Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds.

Fabiola Marín-Aguilar,Luis Pavillard,Pedro Bullón,Mario Cordero,Francesca Giampieri

doi:10.3390/ijms18020288

Abstract

Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor which is activated by increases in adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio and/or adenosine diphosphate (ADP)/ATP ratio, and increases different metabolic pathways such as fatty acid oxidation, glucose transport and mitochondrial biogenesis. In this sense, AMPK maintains cellular energy homeostasis by induction of catabolism and inhibition of ATP-consuming biosynthetic pathways to preserve ATP levels. Several studies indicate a reduction of AMPK sensitivity to cellular stress during aging and this could impair the downstream signaling and the maintenance of the cellular energy balance and the stress resistance. However, several diseases have been related with an AMPK dysfunction. Alterations in AMPK signaling decrease mitochondrial biogenesis, increase cellular stress and induce inflammation, which are typical events of the aging process and have been associated to several pathological processes. In this sense, in the last few years AMPK has been identified as a very interesting target and different nutraceutical compounds are being studied for an interesting potential effect on AMPK induction. In this review, we will evaluate the interaction of the different nutraceutical compounds to induce the AMPK phosphorylation and the applications in diseases such as cancer, type II diabetes, neurodegenerative diseases or cardiovascular diseases.

Highlights

Adenosine monophosphate-activated protein kinase (AMPK), is a heterotrimeric protein kinase consisting of an alpha (α) catalytic subunit in combination with scaffolding beta (β) and regulatory gamma (γ) subunits (Figure 1)
These subunits, encoded by seven genes: Protein Kinase adenosine monophosphate (AMP)-Activated Catalytic Subunit α1 (PRKAA1), Protein Kinase AMP-Activated Catalytic Subunit α2 (PRKAA2), Protein Kinase AMP-Activated Non-Catalytic Subunit β1 (PRKAB1), Protein Kinase AMP-Activated Non-Catalytic Subunit β2 (PRKAB2), Protein Kinase AMP-Activated Non-Catalytic Subunit γ1 (PRKAG1), Protein Kinase AMP-Activated Non-Catalytic Subunit γ2 (PRKAG2), Protein Kinase AMP-Activated Non-Catalytic Subunit γ3 (PRKAG3) can theoretically combine to form twelve different possible isoforms that may differ in tissue-specific expression and activation
AMPK is known as the fuel of the cell, working to ensure that adenosine triphosphate (ATP) levels are maintained under energetic stress situations such as exercise, starvation, hypoxia or rapid cell growth [1]

Summary

Introduction

Adenosine monophosphate-activated protein kinase (AMPK), is a heterotrimeric protein kinase consisting of an alpha (α) catalytic subunit in combination with scaffolding beta (β) and regulatory gamma (γ) subunits (Figure 1). The interest of the scientific community in targeting the activation of AMPK pathway as a new treatment for metabolic disorders has arisen as a result of the value of this kinase in managing cellular metabolism and energy control Phenolic compounds such as quercetin and resveratrol (Table 3), have shown an increased glucose uptake in muscle cells and adipocytes by promoting translocation of GLUT4 via induction of AMPK in vitro [63,64]. These findings suggest that quercetin constitutes a nutraceutical compound able to ameliorate insulin resistance in muscle cells through different events linked to AMPK phosphorylation and activation [87] Phenolic alcohols, such as hydroxytyroxol (Table 3) were found to increase fatty acid oxidation and to improve insulin sensitivity through AMPK phosphorylation, as shown in 3T3-L1 adipocytes, suggesting its possible involvement in diabetes mellitus management [88]. Berberine has shown some favorable effects on plasma glucose, lipids and glycated haemoglobin (HbA1c) (Table 3) in two clinical trials performed in patients newly diagnosed with type 2 diabetes [83]

Nutraceutical Compounds and Neurodegenerative Diseases

Autophagy-Mediated and rice

Conclusions