6 results on '"Songtao Li"'
Search Results
2. tert-Butylhydroquinone (tBHQ) protects hepatocytes against lipotoxicity via inducing autophagy independently of Nrf2 activation
- Author
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Songtao Li, Chen Shen, Shan Sun, Jiaxin Li, Changhao Sun, Ximei Zhang, Michael Cho, and Zhenyuan Song
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Programmed cell death ,NF-E2-Related Factor 2 ,Fatty Acids ,Autophagy ,AMPK ,Hep G2 Cells ,Cell Biology ,AMP-Activated Protein Kinases ,Biology ,KEAP1 ,Antioxidants ,Article ,Hydroquinones ,Cell biology ,Mice ,Lipotoxicity ,Hepatocytes ,Animals ,Humans ,Protein kinase A ,Microtubule-Associated Proteins ,Molecular Biology ,PI3K/AKT/mTOR pathway ,CAMKK2 - Abstract
Saturated fatty acids (SFAs) induce hepatocyte cell death, wherein oxidative stress is mechanistically involved. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master transcriptional regulator of cellular antioxidant defense enzymes. Therefore, Nrf2 activation is regarded as an effective strategy against oxidative stress-triggered cellular damage. In this study, tert-butylhydroquinone (tBHQ), a widely used Nrf2 activator, was initially employed to investigate the potential protective role of Nrf2 activation in SFAs-induced hepatoxicity. As expected, SFAs-induced hepatocyte cell death was prevented by tBHQ in both AML-12 mouse hepatocytes and HepG2 human hepatoma cells. However, the protective effect of tBHQ is Nrf2-independent, because the siRNA-mediated Nrf2 silencing did not abrogate tBHQ-conferred protection. Alternatively, our results revealed that autophagy activation was critically involved in the protective effect of tBHQ on lipotoxicity. tBHQ induced autophagy activation and autophagy inhibitors abolished tBHQ’s protection. The induction of autophagy by tBHQ exposure was demonstrated by the increased accumulation of LC3 puncta, LC3-II conversion, and autophagic flux (LC3-II conversion in the presence of proteolysis inhibitors). Subsequent mechanistic investigation discovered that tBHQ exposure activated AMP-activated protein kinase (AMPK) and siRNA-mediated AMPK gene silencing abolished tBHQ-induced autophagy activation, indicating that AMPK is critically involved in tBHQ-triggered autophagy induction. Furthermore, our study provided evidence that tBHQ-induced autophagy activation is required for its Nrf2-activating property. Collectively, our data uncover a novel mechanism for tBHQ in protecting hepatocytes against SFAs-induced lipotoxicity. tBHQ-triggered autophagy induction contributes not only to its hepatoprotective effect, but also to its Nrf2-activating property.
- Published
- 2014
3. Nicotinamide protects hepatocytes against palmitate-induced lipotoxicity via SIRT1-dependent autophagy induction
- Author
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Songtao Li, Wang Ma, Zhenyuan Song, Chen Shen, Yue Ma, and Xiaobing Dou
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0301 basic medicine ,Niacinamide ,medicine.medical_specialty ,Programmed cell death ,Endocrinology, Diabetes and Metabolism ,Palmitates ,Pharmacology ,Biology ,Nicotinamide adenine dinucleotide ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Sirtuin 1 ,Internal medicine ,medicine ,Autophagy ,Humans ,Nutrition and Dietetics ,Nicotinamide ,Fatty Acids ,Hep G2 Cells ,Up-Regulation ,030104 developmental biology ,chemistry ,Lipotoxicity ,Saturated fatty acid ,Hepatocytes ,NAD+ kinase ,030217 neurology & neurosurgery ,Niacin - Abstract
Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism remains to be clearly elucidated. Palmitate is the most abundant SFA in the circulation and major lipotoxic inducer. Accumulating evidence supports that autophagy induction is protective against palmitate-induced cell death in a variety of cell types, including hepatocytes. Nicotinamide is the amide form of nicotinic acid (vitamin B3, Niacin) and a dietary supplementation as a source of vitamin B3. We previously reported that nicotinamide endowed hepatocytes resistance to palmitate-induced ER stress via up-regulating SIRT1, with cAMP/PKA/CREB pathway activation being a fundamental mechanism. This study was undertaken to investigate the potential anti-lipotoxic effect of nicotinamide and to elucidate underlying mechanism(s). Our data demonstrated that nicotinamide supplementation protected hepatocytes against palmitate-induced cell death. Mechanistic investigations revealed that nicotinamide supplementation activated autophagy in hepatocytes. Importantly, we showed that the anti-lipotoxic property of nicotinamide was abolished by autophagy inhibitors, suggesting that autophagy induction plays a mechanistic role in nicotinamide's anti-lipotoxic effect. Furthermore, we showed that SIRT1 inhibition blunted autophagy induction in response to nicotinamide supplementation and similarly abrogated the anti-lipotoxic effect conferred by nicotinamide supplementation. In conclusion, our data suggest that nicotinamide protects against palmitate-induced hepatotoxicity via SIRT1-dependent autophagy induction and that nicotinamide supplementation may represent a therapeutic choice for NAFLD.
