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

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.

MD-1, a poly herbal formulation indicated in diabetes mellitus ameliorates glucose uptake and inhibits adipogenesis – an in vitro study

“…The enhanced glucose uptake by HAEF is suggesting the beneficial effect of MD-1 supplementation in insulin resistance. Presence of phytochemicals like gallic acid [41], ellagic acid [42], berberine [43] and quercetin [44] with reported activation of AMPK pathway substantiated the observed glucose uptake by MD-1 in the absence of insulin. Reported amelioration of insulin resistance by the constituent herbs [45, 46] lends support to the HAEF mediated 2-DG uptake in the presence of insulin.…”

Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation

“…AMPK phosphorylates many proteins involved in autophagy regulation as well as proteins implicated in the control of cell cycle and apoptosis, like p21 and p53, strongly suppressing cell proliferation [ 20 ]. In the last few years AMPK has been identified as a target of several nutraceutical compounds that increase AMPK phosphorylation to modulate many cell functions [ 21 ]. To investigate whether capsaicin modulates AMPK and to examine the mechanism underpinning the cytotoxicity by capsaicin, we analyzed the activation of AMPK in HCC cells.…”

Ethanol extracts of <i>Aster yomena</i> (Kitam.) Honda inhibit adipogenesis through the activation of the AMPK signaling pathway in 3T3-L1 preadipocytes

“…During preadipocyte differentiation and adipogenesis, AMPK is inactivated by lower phosphorylation levels (17,19). In addition, AMPK activation by phosphorylation can reduce the degree of obesity by inhibiting adipocyte differentiation by changing the expression and activity of the enzymes and proteins involved in lipid metabolism (16,19).…”

“…The activation of AMKP inhibits preadipocyte differentiation and adipogenesis through increased phosphorylation of ACC, a substrate of AMPK (13,17). To investigate whether AMPK is activated by EEAY during 3T3-L1 differentiation, we analyzed the levels of phosphorylated AMPK and ACC and found that EEAY remarkably enhanced the phosphorylation of AMPK and ACC without altering the expression of their total protein expression, indicating the activation of the AMPK pathway.…”

“…Once AMPK is activated via phosphorylation by the upstream AMPK kinases, it functions as a cellular energy sensor through the regulation of fatty acid and glucose homeostasis (16,17). The activated AMPK increases glucose transport and fatty acid oxidation; it also inhibits the energy-consuming processes such as lipogenesis, protein synthesis, and gluconeogenesis (18,19).…”