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2017 ; 8
(ä): 352
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Thermodynamics in Gliomas: Interactions between the Canonical WNT/Beta-Catenin
Pathway and PPAR Gamma
#MMPMID28620312
Vallée A
; Lecarpentier Y
; Guillevin R
; Vallée JN
Front Physiol
2017[]; 8
(ä): 352
PMID28620312
show ga
Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities
with an increasing entropy rate which is characteristic of irreversible processes
driven by changes in Gibbs energy, heat production, intracellular acidity,
membrane potential gradient, and ionic conductance. We focus our review on the
opposing interactions observed in glioma between the canonical WNT/beta-catenin
pathway and PPAR gamma and their metabolic and thermodynamic implications. In
gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is
downregulated. Upregulation of WNT/beta-catenin signaling induces changes in key
metabolic enzyme that modify their thermodynamics behavior. This leads to
activation pyruvate dehydrogenase kinase 1(PDK-1) and monocarboxylate lactate
transporter 1 (MCT-1). Consequently, phosphorylation of PDK-1 inhibits pyruvate
dehydrogenase complex (PDH). Thus, a large part of pyruvate cannot be converted
into acetyl-CoA in mitochondria and in TCA (tricarboxylic acid) cycle. This leads
to aerobic glycolysis despite the availability of oxygen, named Warburg effect.
Cytoplasmic pyruvate is, in major part, converted into lactate. The
WNT/beta-catenin pathway induces also the transcription of genes involved in cell
proliferation, cell invasiveness, nucleotide synthesis, tumor growth, and
angiogenesis, such as c-Myc, cyclin D1, PDK. In addition, in gliomas cells, PPAR
gamma is downregulated, leading to a decrease in insulin sensitivity and an
increase in neuroinflammation. Moreover, PPAR gamma contributes to regulate some
key circadian genes. Abnormalities in the regulation of circadian rhythms and
dysregulation in circadian clock genes are observed in gliomas. Circadian rhythms
are dissipative structures, which play a key role in far-from-equilibrium
thermodynamics through their interactions with WNT/beta-catenin pathway and PPAR
gamma. In gliomas, metabolism, thermodynamics, and circadian rhythms are tightly
interrelated.