LKB1/AMPK pathway in the control of hepatic energy metabolism

Viollet, Benoı̂t; Foretz, Marc

doi:10.1002/9781118663387.ch23

Cited by 2 publications

(3 citation statements)

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“…The formations of the LKB1/STRAD/MO25 complex help to re-localize LKB1 from the nucleus to the cytoplasm [ 13 , 29 , 30 ]. It has been proposed that the heterotrimer complex is constitutively active, providing a continuous basal level of AMPK phosphorylation, and is further enhanced by conformational γ changes imposed by the binding of AMP to the subunit [ 31 ]. The phosphorylation of LKB1 at Ser431 reportedly does not affect the kinase activity itself, but is necessary for the formation of a heterotrimer complex and its translocation to the cytoplasm [ 12 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling

Liu

Dong

Wang

et al. 2023

IJMS

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6-Gingerol, one of the major pharmacologically active ingredients extracted from ginger, has been reported experimentally to exert hepatic protection in non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanism remains largely elusive. RNA sequencing indicated the significant involvement of the AMPK signaling pathway in 6-gingerol-induced alleviation of NAFLD in vivo. Given the significance of the LKB1/AMPK pathway in metabolic homeostasis, this study aims to investigate its role in 6-gingerol-induced mitigation on NAFLD. Our study showed that 6-gingerol ameliorated hepatic steatosis, inflammation and oxidative stress in vivo and in vitro. Further experiment validation suggested that 6-gingerol activated an LKB1/AMPK pathway cascade in vivo and in vitro. Co-immunoprecipitation analysis demonstrated that the 6-gingerol-elicited activation of an LKB1/AMPK pathway cascade was related to the enhanced stability of the LKB1/STRAD/MO25 complex. Furthermore, radicicol, an LKB1 destabilizer, inhibited the activating effect of 6-gingerol on an LKB1/AMPK pathway cascade via destabilizing LKB1/STRAD/MO25 complex stability in vitro, thus reversing the 6-gingerol-elicited ameliorative effect. In addition, molecular docking analysis further predicated the binding pockets of LKB1 necessary for binding with 6-gingerol. In conclusion, our results indicate that 6-gingerol plays an important role in regulating the stability of the LKB1/STRAD/MO25 complex and the activation of LKB1, which might weigh heavily in the 6-gingerol alleviation of NAFLD.

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Section: Discussionmentioning

confidence: 99%

6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling

Liu

Dong

Wang

et al. 2023

IJMS

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“…This is in agreement with the report of Rocchetti et al, who demonstrated that OLE might modulate gut microbiota and decrease satiety signal, leading to the inhibition of intestinal energy uptake [ 31 ]. On the other hand, all mammalians have the capacity to synthesize fatty acids de novo using glucose as the precursor to form TG and store in fat depots [ 32 ]. SREBP-1c is primarily responsible for the expression of genes including FAS and ACC, involved in de novo lipogenesis in the liver [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, all mammalians have the capacity to synthesize fatty acids de novo using glucose as the precursor to form TG and store in fat depots [ 32 ]. SREBP-1c is primarily responsible for the expression of genes including FAS and ACC, involved in de novo lipogenesis in the liver [ 32 ]. In accordance with the previous study [ 33 ], we found that the HFD diet promoted the expression of lipogenic genes.…”

Section: Discussionmentioning

confidence: 99%

Oleuropein-Rich Jasminum Grandiflorum Flower Extract Regulates the LKB1-PGC-1α Axis Related to the Attenuation of Hepatocellular Lipid Dysmetabolism

Hou,

Zhao,

Wang

et al. 2023

Nutrients

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Diets(饮食) rich in fat are a major(主要) cause(原因) of metabolic disease(疾病), and nutritional(营养) food has been widely(广泛) used(使用) to counteract the metabolic disorders such(这样) as obesity(肥胖) and fatty(脂肪) liver(肝). The present study investigated the effects of oleuropein-enriched extract(提取物) from Jasminum grandiflorum L. flowers (OLE-JGF) in high-fat diet(饮食) (HFD)-fed mice and oleic acid(酸) (OA)-treated AML-12 cells. Treatment(治疗) of HFD-fed mice with 0.6% OLE-JGF for 8 weeks significantly reduced body and liver(肝) weights, as well as attenuating lipid dysmetabolism and hepatic steatosis. OLE-JGF administration(政府当局) prominently suppressed the mRNA expressions(表达) of monocyte chemoattractant protein(蛋白)-1 (MCP-1) and cluster of differentiation 68 (CD68), and it also downregulated acetyl-CoA carboxylase (ACC) and fatty(脂肪) acid(酸) synthase (FAS) as well as sterol-regulatory-element(元素)-binding protein(蛋白) (SREBP-1c) in the liver(肝). Meanwhile, mitochondrial DNA and uncoupling protein(蛋白) 2 (UCP2) were upregulated along with the increased expression(表达) of mitochondrial biogenic promoters including liver(肝) kinase B1 (LKB1), peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α), nuclear(核) factor(因子)-erythroid-derived 2-like 2 (Nrf2), and mitochondrial transcription factor(因子) A (Tfam), but did not change AMP-activated protein(蛋白) kinase (AMPK) in liver(肝). The lipid droplets were decreased significantly after treatment(治疗) with 80 μM oleuropein for 24 h in OA-induced AML-12 cells. Furthermore, oleuropein significantly inhibited ACC mRNA expression(表达) and upregulated LKB1, PGC-1α, and Tfam mRNA levels, as well as increasing the binding level of LKB1 to PGC-1α promoter in OA-induced cells. These findings indicate(表明) that OLE-JGF reduces hepatic lipid deposition in HFD-fed mice, as well as the fact that OA-induced liver(肝) cells may be partly(部分) attributed to upregulation of the LKB1-PGC-1α axis, which mediates hepatic lipogenesis and mitochondrial biogenesis. Our study provides a scientific(科学) basis(基础) for the benefits and potential(潜在) use(使用) of the J. grandiflorum flower as a food supplement(补充) for the prevention(预防) and treatment(治疗) of metabolic disease(疾病).

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LKB1/AMPK pathway in the control of hepatic energy metabolism

Cited by 2 publications

References 111 publications

6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling

6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling

Oleuropein-Rich Jasminum Grandiflorum Flower Extract Regulates the LKB1-PGC-1α Axis Related to the Attenuation of Hepatocellular Lipid Dysmetabolism

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