Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.
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.
Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Jianghua
J
Lu
Lezi
L
E
Wenfang
W
Wang
Jennifer
J
Frontera
Hao
H
Zhu
Wen-Tung
WT
Wang
Phil
P
Lee
In Young
IY
Choi
William M
WM
Brooks
Jeffrey M
JM
Burns
Daniel
D
Aires
Russell H
RH
Swerdlow
D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005215:Fasting / Q000378:metabolism*; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin
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