Dapagliflozin attenuates steatosis in livers of high-fat diet-induced mice and oleic acid-treated L02 cells via regulating AMPK/mTOR pathway

2021 ◽  
pp. 174304
Author(s):  
Jingyi Luo ◽  
Pengbo Sun ◽  
Yangyang Wang ◽  
Yang Chen ◽  
Yaoyun Niu ◽  
...  
2021 ◽  
Author(s):  
Jingda Li ◽  
Tianqi Wang ◽  
Panpan Liu ◽  
Fuyuan Yang ◽  
Xudong Wang ◽  
...  

Hesperetin as a major bioflavonoid in citrus fruits improves NAFLD by suppressing hepatic oxidative stress and inflammation.


2015 ◽  
Vol 309 (11) ◽  
pp. E925-E935 ◽  
Author(s):  
Li Sun ◽  
Song Zhang ◽  
Chengyuan Yu ◽  
Zhenwei Pan ◽  
Yang Liu ◽  
...  

Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPKα2−/− mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPK-mTOR pathway.


1994 ◽  
Vol 109 (1-2) ◽  
pp. 144
Author(s):  
F. Pe´rez-Jime´nez ◽  
J. Lo´pez-Miranda ◽  
J. Trujillo ◽  
A. Blanco-Molina ◽  
J. Blanco ◽  
...  

2010 ◽  
Vol 33 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Liqun Ma ◽  
Shuangtao Ma ◽  
Hongbo He ◽  
Dachun Yang ◽  
Xiaoping Chen ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Camila O. Souza ◽  
Alexandre A. S. Teixeira ◽  
Edson A. Lima ◽  
Helena A. P. Batatinha ◽  
Lara M. Gomes ◽  
...  

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-αdependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF𝜅B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.


Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3085
Author(s):  
Mo Yang ◽  
Dong Hu ◽  
Zhengying Cui ◽  
Hongxuan Li ◽  
Chaoxin Man ◽  
...  

Excessive lipid intake will cause hyperlipidemia, fatty liver metabolism disease, and endanger people’s health. Edible fungus polysaccharide is a natural active substance for lipid lowering. In this study, the HepG2 cell model induced by oleic acid and mice model induced by a high-fat diet was established. The lipid-lowering effects of Inonotus obliquus polysaccharide (IOP) was investigated in vivo and in vitro. Glucose (251.33 mg/g), rhamnose (11.53 mg/g), ribose (5.10 mg/g), glucuronic acid (6.30 mg/g), and galacturonic acid (2.95 mg/g) are present in IOP, at a ratio of 85.2:3.91:1.73:2.14:1. The molecular weight of IOP is 42.28 kDa. Treatment with 60 mg/L of IOP showed a significant lipid-lowering effect in HepG2 cells compared with the oleic acid-treated group. In the oil red O-stained images, the red fat droplets in the IOP-treated groups were significantly reduced. TC and TG levels of IOP-treated groups decreased. IOP can alleviate the lipid deposition in the mice liver due to high-fat diet, and significantly reduce their serum TC, TG, and LDL-C contents. IOP could activate AMPK but decrease the SREBP-1C, FAS, and ACC protein expression related to adipose synthesis in mice. IOP has a certain potential for lipid-lowering effects both in vivo and in vitro.


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 751 ◽  
Author(s):  
Wu ◽  
Wei ◽  
Yang ◽  
Zhao ◽  
Luo