- Published
- 2016
4. Increased 4-Hydroxynonenal Formation Contributes to Obesity-Related Lipolytic Activation in Adipocytes
- Author
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Ximei Zhang, Jiaxin Li, Dongfang Gu, Zhenyuan Song, Songtao Li, Chen Shen, and Zhigang Wang
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Male ,lcsh:Medicine ,Adipose tissue ,Hormone-sensitive lipase ,Biochemistry ,Second Messenger Systems ,Adenylyl cyclase ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Molecular Cell Biology ,Adipocytes ,Cyclic AMP ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,Protein Kinase Signaling Cascade ,Fatty Acids ,Lipids ,Signaling Cascades ,Second messenger system ,Medicine ,Metabolic Pathways ,Mitogen-Activated Protein Kinases ,Intracellular ,Research Article ,Signal Transduction ,Adenylyl Cyclases ,medicine.medical_specialty ,MAP Kinase Signaling System ,Lipolysis ,Biology ,03 medical and health sciences ,3T3-L1 Cells ,Internal medicine ,medicine ,Animals ,Humans ,Obesity ,Protein kinase A ,Triglycerides ,Nutrition ,030304 developmental biology ,Aldehydes ,Adenylate Kinase ,lcsh:R ,AMPK ,Cyclic AMP-Dependent Protein Kinases ,Cyclic Nucleotide Phosphodiesterases, Type 3 ,Mice, Inbred C57BL ,Metabolism ,Endocrinology ,chemistry ,Metabolic Disorders ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
Oxidative stress in adipose tissue plays an etiological role in a variety of obesity-related metabolic disorders. We previously reported that increased adipose tissue 4-hydroxynonenal (4-HNE) contents contributed to obesity-related plasma adiponectin decline in mice. In the present study, we investigated the effects of intracellular 4-HNE accumulation on lipolytic response in adipocytes/adipose tissues and underlying mechanisms. In both fully-differentiated 3T3-L1 and primary adipocytes, a 5-hour 4-HNE exposure elevated lipolytic reaction in a dose-dependent manner at both basal and isoproterenol-stimulated conditions, evidenced by significantly increased glycerol and fatty acids releases. This conclusion was corroborated by the comparable observations when the minced human visceral adipose tissues were used. Mechanistic investigations revealed that 4-HNE-stimulated lipolytic activation is multifactorial. 4-HNE exposure quickly increased intracellular cyclic AMP (cAMP) level, which was concomitant with increased phosphorylations of protein kinase A (PKA) and its direct downstream target, hormone sensitive lipase (HSL). Pre-incubation with H89, a potent PKA inhibitor, prevented 4-HNE stimulated glycerol release, suggesting that enhanced lipolytic action in response to 4-HNE increase is mediated mainly by cAMP/PKA signal pathway in adipocytes. In addition to activating cAMP/PKA/HSL pathway, 4-HNE exposure also suppresses AMP-activated protein kinase (AMPK), a suppressive pathway for lipolysis, measured by both Western blotting for phosphorylated form of AMPK and ELISA for enzyme activity. Furthermore, 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR), a pharmacological AMPK activator, alleviated 4-HNE-induced lipolysis, suggesting that AMPK suppression also contributes to 4-HNE elicited lipolytic response. In conclusion, our findings indicate that increased intracellular 4-HNE accumulation in adipocytes/adipose tissues contributes to obesity-related lipolytic activation.
- Published
- 2013
5. Sterol Regulatory Element--Binding Protein-1c Mediates Increase of Postprandial Stearic Acid, a Potential Target for Improving Insulin Resistance, in Hyperlipidemia.
- Author
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Xia Chu, Liyan Liu, Lixin Na, Huimin Lu, Songtao Li, Ying Li, and Changhao Sun
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INSULIN resistance ,DIABETES ,FATTY acids ,HYPERLIPIDEMIA ,CARBOXYLASES ,SMALL interfering RNA ,LABORATORY mice - Abstract
Elevated serum free fatty acids (FFAs) levels play an important role in the development of insulin resistance (IR) and diabetes. We investigated the dynamic changes and the underlying regulatory mechanism of postprandial FFA profile in hyperlipidemia (HLP) and their relation with insulin sensitivity in both humans and mice. We found that serum stearic acid (SA) is the only fatty acid that is increased dramatically in the postprandial state. The elevation of SA is due to increased insulin-stimulated de novo synthesis mediated by sterol regulatory element--binding protein-1c (SREBP-1c)/acetyl-CoA carboxylase/fatty acid synthase/elongation of long-chain fatty acid family member 6 (ELOVL6) and the elongation of palmitic acid (PA) catalyzed by ELOVL6. Downregulation of SREBP-1c or ELOVL6 by small interfering RNA can reduce SA synthesis in liver and serum SA level, followed by amelioration of IR in HLP mice. However, inhibition of SREBP-1c is more effective in improving IR than suppression of ELOVL6, which resulted in accumulation of PA. In summary, increased postprandial SA is caused by the insulin-stimulated SREBP-1c pathway and elongation of PA in HLP. Reduction of postprandial SA is a good candidate for improving IR, and SREBP-1c is potentially a better target to prevent IR and diabetes by decreasing SA. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
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6. Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK.
- Author
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Yucun Niu, Songtao Li, Lixin Na, Rennan Feng, Liyan Liu, Ying Li, and Changhao Sun
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MANGIFERIN , *FATTY acids , *BILIARY tract , *TRIGLYCERIDES , *BIOCHEMISTRY - Abstract
Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
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