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. 2015 Jul 30;6(21):18314-37.
doi: 10.18632/oncotarget.4506.

The Effects of Graded Levels of Calorie Restriction: III. Impact of Short Term Calorie and Protein Restriction on Mean Daily Body Temperature and Torpor Use in the C57BL/6 Mouse

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Free PMC article

The Effects of Graded Levels of Calorie Restriction: III. Impact of Short Term Calorie and Protein Restriction on Mean Daily Body Temperature and Torpor Use in the C57BL/6 Mouse

Sharon E Mitchell et al. Oncotarget. .
Free PMC article

Abstract

A commonly observed response in mammals to calorie restriction (CR) is reduced body temperature (Tb). We explored how the Tb of male C57BL/6 mice responded to graded CR (10 to 40%), compared to the response to equivalent levels of protein restriction (PR) over 3 months. Under CR there was a dynamic change in daily Tb over the first 30-35 days, which stabilized thereafter until day 70 after which a further decline was noted. The time to reach stability was dependent on restriction level. Body mass negatively correlated with Tb under ad libitum feeding and positively correlated under CR. The average Tb over the last 20 days was significantly related to the levels of body fat, structural tissue, leptin and insulin-like growth factor-1. Some mice, particularly those under higher levels of CR, showed periods of daily torpor later in the restriction period. None of the changes in Tb under CR were recapitulated by equivalent levels of PR. We conclude that changes in Tb under CR are a response only to the shortfall in calorie intake. The linear relationship between average Tb and the level of restriction supports the idea that Tb changes are an integral aspect of the lifespan effect.

