[Nutritional epigenomics of metabolic syndrome].
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 programing" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their life-time. 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 he obsolete human thrifty genotype into a "squandering" phenotype.
Junien
Claudine
C
Inserm U.383, Génétique, chromosome et cancer, Hôpital Necker Enfants-Malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France. junien@necker.fr
Gallou-Kabani
Catherine
C
Vigé
Alexandre
A
Gross
Marie-Sylvie
MS
D000818:Animals; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D023281:Genomics; D006801:Humans; D007225:Infant Food; D007231:Infant, Newborn; D024821:Metabolic Syndrome / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D009747:Nutritional Physiological Phenomena / Q000502:physiology*; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy