Lifelong circadian and epigenetic drifts in metabolic syndrome

Epigenetic misprogramming during development is widely thought to have a persistent effect on the health of the offspring and may even be transmitted to the next generation. However, little is known about the stochastically, genetically and environmentally triggered epimutations occurring during an individual's lifetime. They may result from replication-dependent, replication-independent or DNA repair events. The rhythmic, circadian induction of a substantial proportion of genes by a network of clock genes, one of which is a histone acetyl transferase, nuclear receptors and transcription factors is controlled by chromatin remodeling. The associated circadian epigenetic patterns must be transient, sensitive to environmental cues and reversible. Links have been found between circadian rhythms and major components of energy homeostasis, thermogenesis and hunger-satiety, rest-activity rhythms and the sleep-wake cycle. Thus poorly adapted behavior or lifestyle and desynchronized cues may disturb the modulation of gene expression. This functional asynchrony may ultimately lead to persistence of aberrant and unphased "locking"or "leakage" of gene expression and inadapted responses in the body as a whole.