The effects of graded levels of calorie restriction: V. Impact of short term calorie and protein restriction on physical activity in the C57BL/6 mouse

Abstract

Calorie restriction (CR) delays the onset of age-related disease and extends lifespan in a number of species. When faced with reduced energy supply animals need to lower energy demands, which may be achieved in part by reducing physical activity (PA). We monitored changes in PA using implanted transmitters in male C57BL/6 mice in response to graded levels of CR (10 to 40%) or matched levels of graded protein restriction (PR) for 3 months. Mice were fed at lights out and ad libitum controls were limited to dark-phase feeding (12AL) or 24hr/day. Total daily PA declined in a non-linear manner over the first 30 days of CR or PR, remaining stable thereafter. Total daily PA was not related to the level of CR or PR. Total daily PA over the last 20 days of restriction was related to circulating leptin, insulin, tumor necrosis factor-α (TNF-α) and insulin-like growth factor (IGF)-1 levels, measured after 3 months. Mice under restriction showed a high level of activity in the 2hrs before feeding (food anticipatory activity: FAA). FAA followed a complex pattern, peaking around day 20, falling on ∼day 37 then increasing again. FAA was also positively related to the level of restriction and inversely to leptin, insulin, TNF-α and IGF-1. Non-FAA, in contrast, declined over the period of restriction, generally more so in mice under greater restriction, thereby offsetting to some extent the increase in FAA. Mice under PR displayed no changes in PA over time or in comparison to 12AL, and showed no increase in FAA.

Calorie restriction in rodents: Caveats to consider

“…We know now that this level of CR may be excessive for some strains of mice. The interaction between the degree of CR and different aspects of physiology has been recently examined (Derous et al, 2016a; Derous et al, 2016b; Lusseau et al, 2015; Mitchell et al, 2015a; Mitchell et al, 2016a; Mitchell et al, 2015b; Mitchell et al, 2015c) and survival (Mitchell et al, 2016b). …”

“…Efforts are now invested to further investigated this interplay between mouse strains, the level of restriction, and their impact on survival. The DBA results of Mitchell et al (2016) and those from John Speakman’s group in which the effects of different grades of CR in B6 mice elicit differential responses (Derous et al, 2016a; Derous et al, 2016b; Lusseau et al, 2015; Mitchell et al, 2015a; Mitchell et al, 2016a; Mitchell et al, 2015b; Mitchell et al, 2015c) open the door for new studies aimed at identify the underlying biological responses. Thus, one could predict that some of the recombinant inbred strains will have a beneficial response to CR if they were tested at a lower level of dietary restriction.…”

The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice

“…Additionally, we correlated these metabolites with physiological data (Mitchell et al, 2015a(Mitchell et al, ,c, 2016a. S1P and sphingomyelin were negatively correlated with body mass (S1P r = À0.761, P < 0.001 and SM Liver metabolomics of short-term calorie restriction, C. L. Green et al r = À0.453, P = 0.019) and positively correlated with food anticipatory activity (activity in the 2 h before food supply: FAA) (S1P r = 0.771, P < 0.001 and SM r = 0.365, P = 0.024), whereas ceramide correlated in the opposite direction (BM r = 0.550, P = 0.003 and FAA r = À0.412, P = 0.015).…”

The effects of graded levels of calorie restriction: VIII. Impact of short term calorie and protein restriction on basal metabolic rate in the C57BL/6 mouse

“…In some cases these responses have been compared to the equivalent responses to levels of protein restriction (PR) [14, 31, 35, 41]. Here we focus on BMR utilizing an essentially similar approach to that adopted by Selman et al (2005) [40].…”