Can brain neurons change identity? Lessons from obesity

It has long been thought that the functional identity of mammalian brain neurons is programmed during development and remains stable throughout adult life; however, certain populations of neurons continue to express active regulators of neuronal identity into adulthood. Prolonged exposure to diet-induced metabolic stress induces features of neuronal identity modification in adult mice, and maladaptive changes in neuronal identity maintenance have been linked to cognitive impairment in humans suffering from neurodegenerative diseases often associated with obesity. Here we discuss how, by unraveling the neurological roots of obesity, we may solve the puzzle of whether mammalian brain neurons retain identity plasticity into adulthood, while advancing knowledge of the pathogenic mechanisms at the interface of metabolic and neurodegenerative disorders.