Dietary restriction alters insulin signaling pathway in the brain

Insulin is known to be a key hormone in the regulation of peripheral glucose homeostasis, but beyond that, its effects on the brain are now undisputed. Impairments in insulin signaling in the brain, including changes in insulin levels, are thought to contribute significantly to declines in cognitive performance, especially during aging. As one of the most widely studied experimental interventions, dietary restriction (DR) is considered to delay the neurodegenerative processes associated with aging. Recently, however, data began to suggest that the onset and duration of a restrictive diet play a critical role in the putative beneficial outcome. Because the effects of DR on insulin signaling in the brain have been poorly studied, we decided to examine the effects of DR that differed in onset and duration: long-term DR (LTDR), medium-term DR (MTDR), and short-term DR (STDR) on the expression of proteins involved in insulin signaling in the hippocampus of 18- and 24-month-old male Wistar rats. We found that DR-induced changes in insulin levels in the brain may be independent of what happens in the periphery after restricted feeding. Significantly changed insulin content in the hippocampus, together with altered insulin signaling were found under the influence of DR, but the outcome was highly dependent on the onset and duration of DR.