AMPK against NASH

Strzyz, Paulina

doi:10.1038/s41580-020-0225-0

Cited by 28 publications

(21 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The top 15 of those additional and unique pathways of combination therapy are depicted in Fig. 5B and demonstrate a mixture of inflammatory pathways (CCR5 signalling in macrophages), cancer-related and several other pathways including for NASH interesting pathways like hepatic fibrosis signalling pathway, WAT browning pathway and AMP-activated protein kinase (AMPK) signalling pathway, the latter signalling on an important cellular energy sensor that is a novel target for pharmaceutical treatment of hepatic fibrosis [39,40].…”

Section: Exercise Diet Change and Combination Intervention Have Differential Effects On Transcriptomic Profilementioning

confidence: 99%

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

et al. 2021

View full text Add to dashboard Cite

Background: Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5-7%) can already have a beneficial effect on NASH. However, the underlying molecular mechanisms of exercise and diet interventions remain largely elusive, and it is unclear whether they exert their health effects via similar or different pathways. Methods: Ldlr−/−.Leiden mice received a high fat diet (HFD) for 30 weeks to establish a severe state of NASH/ fibrosis with simultaneous atherosclerosis development. Groups of mice were then either left untreated (control group) or were treated for 20 weeks with exercise (running wheel), diet change (switch to a low fat chow diet) or the combination thereof. The liver and distant organs including heart, white adipose tissue (WAT) and muscle were histologically examined. Comprehensive transcriptome analysis of liver, WAT and muscle revealed the organ-specific effects of exercise and diet and defined the underlying pathways. Results: Exercise and dietary change significantly reduced body weight, fat mass, adipocyte size and improved myosteatosis and muscle function with additive effects of combination treatment. WAT inflammation was significantly improved by diet change, tended to be reduced with exercise, and combination therapy had no additive effect. Hepatic steatosis and inflammation were almost fully reversed by exercise and diet change, while hepatic fibrosis tended to be improved with exercise and was significantly improved with diet change. Additive effects for the combination therapy were shown for liver steatosis and associated liver lipids, and atherosclerosis, but not for hepatic inflammation and fibrosis. Pathway analysis revealed complementary effects on metabolic pathways and lipid handling processes, thereby substantiating the added value of combined lifestyle treatment. Conclusions: Exercise, diet change and the combination thereof can reverse established NASH/fibrosis in obese Ldlr−/−.Leiden mice. In addition, the lifestyle interventions had beneficial effects on atherosclerosis, WAT inflammation and muscle function. For steatosis and other parameters related to adiposity or lipid metabolism, exercise and dietary change affected more distinct pathways that acted complementary when the interventions were combined resulting in an additive effect for the combination therapy on important endpoints including NASH and atherosclerosis. For inflammation, exercise and diet change shared several underlying pathways resulting in a net similar effect when the interventions were combined.

show abstract

Section: Exercise Diet Change and Combination Intervention Have Differential Effects On Transcriptomic Profilementioning

confidence: 99%

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

et al. 2021

View full text Add to dashboard Cite

show abstract

“…With the continuous improvement of living standards and the change in diet, the incidence of nonalcoholic fatty liver disease (NAFLD) has increased, ranging from simple fatty liver (SFL) to nonalcoholic steatohepatitis (NASH), and became the most common and complex chronic liver disease, affecting 25% of adults globally [ 1 ]. In general, NASH, which is characterized by hepatic steatosis, chronic inflammation, oxidative stress, and fibrosis in hepatocytes and is caused by the uncontrolled development of SFL, and it is a precursor of numerous serious liver diseases, including hepatocellular carcinoma and cirrhosis [ 2 ]. Interestingly, there is a significant gender distinguishment in the severity and morbidity of NASH.…”

Section: Introductionmentioning

confidence: 99%

The sex steroid precursor dehydroepiandrosterone prevents nonalcoholic steatohepatitis by activating the AMPK pathway mediated by GPR30

Wang

Yao

et al. 2021

Redox Biology

View full text Add to dashboard Cite

“…The occurrence of NASH was always characterized by lipid accumulation and inflammation (Schuster et al, 2018;Tomita et al, 2016). Certain evidence indicated AMPK (AMP-activated protein kinase) was a central energy mediator in NASH, which decreased NF-κB pathway and activated mitochondrial biogenesis (Herzig & Shaw, 2018;Liu et al, 2011;Strzyz, 2020;Wang et al, 2017). Differed from the above findings, STAT1 (signal transducers and activators of transcription) and CXCL10 (macrophage chemotactic ligand 10) could be regarded as potential targets for suppressing NASH in our present study.…”

Section: Introductionmentioning

confidence: 59%

Diosmetin modulates lipogenesis and alleviates inflammatory response in nonalcoholic steatohepatitis through STAT1/CXCL10-dependent pathway

Luo¹,

Yang²,

Zhu³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background and Purpose: Diosmetin (Dios) exerted a hepatoprotective effect against nonalcoholic steatohepatitis (NASH), but few reports interpreted clearly that the alleviation of Dios against NASH were associated with the inhibition of signal transducers and activators of transcription 1 (STAT1) and macrophage chemotactic ligand 10 (CXCL10). Meanwhile, the mechanism of Dios involved with STAT1/CXCL10 mediated pathway was unknown yet. Experimental Approach: Here, high-fat diet (HFD) and palmitic acid (PA) were used to induced NASH model in mice and HepG2 cells, respectively. The liver RNA-Seq was used to reveal the key targets interfered by Dios. The impacts of Dios on the expressions of STAT1, CXCL10 and the levels of genes and proteins associated with lipogenesis and inflammation were measured by qRT-PCR and western blot assays. The STAT1 inhibitor, STAT1 overexpression plasmid, and CXCL10 siRNA were utilized to clarify the mechanism of Dios against NASH through STAT1 / CXCL10. Key Results: Dios could reduce functional parameters and morphological changes in HepG2 cells and NASH mice. Additionally, Dios alleviated the expressions of key targets STAT1 and CXCL10, and their downstream proteins involved with lipogenesis and inflammation. Interestingly, NASH was ameliorated in STAT1-inhibited mice and HepG2 cells. Unfortunately, transfecting HepG2 cells with STAT1 over-expression plasmid aggravated the development of NASH and reduced Dios-conferred hepatoprotective effect. Conclusions and Implications: The alleviation of Dios against NASH was through mediation of lipogenesis and inflammatory response via STAT1/CXCL10-dependent pathway. Therefore, Dios has good hepatoprotective effects and potentiality as a promising therapeutic agent for NASH in clinical application.

show abstract

AMPK against NASH

Cited by 28 publications

References 2 publications

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

The sex steroid precursor dehydroepiandrosterone prevents nonalcoholic steatohepatitis by activating the AMPK pathway mediated by GPR30

Diosmetin modulates lipogenesis and alleviates inflammatory response in nonalcoholic steatohepatitis through STAT1/CXCL10-dependent pathway

Contact Info

Product

Resources

About