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Energy Provisioning and Inflammasome Activation: The Pivotal Role of AMPK in Sterile Inflammation and Associated Metabolic Disorders

[ Vol. 20 , Issue. 2 ]

Author(s):

Akhila H. Shrungeswara and Mazhuvancherry K. Unnikrishnan*   Pages 107 - 117 ( 11 )

Abstract:


Background: Body defenses and metabolic processes probably co-evolved in such a way that rapid, energy-intensive acute inflammatory repair is functionally integrated with energy allocation in a starvation/ infection / injury-prone primitive environment. Disruptive metabolic surplus, aggravated by sedentary lifestyle induces chronic under-activation of AMPK, the master regulator of intracellular energy homeostasis. Sudden increase in chronic, dysregulated ‘sterile’ inflammatory disorders probably results from a shift towards calorie rich, sanitized, cushioned, injury/ infection free environment, repositioning inflammatory repair pathways towards chronic, non-microbial, ‘sterile’, ‘low grade’, and ‘parainflammation’. AMPK, (at the helm of energy provisioning) supervises the metabolic regulation of inflammasome activation, a common denominator in lifestyle disorders.

Discussion: In this review, we discuss various pathways linking AMPK under-activation and inflammasome activation. AMPK under-activation, the possible norm in energy-rich sedentary lifestyle, could be the central agency that stimulates inflammasome activation by multiple pathways such as 1: decreasing autophagy, and accumulation of intracellular DAMPs, (particulate crystalline molecules, advanced glycation end-products, oxidized lipids, etc.) 2: stimulating a glycolytic shift (pro-inflammatory) in metabolism, 3: promoting NF-kB activation and decreasing Nrf2 activation, 4: increasing reactive oxygen species (ROS) formation, Unfolded Protein Response (UPR) and Endoplasmic Reticulum (ER) stress.

Conclusion: The ‘inverse energy crisis’ associated with calorie-rich, sedentary lifestyle, advocates dietary and pharmacological interventions for treating chronic metabolic disorders by overcoming / reversing AMPK under-activation.

Keywords:

Inflammasome, AMPK, inflammation, metabolic disorders, inflammatory signals, sterile.

Affiliation:

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, Department of Pharmacology, National College of Pharmacy, Kerala University of Health Sciences, Kozhikode

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