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Metabolic adaptation to cell growth and proliferation in normal and pathological conditions

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In western countries, a 60% of the mortality rate is caused by few pathological conditions such obesity, diabetes and cancer. A common hallmark of these pathologies is an impaired energy balance due to abnormal metabolic flexibility. Metabolic adaptation is key to ensure a coordinated cellular response to ...

In western countries, a 60% of the mortality rate is caused by few pathological conditions such obesity, diabetes and cancer. A common hallmark of these pathologies is an impaired energy balance due to abnormal metabolic flexibility. Metabolic adaptation is key to ensure a coordinated cellular response to physiological and pathological conditions, being the cellular context and nutrient availability two critical determinants for this response. Cell proliferation, growth and metabolism are tightly linked processes, as proliferative or differentiated tissues display clearly distinct metabolic profiles. In tissues with high proliferative rates, nutrient availability engages synthetic pathways of biological blocks required for proliferation and growth. In contrast, nutrient deprivation promotes a metabolic switch that restricts cell proliferation to favor energy production. Remarkably, non-proliferative cells from differentiated tissues behave in the opposite way: as proliferation is no longer a demand, catabolic pathways are predominantly used to sustain energetic needs. Several physiological conditions are characterized by major changes in the cellular metabolism, i.e., development, regeneration, exercise or the immune response. In a pathological context, evidence for a metabolic reorganization occurring in several conditions (diabetes, obesity and cancer) has emerged during the last decades. Therefore, dissecting the links between cell proliferation and metabolism will permit to better target such metabolic changes and thus open new opportunities for therapeutic treatment.


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