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AMPK regulates immunometabolism in sepsis
Jun Huang1, Ke Liu2, Shan Zhu3
1Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Hunan 410011, People's Republic of China.
Brain, Behavior, and Immunity
|November 8, 2017
Summary
AMP-activated protein kinase (AMPK) suppresses sepsis by regulating immune cell energy. AMPK deficiency boosts glycolysis and HMGB1 release, worsening sepsis, while its activation or PKM2 inhibition offers protection.
Area of Science:
- Immunometabolism
- Cellular Bioenergetics
- Critical Care Medicine
Background:
- Sepsis and septic shock are leading causes of mortality in intensive care units.
- Limited treatment options necessitate the identification of novel therapeutic targets.
- Understanding systemic inflammation and organ failure mechanisms is crucial.
Purpose of the Study:
- To investigate the role of AMP-activated protein kinase (AMPK) in sepsis.
- To identify key players in immune cell bioenergetic reprogramming during sepsis.
- To explore potential therapeutic targets for sepsis treatment.
Main Methods:
- Investigated AMPK's role in immune cell bioenergetic reprogramming.
- Utilized mouse models of endotoxic shock and polymicrobial sepsis.
- Administered AMPK activator (A-769662) and PKM2 inhibitor (shikonin).
Main Results:
- AMPK acts as a negative regulator of immune cell bioenergetics, suppressing sepsis.
- AMPK deficiency enhances pyruvate kinase isozyme M2 (PKM2)-dependent glycolysis, increasing HMGB1 release.
- AMPK activation protects against sepsis, while AMPK depletion or PKM2 inhibition exacerbates it.
Conclusions:
- AMPK is a critical regulator of immunometabolism in sepsis.
- Disruption of the AMPK-dependent pathway contributes to sepsis pathogenesis.
- Targeting the AMPK-immunometabolism axis offers a potential therapeutic strategy for sepsis.
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