AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases.
The adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism at the cellular as well as whole-body level. It is activated by low energy status that triggers a switch from ATP-consuming anabolic pathways to ATP-producing catabolic pathways. AMPK is involved in a wide range of biological activities that normalizes lipid, glucose, and energy imbalances. These pathways are dysregulated in patients with metabolic syndrome (MetS), which represents a clustering of major cardiovascular risk factors including diabetes, lipid abnormalities, and energy imbalances. Clearly, there is an unmet medical need to find a molecule to treat alarming number of patients with MetS. AMPK, with multifaceted activities in various tissues, has emerged as an attractive drug target to manage lipid and glucose abnormalities and maintain energy homeostasis. A number of AMPK activators have been tested in preclinical models, but many of them have yet to reach to the clinic. This review focuses on the structure-function and role of AMPK in lipid, carbohydrate, and energy metabolism. The mode of action of AMPK activators, mechanism of anti-inflammatory activities, and preclinical and clinical findings as well as future prospects of AMPK as a drug target in treating cardio-metabolic disease are discussed.
Esperion Therapeutics Inc., Plymouth, MI 48170, USA. ajitsriva@gmail.com
Rai Ajit K
RA
Srivastava
Stephen L
SL
Pinkosky
Sergey
S
Filippov
Jeffrey C
JC
Hanselman
Clay T
CT
Cramer
Roger S
RS
Newton
D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D050260:Carbohydrate Metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D020536:Enzyme Activators / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D050356:Lipid Metabolism
D020536:Enzyme Activators; D055372:AMP-Activated Protein Kinases