The autophagy-lysosome pathway, which involves many crucial genes and proteins, plays crucial roles in the maintenance of intracellular homeostasis by the degradation of damaged components. At present, some of these genes and proteins have been identified but their specific functions are largely unknown. This study was performed to clone and characterize the full-length cDNA sequences of nine key autolysosome-related genes (vps11, vps16, vps18, vps33b, vps41, lamp1, mcoln1, ctsd1 and tfeb) from yellow catfish Pelteobagrus fulvidraco. The expression of these genes and the transcriptional responses to a high-fat diet and fatty acids (FAs) (palmitic acid (PA) and oleic acid (OA)) were investigated. The mRNAs of these genes could be detected in heart, liver, muscle, spleen, brain, mesenteric adipose tissue, intestine, kidney and ovary, but varied with the tissues. In the liver, the mRNA levels of the nine autolysosome-related genes were lower in fish fed a high-fat diet than those fed the control, indicating that a high-fat diet inhibited formation of autolysosomes. Palmitic acid (a saturated FA) significantly inhibited the formation of autolysosomes at 12 h, 24 h and 48 h incubation. In contrast, oleic acid (an unsaturated FA) significantly induced the formation of autolysosomes at 12 h, but inhibited them at 24 h. At 48 h, the effects of OA incubation on autolysosomes were OA concentration-dependent in primary hepatocytes of P. fulvidraco. The results of flow cytometry and laser confocal observations confirmed these results. PA and OA incubation also increased intracellular non-esterified fatty acid (NEFA) concentration at 12 h, 24 h and 48 h, and influenced mRNA levels of fatty acid binding protein (fabp) and fatty acid transport protein 4 (fatp4) which facilitate FA transport in primary hepatocytes of P. fulvidraco. The present study demonstrated the molecular characterization of the nine autolysosome-related genes and their transcriptional responses to fat and FAs in fish, which provides the basis for further exploring their regulatory mechanism in vertebrates.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Juan Li ◽  
Lv Zhu ◽  
Yu-mei Zhang ◽  
Huan Chen ◽  
Yi-fan Miao ◽  
...  

Background and Aims. Nonalcoholic fatty liver disease (NAFLD) is an alarming public health problem that directly contributes to increased prevalence of liver cirrhosis and hepatic cell cancer, but without any specific pharmacological option. Sheng-jiang powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great efficacy but the specific mechanisms have never been reported. Therefore, we performed this study to explore the effect of SJP on NAFLD and the potential mechanism.Methods. NAFLD was induced by high fat diet (HFD) feeding. Rats were treated with SJP/normal saline daily for 10 weeks and all rats were euthanized after 12 weeks’ feeding. Liver tissue samples were obtained for biochemistry test and pathological evaluation. Additionally, oleic acid induced LO2 cells were employed to simulate a cell model of NAFLD. Cells were subjected to western blotting for Akt, mTOR, S6, SREBP1-c, and FASN detection after coincubated with SJP, LY294002 (a selective PI3K inhibitor), or the combination for 24h.Results. HFD significantly induced hepatic steatosis. Plenty of lipid droplets were observed under transmission electron microscope. The ultrastructure of liver cells showed distinct changes with obvious endoplasmic reticulum expansion, mitochondrial contraction, and cell matrix solidification. Although no difference was detected in serum hepatic enzymes and tissue proinflammatory cytokines, the tissue level of SOD and GSH-px was much lower and the pathologic injuries were much severe in HFD feeding rats. However, SJP treatment significantly attenuated the ultrastructure changes and protected rat liver against inflammatory injury. Abundant of lipid droplets and high expression of pAkt, pmTOR, pS6, and FASN were observed in oleic acid treated LO2 cells, while these changes were restored by SJP treatment.Conclusions. SJP is efficient in attenuating HFD induced NAFLD in rats and this effect might be partly related to the inhibition of Akt/mTOR/S6 pathway.


1999 ◽  
Vol 277 (1) ◽  
pp. R279-R285 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter

When rats are maintained on high-fat diets, digestive processes adapt to provide for more efficient digestion and absorption of this nutrient. Furthermore, rats fed high-fat diets tend to consume more calories and gain more weight than rats on a low-fat diet. We hypothesized that, in addition to adaptation of digestive processes, high-fat maintenance diets might result in reduction of sensitivity to the satiating effects of fat digestion products, which inhibit food intake by activating sensory fibers in the small intestine. To test this hypothesis we measured food intake after intestinal infusion of oleic acid or the oligosaccharide maltotriose in rats maintained on a low-fat diet or one of three high-fat diets. We found that rats fed high-fat diets exhibited diminished sensitivity to satiation by intestinal infusion of oleic acid. Sensitivity to the satiation effect of intestinal maltotriose infusion did not differ between groups maintained on the various diets. Reduced sensitivity to oleate infusion was specifically dependent on fat content of the diet and was not influenced by the dietary fiber or carbohydrate content. These results indicate that diets high in fat reduce the ability of fat to inhibit further food intake. Such changes in sensitivity to intestinal fats might contribute to the increased food intake and obesity that occur with high-fat diet regimens.


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