Faculty Collaboration Database

Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice. J Neurochem 2011 Apr;117(1):154-63

Date

01/20/2011

Pubmed ID

21244426

Pubmed Central ID

PMC3055925

DOI

10.1111/j.1471-4159.2011.07184.x

Scopus ID

2-s2.0-79952570641 (requires institutional sign-in at Scopus site)   16 Citations

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.

Author List

Lu J, E L, Wang W, Frontera J, Zhu H, Wang WT, Lee P, Choi IY, Brooks WM, Burns JM, Aires D, Swerdlow RH

Author

Lezi E PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Animals
Blood Glucose
Brain
Energy Metabolism
Fasting
Insulin
Male
Mice
Mice, Inbred C57BL
Signal Transduction
Time Factors