Abstracts
Résumé
L’épidémie mondiale de syndrome métabolique - défauts des métabolismes glucidique et lipidique, obésité abdominale, dyslipidémie et hypertension, risques d’obésité, de diabète de type 2 et de maladie cardiovasculaire - reflète la diversité des influences géoclimatiques et culturelles subies par les populations concernées et le caractère soudain des changements (alimentation pléthorique et/ou déséquilibrée, sédentarisation). Outre l’héritage progressif d’un « génotype économe », accumulé au cours de siècles ponctués par les famines, les individus des générations actuelles ont subi des altérations de leur programmation épigénétique, d’une part au cours de leur développement foetal et postnatal, en liaison avec une nutrition déséquilibrée et des désordres métaboliques maternels et, d’autre part, au cours de leur vie, en liaison avec leurs excès alimentaires et l’insuffisance de leur activité physique. Afin de convertir ce « phénotype économe », aujourd’hui devenu obsolète, en un « phénotype gaspilleur », il faut identifier les séquences concernées - gènes, soumis à empreinte ou non, ou transposons, procéder au décryptage des signaux épigénétiques en cause, de leur verrouillage ou de leur labilité, puis identifier ou concevoir des molécules (nutriments et médicaments) capables de prévenir (ou de modifier) un formatage épigénétique aberrant et inadapté.
Summary
The importance of epigenetic alterations has been acknowledged in cancer for about two decades by an increasing number of molecular oncologists who contributed to deciphering the epigenetic codes and machinery and opened the road for a new generation of drugs now in clinical trials. However, the relevance of epigenetics to common diseases such as metabolic syndrome and cardiovascular disease was less conspicuous. This review focuses on converging data supporting the hypothesis that, in addition to « thrifty genotype » inheritance, individuals with metabolic syndrome (MetS) - combining disturbances in glucose and insulin metabolism, excess of predominantly abdominally distributed weight, mild dyslipidemia and hypertension, with the subsequent development of obesity, type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) - have suffered improper « epigenetic programming » during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their lifetime. Moreover, as seen for obesity and T2D, MetS tends to appear earlier in childhood, to be more severe from generation to generation and to affect more pregnant women. Thus, in addition to maternal effects, MetS patients may display « transgenerational effects » via the incomplete erasure of epigenetic marks endured by their parents and grandparents. We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development throughout life. Increasing our understanding on epigenetic patterns significance and small molecules (nutrients, drugs) that reverse epigenetic (in)activation should provide us with the means to « unlock » silenced (enhanced) genes, and to « convert » the obsolete human thrifty genotype into a « squandering » phenotype.
Appendices
Références
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