Emerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver

Abstract

This review summarizes the emerging role of AMP-activated protein kinase (AMPK) in mediating endocrine regulation of metabolic fluxes in the liver. There are a number of hormones which, when acting on the liver, alter AMPK activation. Here we describe those hormones associated with activation and de-activation of AMPK and the potential mechanisms for changes in AMPK activation state. The actions of these hormones, in many cases, are consistent with downstream effects of AMPK signaling thus strengthening the circumstantial case for AMPK-mediated hormone action. In recent years, genetic mouse models have also been used in an attempt to establish the role of AMPK in hormone-stimulated metabolism in the liver. Few experiments have, however, firmly established a causal relationship between hormone action at the liver and AMPK signaling.

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

“…Third, inducing GNG reduces energy charge, activates AMPK, and increases oxidative metabolism. When PEPCK was absent, the AMPK response was negated (47). Consistent with this mechanism, knockdown mice had elevated energy charge.…”

Imidazoline-like drugs improve insulin sensitivity through peripheral stimulation of adiponectin and AMPK pathways in a rat model of glucose intolerance

“…Adiponectin, through AMPK-dependent transduction pathways, is a well-established insulin sensitizer (20,21,45). In hepatocytes, AMPK phosphorylation could attenuate insulin resistance acting at lipid and/or glucose homeostasis by 1) decreasing triglycerides synthesis, 2) inhibiting hepatic gluconeogenesis following modifications of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and 3) increasing fatty acid oxidation, mitochondrial biogenesis, and glucose transport (4,25,34).…”

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) Effect on Glucose Production, but Not Energy Metabolism, Is Independent of Hepatic AMPK in Vivo

“…The elevation in plasma lactate, however, was partially attenuated in ␣1␣2 lox/lox ϩ Albcre mice (Table 2). AMPK activation during energy stress is implicated in fat utilization in the liver (15). Liver TG levels in ␣1␣2 lox/lox and ␣1␣2 lox/lox ϩ Albcre mice at the end of the saline infusion were not statistically different (24.6 Ϯ 0.8 and 29.1 Ϯ 2.0 mg/g of liver) ( Table 2).…”

“…Evidence supports a role for AMPK in regulating fat utilization and mitochondrial function in the liver (15)(16)(17). Furthermore, AICAR (18 -20) and metformin (18,21) promote hepatic fat utilization and suppress lipogenic signaling.…”