The effects of graded levels of calorie restriction: IV. Non-linear change in behavioural phenotype of mice in response to short-term calorie restriction

Abstract

Animals have to adjust their activities when faced with caloric restriction (CR) to deal with reduced energy intake. If CR is pronounced, allostasis can push individuals into alternate physiological states which can result in important health benefits across a wide range of taxa. Here we developed a new approach to determine the changes in behavioural phenotype associated with different levels of CR. We exposed C57BL/6 male mice to graded CR (from 0 to 40%) for three months and defined their behavioural phenotype using hidden Markov models of their movement and body temperature. All 40% CR mice exhibited a state-shift in behavioural phenotype and only some exposed to 30% CR did. We show for the first time that mice changed their activity characteristics rather than changed their activities. This new phenotyping approach provides an avenue to determine the mechanisms linking CR to healthspan.

Costs of exploratory behavior: the energy trade-off hypothesis and the allocation model tested under caloric restriction

“…Specifically, our results show an inverse relation between temperature variables (i.e., liver catabolism, skin temperature) and locomotor activity (i.e., percentage www.nature.com/scientificreports www.nature.com/scientificreports/ of activity time). Similar results have been found in multiple studies that address food stochasticity and caloric restriction in rodents 16,[48][49][50][51][52][53][54][55] . This reduction of temperature is possible, since rodents are a group of homeotherms capable of lowering their body temperature below 31 °C 15 and even prefer colder temperatures than their thermoneutral zones 56 .…”

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.…”

A predictive model of rats’ calorie intake as a function of diet energy density

“…These variables have been reported in various studies as the major factors that affect the food intake of rodents. For instance, in a recent study, the set of the main covariates of food intake that were considered for modeling the effects of calorie restriction on the behavioral phenotype of a group of mice included several variations of the time elapsed from the beginning of each diet change and body weight of animals (21).…”

“…Developing models that can describe food intake patterns in animals (without including the connection to the rewarding aspects) has been the subject of many works. For instance, Lusseau et al presented a mathematical model for describing the food intake patterns of mice that undergo calorie restrictions using a Markov model by setting the probabilities of transition between the states of the Markov model (representing shifting across different physiological states) (21). In addition to modeling food intake patterns, other studies have presented mathematical models for studying energy metabolism in animals (3,9,18).…”