp1 expression. In conclusion, this study demonstrated that chrysophanol can activate brown fat through the SIRT6/AMPK pathway and increase energy consumption, insulin sensitivity, and heat production, thereby alleviating obesity and metabolic disorders.

scholarly journals Betatrophin knockdown induces beiging and mitochondria biogenesis of white adipocytes

2020 ◽  
Vol 245 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Zhe-Zhen Liao ◽  
Xiao-Yan Qi ◽  
Ya-Di Wang ◽  
Jiao-Yang Li ◽  
Qian-Qian Gu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ampk Signaling ◽  
White Adipocytes ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
Mitochondria Biogenesis ◽  
Paracrine Actions ◽  
White Fat

Remodeling of energy-storing white fat into energy-consuming beige fat has led to a promising new approach to alleviate adiposity. Several studies have shown adipokines can induce white adipose tissue (WAT) beiging through autocrine or paracrine actions. Betatrophin, a novel adipokine, has been linked to energy expenditure and lipolysis but not clearly clarified. Here, we using high-fat diet-induced obesity to determine how betatrophin modulate beiging and adiposity. We found that betatrophin-knockdown mice displayed less white fat mass and decreased plasma TG and NEFA levels. Consistently, inhibition of betatrophin leads to the phenotype change of adipocytes characterized by increased mitochondria contents, beige adipocytes and mitochondria biogenesis-specific markers both in vivo and in vitro. Of note, blocking AMP-activated protein kinase (AMPK) signaling pathway is able to abolish enhanced beige-like characteristics in betatrophin-knockdown adipocytes. Collectively, downregulation of betatrophin induces beiging in white adipocytes through activation of AMPK signaling pathway. These processes suggest betatrophin as a latent therapeutic target for obesity.

Ursolic acid alleviates lipid accumulation by activating the AMPK signaling pathway in vivo and in vitro

2020 ◽  
Vol 85 (11) ◽  
pp. 3998-4008
Author(s):  
Jing Cheng ◽  
Ying Liu ◽  
Yaojie Liu ◽  
Dong Liu ◽  
Yang Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ursolic Acid ◽  
Lipid Accumulation ◽  
Ampk Signaling

scholarly journals Neuroprotective effect of Estrogen Receptor α against neuroinflammation induced by hypoxia/ischemia via SIRT1-dependent AMPK pathway

2019 ◽  
Author(s):  
Z Z ◽  
He WQ ◽  
Cao XL ◽  
Tang B ◽  
Fan QY ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Nlrp3 Inflammasome ◽  
Neuroprotective Effect ◽  
Intraperitoneal Administration ◽  
Inflammasome Activation ◽  
In Vitro Production ◽  
Ampk Signaling ◽  
Ampk Pathway ◽  
Nlrp3 Inflammasome Activation

Abstract Background: Stroke-related damage in rats is protected against by estrogen which also has an anti-cerebral ischemia role mostly conducted via its association with estrogen receptor (ER) α .However,processes governing ER α-mediated neuroprotection are poorly comprehended. This study sought to establish whether ERα’s control of neuroinflammation caused by NLRP3 inflammasome activation emanating from SIRT1-AMPK signaling allowed ERα’s improvement of hypoxia/ischemic damage. Methods: The intraperitoneal administration of estrogen was performed to ovariectomized (bilaterally) (OVA) SD rats prior to middle cerebral artery occlusion (MCAO). The strong rise in NLRP3 inflammasome activation including caspase-1, ASC, IL-1β and IL-18 occurred following OVA and were specifically decreased following estrogen treatment. Moreover, the expression of Silent Information Regulator 1 (SIRT1) and ERα were reversed. The association between ERα-led inhibition of the NLRP3 inflammasome in conditions of hydrogen peroxide (H 2 O 2 ) and SIRT1-AMPK signaling were also examined. Results: Findings confirmed the prevention of NLRP3 inflammasome activation instigated by H 2 O 2 and the in vitro production of IL-1β, IL-18 together with the enhancement of this impact by SIRT1. Additionally, ERα's neuroprotective impact was prevented by inhibiting of AMPK. The synergistic impact of SIRT1 on ERα increased AMPK activation; however, SIRT1 knockout eliminated this. Conclusions: The findings indicate that inhibition of the NLRP3 inflammasome by ERα results in neuroprotection against hypoxia/ischemic injury and that ERα’s neuroprotection can be highly improved by the SIRT1-dependent AMPK pathway.

scholarly journals Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

2018 ◽  
Vol 49 (5) ◽  
pp. 1870-1884 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ciao-Han Wei ◽  
Ya-Ling Chen ◽  
Ching-Yi Cheng ◽  
Chia-Ling Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Epididymal Adipose Tissue ◽  
Obese Mice ◽  
High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

scholarly journals Glehnia littoralis Root Extract Inhibits Fat Accumulation in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice by Downregulating Adipogenic Gene Expression

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Heeok Hong ◽  
Joseph F. dela Cruz ◽  
Won Seob Kim ◽  
Kiyeol Yoo ◽  
Seong Gu Hwang
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Obese Mice ◽  
Intracellular Lipid ◽  
Glehnia Littoralis ◽  
Intracellular Lipid Accumulation ◽  
Adipogenic Gene

Glehnia littoralis has been reported to have several pharmacological properties but no reports describing the antiadipogenic effect of this plant have been published. This study was conducted to investigate the effects of Glehnia littoralis root hot water extract (GLE) and its underlying mechanism on 3T3-L1 cell adipogenesis and in high-fat diet- (HFD-) induced obese mice. We measured intracellular lipid accumulation using oil red O staining in vitro. For in vivo study, twenty-eight C57BL/6J male mice were randomly divided into four groups, Control, HFD, HFD + 1% GLE, and HFD + 5% GLE, which was performed for eight weeks. We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo.

Glucagon attenuates lipid accumulation in cow hepatocytes through AMPK signaling pathway activation

2018 ◽  
Vol 234 (5) ◽  
pp. 6054-6066 ◽  
Author(s):  
Yu Li ◽  
Hongyan Ding ◽  
Jihong Dong ◽  
Sajid Ur Rahman ◽  
Shibin Feng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Ampk Signaling ◽  
Pathway Activation

scholarly journals Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 993 ◽  
Author(s):  
Hairui Yang ◽  
Xu Bai ◽  
Henan Zhang ◽  
Jingsong Zhang ◽  
Yingying Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Lung Carcinoma ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Clinical Pharmacokinetics ◽  
Ampk Signaling ◽  
P53 Signaling ◽  
Lung Carcinoma Cells

The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and arrested the cell cycle at the G2/M phase via a P53 signaling pathway. Interestingly, phenomena such as autophagosomes accumulation, conversion of the LC3-I to LC3-II, etc., indicated that autophagy could be activated by ADC. The blockage of autophagy-augmented ADC induced inhibition of cell proliferation, while autophagy activation restored cell death, indicating that autophagy had a protective effect against cell death which was induced by ADC treatment. Meanwhile, ADC treatment suppressed both the Akt/mTOR and AMPK signaling pathways. The joint action of both ADC and the autophagy inhibitor significantly increased the death of SPCA-1. An in vitro phase I metabolic stability assay showed that ADC was highly metabolized in SD rat liver microsomes and moderately metabolized in human liver microsomes, which will assist in predicting the outcomes of clinical pharmacokinetics and toxicity studies. These findings imply that blocking the Akt/mTOR signaling pathway, which was independent of AMPK inhibition, could activate ADC-induced protective autophagy in non-small-cell lung cancer cells.

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