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Temporal partitioning of adaptive responses of the murine heart to fasting.

Abstract：

:Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function). Meal feeding benefits may be the result of daily periods of feeding and/or fasting, highlighting the need for improved understanding of the temporal adaptation of cardiometabolic tissues (e.g., heart) to fasting. Such studies may provide mechanistic insight regarding how time-of-day-dependent feeding/fasting cycles influence cardiac function. We hypothesized that fasting during the sleep period elicits beneficial adaptation of the heart at transcriptional, translational, and metabolic levels. To test this hypothesis, temporal adaptation was investigated in wild-type mice fasted for 24-h, or for either the 12-h light/sleep phase or the 12-h dark/awake phase. Fasting maximally induced fatty acid responsive genes (e.g., Pdk4) during the dark/active phase; transcriptional changes were mirrored at translational (e.g., PDK4) and metabolic flux (e.g., glucose/oleate oxidation) levels. Similarly, maximal repression of myocardial p-mTOR and protein synthesis rates occurred during the dark phase; both parameters remained elevated in the heart of fasted mice during the light phase. In contrast, markers of autophagy (e.g., LC3II) exhibited peak responses to fasting during the light phase. Collectively, these data show that responsiveness of the heart to fasting is temporally partitioned. Autophagy peaks during the light/sleep phase, while repression of glucose utilization and protein synthesis is maximized during the dark/active phase. We speculate that sleep phase fasting may benefit cardiac function through augmentation of protein/cellular constituent turnover.

journal_name

Life Sci

journal_title

Life sciences

authors

Brewer RA,Collins HE,Berry RD,Brahma MK,Tirado BA,Peliciari-Garcia RA,Stanley HL,Wende AR,Taegtmeyer H,Rajasekaran NS,Darley-Usmar V,Zhang J,Frank SJ,Chatham JC,Young ME

doi

10.1016/j.lfs.2018.01.031

subject

Has Abstract

pub_date

2018-03-15 00:00:00

pages

30-39

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(18)30043-2

journal_volume

197

pub_type

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Temporal partitioning of adaptive responses of the murine heart to fasting.