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Alternate day fasting impacts the brain insulin‐signaling pathway of young adult male C57BL/6 mice
Author(s) -
Lu Jianghua,
E Lezi,
Wang WenFang,
Frontera Jennifer,
Zhu Hao,
Wang WenTung,
Lee Phil,
Choi In Young,
Brooks William M.,
Burns Jeffrey M.,
Aires Daniel,
Swerdlow Russell H.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07184.x
Subject(s) - mitochondrial biogenesis , endocrinology , medicine , insulin receptor , ketogenic diet , biology , insulin , bioenergetics , gsk 3 , protein kinase b , signal transduction , phosphorylation , glycogen , mitochondrion , insulin resistance , biochemistry , neuroscience , epilepsy
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.