Therapeutic Properties of Polyphenols Affect AMPK Molecular Pathway in Hyperlipidemia

Abstract

Hyperlipidemia is the fat particles excess in the serum. Hyperlipidemia increases the mortality rate that occurs with other metabolic disorders. Hyperlipidemia is classified into familial and acquired subgroups. Moreover, Hyperlipidemia etiology is based on environmental or genetic factors. For instance, abnormal HMG-CoA regulation down-regulates ubiquitin ligase and targets variable oxidative stress-related condition proteins. There has been proven reactive oxygen species (ROS) overshoot happens during hyperlipidemia occurrence. OS, directly and indirectly, regulates molecular cascades within the cell and leads to gene expression alteration. At this molecular juncture, AMPK is affected by ROS. AMPK is a serine-threonine kinase and a critical energy balance. Low energy conditions result in AMPK activation due to the down-regulation of protein and lipid synthesis. Furthermore, ER stress and activated unfolded protein proteasomal response and autophagy are AMPK mediated. Polyphenols are widespread dietary plant-based compounds that regulate gene expression and signal conduction. Through the hyperlipidemic state, FFAs releasing indirectly connect to AMPK/NF-κB pathway then polyphenols target them. AMPK, during this FFA exposure, down-regulates de novo lipid molecules generation. Likewise, if AMPK/mTOR pathway failure is prolonged, the hyperlipidemic state may be explicit, activated by natural herbal mediators, e.g., polyphenols. Polyphenols activate the AMPK signaling pathway and influence lipid metabolism. Polyphenol-mediated AMPK activation results in lipogenesis inhibition and lipophagy. Cholesterol efflux mediated polyphenols lipid-lowering effects, accessing LXR pathway. All these clues persist on direct or indirect AMPK-related polyphenolic anti-hyperlipidemic effects.

Short-Term Effects of PJE Administration on Metabolic Parameters in Diet-Induced Obesity Mice

“…Studies have shown that polyphenolics can modulate the composition and function of gut microbiota, which can help to improve metabolic parameters [ 45 , 48 ]. In addition to their effects on gut microbiota, polyphenolics can also directly modulate metabolic processes in various organs such as the liver, adipose tissue, and skeletal muscle [ 45 , 48 , 49 ], and have been found to activate AMP-activated protein kinase (AMPK), which is a key regulator of energy metabolism [ 50 , 51 ]. Activation of AMPK can help to increase glucose uptake and utilization, reduce lipid accumulation, and improve insulin sensitivity [ 51 , 52 ].…”

“…In addition to their effects on gut microbiota, polyphenolics can also directly modulate metabolic processes in various organs such as the liver, adipose tissue, and skeletal muscle [ 45 , 48 , 49 ], and have been found to activate AMP-activated protein kinase (AMPK), which is a key regulator of energy metabolism [ 50 , 51 ]. Activation of AMPK can help to increase glucose uptake and utilization, reduce lipid accumulation, and improve insulin sensitivity [ 51 , 52 ]. The bioavailability of polyphenolics is a crucial factor in determining their therapeutic potential.…”