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Identifier 000423677
Title Επίδραση μεταβολικών παραγόντων στην ενεργοποίηση και απενεργοποίηση των μακροφάγων / Ελευθερία Ιερωνυμάκη.
Alternative Title Effect of metabolic factors on macrophage activation and inactivation
Author Ιερωνυμάκη, Ελευθερία
Thesis advisor Τσατσάνης, Χρήστος
Reviewer Ηλιόπουλος, Αριστείδης
Χαμηλός, Γεώργιος
Καρδάσης, Δημήτριος
Βενυχάκη, Μαρία
Μπερτσιάς, Γεώργιος
Φιλιππάτος, Θεοδόσιος
Abstract Obesity constitutes an important risk factor for the development of metabolic syndrome and a variety of other obesity-related pathologic conditions. Obesity induces a chronic low grade metabolic inflammation. Macrophages are important mediators of inflammatory responses and metabolic factors directly act on their function. They can be polarized either towards a pro-inflammatory, M1 phenotype or an anti-inflammatory, M2 phenotype depending on their environmental stimuli. In the present study we investigated the effect of insulin resistance on macrophage activitηνλ. For this purpose we employed macrophages that acquired insulin resistance, being macrophages exposed to high insulin concentrations either in vitro or in vivo in a mouse model of high-fat diet induced insulin resistance, as well as macrophages that lack Akt2 isoform or Insulin-like growth factor 1 receptor (Igf1R). These macrophages showed impaired insulin signaling, while the Akt1/mTORC1 pathway was activated at the basal levels. Insulin resistant macrophages obtained an M2-like phenotype, termed M-InsR, and displayed a metabolic shift towards glycolysis Subsequently, in order to investigate the contribution of insulin resistant macrophages in acute inflammatory responses, an in vivo model of polymicrobial sepsis in wild type, diet-induced obese, Akt2-/- and LysMCreIgf1Rfl/fl mice. We found that both inflammation and lung injury were significantly milder in mice harboring insulin resistant macrophages. Finally, M-InsR macrophages have an important role in sustained inflammatory responses, since they can shape microbial composition of the gut irrespective of the diet. This study describes a kind of innate immune memory in peripheral macrophages characterized by an M2-like phenotype, which is under the control of Akt1/mTORC1 signals and glycolytic metabolism. This phenotype may explain the changes in macrophage responses and development of related pathologic conditions that occur in obesity.
Language English
Subject Insulin resistance
Αντίσταση στην ινσουλίνη
Issue date 2019-07-17
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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