Fucoxanthin attenuates fatty acid-induced lipid accumulation in FL83B hepatocytes through regulated Sirt1/AMPK signaling pathway

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.

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Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway

International Journal of Obesity ◽

10.1038/ijo.2015.199 ◽

2015 ◽

Vol 40 (3) ◽

pp. 443-451 ◽

Cited By ~ 90

Author(s):

C Xin ◽

J Liu ◽

J Zhang ◽

D Zhu ◽

H Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acid ◽

Signaling Pathway ◽

Fatty Acid Oxidation ◽

Glucose Utilization ◽

Acid Oxidation ◽

Ampk Signaling

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7374086 ◽

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.

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Vanadium(IV)-chlorodipicolinate alleviates hepatic lipid accumulation by inducing autophagy via the LKB1/AMPK signaling pathway in vitro and in vivo

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2018.03.006 ◽

2018 ◽

Vol 183 ◽

pp. 66-76 ◽

Cited By ~ 8

Author(s):

Ying Huang ◽

Fang Liu ◽

Fang Zhang ◽

Pingsheng Liu ◽

Tao Xu ◽

...

Keyword(s):

Signaling Pathway ◽

Lipid Accumulation ◽

Hepatic Lipid ◽

Ampk Signaling ◽

Hepatic Lipid Accumulation

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L-theanine Prevents Progression of Nonalcoholichepatic Steatosis by Regulating Hepatocyte Lipid Metabolic Pathways via the CaMKKβ-AMPK Signaling Pathway

10.21203/rs.3.rs-820686/v1 ◽

2021 ◽

Author(s):

Juanjuan Liang ◽

Lili Gu ◽

Xianli Liu ◽

Xintong Yan ◽

Xiaowen Bi ◽

...

Keyword(s):

Fatty Acid ◽

Protein Kinase ◽

Signaling Pathway ◽

Hepatic Steatosis ◽

Metabolic Pathways ◽

Alcoholic Fatty Liver ◽

Ampk Signaling ◽

Nonalcoholic Hepatic Steatosis

Abstract Background: L-theanine, a non-protein amino acid found principally in the green tea, has been previously shown to possess potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism. Methods: In vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high‐fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of TG, accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo.Results: Our data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced Non-alcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator–activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK via its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ). Conclusions: Taken together, our findings suggest that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway.

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