Alternate day fasting impacts the brain insulin‐signaling pathway of young adult male C57BL/6 mice

Abstract

J. Neurochem. (2011) 117, 154–163. Abstract Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics‐relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five‐month‐old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24‐h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin‐signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator‐activated receptor‐gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production.

Relationships Between Mitochondria and Neuroinflammation: Implications for Alzheimer's Disease

“…Hypoglycemia did not occur on the fasting day and we hypothesize this was due to liver gluconeogenesis. However, in the brains of the alternate day fasted mice we nevertheless observed evidence of reduced insulin signaling pathway activity, which presumably reflected reduced peripheral insulin production [56]. …”

Potentiation of dietary restriction-induced lifespan extension by polyphenols

“…We previously reported that the addition of this PAO combination to this IF DR protocol did not alter insulin sensitivity or glucose tolerance in male C57BL/6 mice [19]. We now report addition of PAO to the IF protocol did not affect the weight of the mice.…”

Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age

“…Recent clinical investigations have documented the benefits of short-term IF in both obese (Varady et al 2009;Varady 2011) and normal-weight human subjects (Heilbronn et al 2005;Varady and Hellerstein 2007;Trepanowski et al 2011). However, the effect of IF on blood glucose regulatory dynamics in mice has been rarely assessed (Anson et al 2003;Arum et al 2009;Lu et al 2011). Considering the validated adherence and easy modifiability of IF regimens for clinical intervention, studies into the outcomes of IF upon middle-aged or older subjects are very important for addressing the aging-associated declines in blood glucose control in a graying population (Kinsella and Wan 2009).…”