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Search command : Author="Κάραλη"
And Author="Αικατερίνη"
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| Identifier |
000416897 |
| Title |
The role of immune system in the diet -induced non-alcoholic fatty liver disease |
| Alternative Title |
Ο ρόλος του ανοσοποιητικού συστήματος στη διατροφικής αιτιολογία λιπώδη διήθηση του ύπατος |
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Author
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Μωυσίδου, Μαρία
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Thesis advisor
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Βενυχάκη, Μαρία
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Reviewer
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Κάραλη, Αικατερίνη
Μαργιωρής, Ανδρέας
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| Abstract |
Accumulation of lymphocytes in the white adipose tissue (WAT) in obesity is linked to insulin resistance and the associated chronic inflammatory state, whereas the role of this cell population in the coordinated regulation of the overall energy homeostasis remains unclear. Here, we demonstrate enhanced energy dissipation in Rag1-/- mice that was “normalized” to the levels detected in the WT mice by adoptive transfer of lymphocytes. Recapitulation of this effect by CD8+ T cells alone provided evidence that the CD8+ T cell deficiency of the Rag1-/- mice is the primary reason behind their enhanced energy utilization reflected primarily to their profoundly increased beige fat depot within the subcutaneous white adipose tissue (scWAT). Consistently, CD8-/- mice also presented with enhanced beige adipogenesis. The reversal of beige adipogenesis in the Rag1-/- mice reconstituted with CD8+ T cells was inhibited by blockade of IFNγ, a main secretory product of the CD8+ T cells in the adipose tissue. Our findings identify a novel effect of CD8+ T cells in regulating energy dissipation in lean WAT, mediated by IFNγ and the significant modulation of the abundance of resident innate immune cells and of the catecholaminergic activity within the scWAT. We also demonstrate that similar mechanisms operate in the liver of Rag1-/- mice to confer protection from lipid storage and development of steatosis in states of wasting due to altered caloric intake such as starvation. These findings provide a plausible explanation for the metabolic dysfunction in patients with diseases characterized by altered CD8+ T cell numbers, such as chronic parasitoses, or states associated with cachexia. Overall we demonstrate the effects of CD8+ T cells in energy homeostasis via regulation of lipid metabolism in the WAT and the liver. These data suggest that targeting of CD8+ T cells may provide a promising therapeutic approach in humans with obesity and other diseases associated with profoundly altered energy homeostasis.
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| Language |
English |
| Subject |
Energy homeostasis |
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Ενεργειακή ομοιόσταση |
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Λιπώδης ιστός |
| Issue date |
2018-07-18 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/d/6/8/metadata-dlib-1535986303-913507-22488.tkl
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| Views |
327 |
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