Nutritional Modulation of AMPK-Impact upon Metabolic-Inflammation

Lyons, Claire L.; Roche, Helen M.

doi:10.3390/ijms19103092

Cited by 122 publications

(88 citation statements)

References 99 publications

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“…AMPK is one of the most important energy sensors identified so far that can regulate the cellular metabolism. Similarly, AMPK inhibits a broad range of inflammatory reactions through multiple biological pathways by regulating immune cell metabolism and functions (41,42). In our current study, no obvious differences in the serum levels of AMPK-α1 and p-AMPK-α1 between OA and RA patients were observed.…”

Section: Discussioncontrasting

confidence: 46%

Adenosine monophosphate-activated protein kinase activator inhibits activation of fibroblast-like synoviocytes but promotes hyaluronan and proteoglycan link protein 1 secretion

Chen

Fujuan

Beijia

et al. 2020

Preprint

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Objectives: To determine whether any correlation exists between disease activity and AMPK levels in rheumatoid arthritis (RA) patients and investigate the effects of AMPK activator treatment on RA fibroblast-like synoviocytes (RA-FLS).Methods: Serum AMPK-α1, p-AMPK-α1, TNF-α and IL-17 levels between osteoarthritis (OA) and RA patients having different disease activities were compared by ELISA. Differentially expressed genes (DEGs) between RA and OA synovium from NCBI GEO Profiles (accession numbers: GSE1202112, GSE55235, GSE5545713) were identified and the genes intersecting in all the three datasets were selected for enrichment analysis. Immunohistochemical staining was done with synovium obtained from OA and RA patients for p-AMPK-α1. AMPK gene expression in synovium was semi-quantified by RT-qPCR. RNA sequencing of FLS was performed and DEGs were selected for KEGG enrichment analysis. AMPK activator, metformin, treated RA-FLS were tested for proliferation and migration by MTT and scratch test, respectively. Expression of IL-6, AMPK-α1, PKA-α, RAPTOR, mTOR, HAPLN1, RUNX1 and RUNX2 genes were determined by qPCR. Phosphorylated AMPK-α1 and HAPLN1 levels were determined by an automated electrophoresis-western blot analysis method.Results: In RA sera, a positive correlation between p-AMPK-α1 levels and DAS28 (r = 0.270, 95%CI: 0.142-0.492, p < 0.0001) as well as CRP levels (r = 0.259, 95%CI: 0.009-0.478, p < 0.05) was found. Similarly, a positive correlation was observed between AMPK-α1 and TNF-α levels (r = 0.460, 95% CI: 0.241-0.640, p = 0.0002). DEGs between OA and RA synovium from NCBI GEO profiles and our RNA sequencing data suggested activation of metabolic pathways specific to RA-FLS. AMPK-α1 was highly expressed in the synovium of RA but not OA patients. Metformin at higher concentrations inhibited RA-FLS proliferation in a dose dependant manner, however, at lower concentrations it has an opposite effect. On the other hand, AMPK inhibitor, dorsmophin, promoted the proliferation of RA-FLS significantly. Interestingly, both metformin and dorsmophin substantially inhibited the migration of RA-FLS. In FLS, relative expression level of IL-6 mRNA was significantly decreased after metformin treatment, while the expression of AMPK-α1, PKA-α and HAPLN1 genes were significantly increased. Western blot analysis confirmed increased expression of p-AMPK-α1 and HAPLN1 genes in the metformin treated FLS.Conclusions: Inflammatory stress in RA synovium leads to an increase in AMPK levels, possibly as a protective mechanism. AMPK activator but not metformin per se could be a potential therapeutic for RA by promoting HAPLN1 secretion to protect the joints.

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Section: Discussioncontrasting

confidence: 46%

Adenosine monophosphate-activated protein kinase activator inhibits activation of fibroblast-like synoviocytes but promotes hyaluronan and proteoglycan link protein 1 secretion

Chen

Fujuan

Beijia

et al. 2020

Preprint

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“…Another therapeutic target for obesity could be AMPK, a signaling protein involved in adapting cellular metabolism in response to nutritional variations. [30] Previous in vitro studies with 3T3-L1-adipocytes have shown a beneficial effect of Lippia citriodora polyphenols on decreasing triglyceride accumulation and reducing ROS generation, which was linked to AMPK modulation. [24] In the present study, HFD-fed mice showed a reduced expression of Ampk in the adipose tissue, which was but completely restored by LCE treatment (Figure 2B).…”

Section: Effects Of Lce On Inflammatory Status and Gut Dysbiosismentioning

confidence: 99%

The Beneficial Effects of Lippia Citriodora Extract on Diet‐Induced Obesity in Mice Are Associated with Modulation in the Gut Microbiota Composition

Diez-Echave

Vezza

Rodríguez-Nogales

et al. 2020

Molecular Nutrition Food Res

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Scope Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well‐characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome. Methods Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg−1). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium‐dependent vasodilator response to acetylcholine. Results LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice. Conclusion The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.

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“…More recently, the treatment of db/db mice with an activator of adiponectin, AdipoRon, showed the upregulation of phosphorylated AMPK in the kidney along with reduced inflammation and lipotoxicity [30]. Finally, obesity and diabetes are associated with inflammation and oxidative stress that are both recognized to inhibit AMPK [61]. The pro-inflammatory cytokine TNFα is known to suppress AMPK activity via the induction of protein phosphatase 2C (PP2C) in skeletal muscle in vitro and in vivo, suppressing fatty acid (FA) oxidation and promoting insulin resistance [62].…”

Section: Ampk Activity In Obesity and Diabetes-induced Chronic Kidneymentioning

confidence: 99%

Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease

Juszczak

Caron

Mathew

et al. 2020

IJMS

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Chronic kidney disease (CKD) is prevalent in 9.1% of the global population and is a significant public health problem associated with increased morbidity and mortality. CKD is associated with highly prevalent physiological and metabolic disturbances such as hypertension, obesity, insulin resistance, cardiovascular disease, and aging, which are also risk factors for CKD pathogenesis and progression. Podocytes and proximal tubular cells of the kidney strongly express AMP-activated protein kinase (AMPK). AMPK plays essential roles in glucose and lipid metabolism, cell survival, growth, and inflammation. Thus, metabolic disease-induced renal diseases like obesity-related and diabetic chronic kidney disease demonstrate dysregulated AMPK in the kidney. Activating AMPK ameliorates the pathological and phenotypical features of both diseases. As a metabolic sensor, AMPK regulates active tubular transport and helps renal cells to survive low energy states. AMPK also exerts a key role in mitochondrial homeostasis and is known to regulate autophagy in mammalian cells. While the nutrient-sensing role of AMPK is critical in determining the fate of renal cells, the role of AMPK in kidney autophagy and mitochondrial quality control leading to pathology in metabolic disease-related CKD is not very clear and needs further investigation. This review highlights the crucial role of AMPK in renal cell dysfunction associated with metabolic diseases and aims to expand therapeutic strategies by understanding the molecular and cellular processes underlying CKD.

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Nutritional Modulation of AMPK-Impact upon Metabolic-Inflammation

Cited by 122 publications

References 99 publications

Adenosine monophosphate-activated protein kinase activator inhibits activation of fibroblast-like synoviocytes but promotes hyaluronan and proteoglycan link protein 1 secretion

Adenosine monophosphate-activated protein kinase activator inhibits activation of fibroblast-like synoviocytes but promotes hyaluronan and proteoglycan link protein 1 secretion

The Beneficial Effects of Lippia Citriodora Extract on Diet‐Induced Obesity in Mice Are Associated with Modulation in the Gut Microbiota Composition

Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease

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