AMPK-Dependent Metabolic Regulation by PPAR Agonists

Abstract

Comprehensive studies support the notion that the peroxisome proliferator-activated receptors, (PPARs), PPARα, PPARβ/δ, and PPARγ, regulate cell growth, morphogenesis, differentiation, and homeostasis. Agonists of each PPAR subtype exert their effects similarly or distinctly in different tissues such as liver, muscle, fat, and vessels. It is noteworthy that PPARα or PPARγ agonists have pharmacological effects by modulating the activity of AMPK, which is a key cellular energy sensor. However, the role of AMPK in the metabolic effects of PPAR agonists has not been thoroughly focused. Moreover, AMPK activation by PPAR agonists seems to be independent of the receptor activation. This intriguing action of PPAR agonists may account in part for the mechanistic basis of the therapeutics in the treatment of metabolic disease. In this paper, the effects of PPAR agonists on metabolic functions were summarized with particular reference to their AMPK activity regulation.

The Med1 Subunit of the Mediator Complex Induces Liver Cell Proliferation and Is Phosphorylated by AMP Kinase

“…5). PPAR␣ activators fenofibrate and Wy-14,643 activate the AMPK signaling pathway (53,54,70,71). We reported here the attenuation of hepatocyte proliferation in the liver of wild-type mice by compound C; they were fed a diet containing the PPAR␣ activator Wy-14,643, suggesting that AMPK is also involved in the PPAR␣ pathway.…”

Effects of metformin on middle cerebral artery flow velocity in newly diagnosed type 2 Diabetic patients

“…Moreover, metformin decreases β-cells apoptosis and slows diabetes disease progression [37][38][39]. Many of these effects are mediated through AMP-kinase pathway [22,23,30]. Nowadays, metformin use is recommended in the onset of diabetes type 2 [17].…”

“…Fourth: metformin may increase endothelial NO via AMPK activation pathway. Recent studies demonstrated that metformin increases the bioavailability of nitric oxide and eNOS through activation of AMPK pathway [22]. Furthermore, AMPK pathway activation increases the activity of peroxisome proliferator activated receptor gamma which is a transcription factor increases lipid oxidation and utilization in skeletal muscles as well as has important role in regulation of glucose metabolism [23].…”

Effect of L-carnitine administration on serum insulin and adiponectin levels, and AMPK, APPL1 and PPAR? gene expression in STZ-induced diabetic rat liver

“…Also, TZDs which are strong insulin sensitizers' drugs, act via PPARγ agonism [13,14]. Besides TZDs ben ficial effects in diabetes there are some deteriorating effects following TZDs administration which include hepatotoxicity and hepatic failure [25].…”

“…Anti-diabetic drugs, thiazolidinediones (TZDs), activate peroxisome proliferator-activated receptor-gamma (PPARγ) and consequently increase insulin sensitivity. PPARγ activation promotes insulin sensitivity and improves insulin receptor signaling in diabetes [13,14]. TZDs may affect insulin sensitivity by AMPK activation [12].…”