Energy provisioning and inflammasome activation: The pivotal role of AMPK in sterile inflammation and associated metabolic disorders

Akhila H. Shrungeswara, Mazhuvancherry K. Unnikrishnan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)107-117
Number of pages11
JournalAnti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry
Issue number2
Publication statusPublished - 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology


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