Keywords: Gerotarget; body temperature; calorie restriction; dietary restriction; protein restriction; torpor.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Mean daily body temperatures of the two ad libitum (AL) fed groups throughout the experiment
The animals with 24 hour AL food access (24AL) are shown as open symbols and the mice with 12 hour AL food access (12AL) are shown as closed symbols. The x-axis is the day of treatment with Day is the start of ‘calorie restriction’. Prior to that (negative days) all mice were at baseline and fed only during the 12 hrs of darkness. (n = 7 in the 24AL and 8 in the 12AL groups). The grey line shows fitted regression over days 0 to 83 for 24AL animals and the black line fitted regression for 12AL animals over the same period. Results are expressed as mean ± SD.
Figure 2
Figure 2. Mean daily body temperatures of the graded calorie restriction (CR) and protein restriction (PR) groups throughout the experiment
a. The four CR groups, 10%, 20%, 30% and 40% restriction are labelled 10CR, 20CR, 30CR and 40CR respectively, along with the 12AL group fed ad libitum in 12 hrs of darkness. The 24AL group is omitted for clarity. b. The three PR groups, labelled 20PR, 30PR and 40PR, matched levels of protein for 20CR, 30CR and 40CR without a reduction in calories. The x-axis is the day of restriction with Day 0 the start of ‘calorie restriction’. Prior to that (negative days) all mice were at baseline and fed only during the 12 hrs of darkness. (n = 6 to 8 individuals per group). Note the different body temperature axis on this plot compared with Figure 1. Results are expressed as mean ± SD.
Figure 3
Figure 3. The response of mean daily body temperature to calorie restriction (CR)
a. the time taken for the mean daily body temperature curve to inflect following the onset of restriction, calculated from the fitted polynomial regression curves (for curve parameters refer to Table 1), in relation to the level of restriction (10, 20, 30 and 40% CR) (n = 6 to 8 individuals per group). b. the average level of mean daily body temperature across all individuals between days 35 and 70 when the level was relatively stable.
Figure 4
Figure 4. The relationship between body mass (BM) and mean daily body temperature throughout the entire experiment
Individuals in each group are coded with a different symbol. 24AL and 12AL fed ad libitum for 24 and 12 hrs respectively a & b. The 4 treatment groups were restricted by 10, 20, 30, 40% referred to as 10CR, 20CR, 30CR and 40CR respectively c–f. In all groups there was a significant effect of BM on mean body temperature, a random effect of individual, and also an individual by mass interaction (for detailed statistics refer to Table 2). In the AL fed groups BM was negatively related to body temperature and in the CR fed animals it was positively related to body temperature.
Figure 5
Figure 5. The relationship between mean daily body temperature and body mass (BM)
Data was pooled data across all individuals in all treatment groups (n = 4126). Individuals are coded with different symbols. There appeared to be a pivotal BM of 27g above which mass had a negative effect on body temperature and below which the effect was positive.
Figure 6
Figure 6. The relationship between mean daily body temperature (Tb) measured over the last 20 days of the experiment and body composition
Tb was averaged over days 65–84 and plotted against the body composition of the animals at dissection (day 84). Data on body composition are from [43]. a. the effect of total body fat (pooled masses of sub-cutaneous, epididymal, retroperitoneal and mesenteric fat depots). b. the effect of total structural tissue (pooled carcass, skin and tail masses). (Please see text for statistical details).
Figure 7
Figure 7. The relationship between mean daily body temperature (Tb) measured over the last 20 days of the experiment and hormone levels
Tb was averaged over the last 20 days 65–84 and plotted against circulating hormone levels measured at dissection (day 84). Data on hormone levels were previously reported [44]. a. leptin b. insulin, c. tumor necrosis factor alpha (TNF-α) and d. insulin like growth factor 1 (IGF-1). In all cases there were significant effects (see text for statistical details).
Figure 8
Figure 8. Body temperature fluctuations over a 24 hr period at varying timepoints over 12 weeks of calorie restriction (CR)
a. baseline, b. 1 week of CR c. 4 weeks of CR and d. at the end of study following 11 weeks of CR. The period of darkness is shown by black bars along the x-axis. CR mice were fed at lights out. 24AL and 12AL represent animals fed ad libitum for 24 and 12 hrs respectively. The 4 treatment groups restricted by 10, 20, 30, 40% are referred to as 10CR, 20CR, 30CR and 40CR respectively. Data is presented as mean ± SD.
Figure 9
Figure 9. Torpor use during calorie restriction (CR)
a. the proportion of animal-days when torpor was reported within the 3 treatment groups displaying torpor (10CR, 30CR and 40CR. The x-axis shows the time course of the experiment split into 5 day periods. b. The probability of an individual animal showing torpor in relation to body mass, calculated across all 4126 animal-days.
Figure 10
Figure 10. The effect of body composition on the propensity of individual animals to display torpor
a. body fat and b. structural tissue. The maximum possible number of torpor days during the experiment was 84. Different groups are shown with different symbols.
Figure 11
Figure 11. Body temperature during torpid and non-torpid bouts
a. the average body temperature during torpor bouts in relation to the day of restriction for mice under 30% calorie restriction (30CR) (closed symbols) and 40CR (open symbols). Mice went into deeper torpor when exposed to 40CR compared to 30CR and torpor temperature declined as the experiment proceeded. b. non-torpid body temperature over the last 20 days of the manipulation (days 65 to 84) calculated as the temperature averaged across hourly periods when the body temperature was greater than 31°C. Data are presented as mean ± SD.
Figure 12
Figure 12. Body temperature fluctuations over a 24 hr period at varying timepoints over 12 weeks of graded protein restriction (PR) throughout the experiment
Body temperatures were measured in the three restricted protein intake groups (20%, 30% and 40% restriction labelled 20PR, 30PR and 40PR respectively) along with the control group fed 12 hrs ad libitum (12AL) at a. baseline, b. 1 week, c. 4 week and d. 11 weeks of study. The x-axis is the day of measurement. Day 0 is the start of PR. Prior to that (negative days) all mice were at baseline and fed only during the 12 hours of darkness. (n = 8 individuals per group). Data is presented as mean ± SD.
Figure 13
Figure 13. Comparisons of the body temperature responses to caloric restriction (CR) and protein restriction (PR)
a. the two control ad libitum fed groups (12AL) that were both fed the same diet (20% protein) available only during the hours of darkness. b, c. and d. show the mice under respectively 20, 30 and 40% CR matched to mice under 20, 30 and 40% PR. All plots are presented on a common scale. The x-axis is the day of measurement. Day 0 is the start of restriction. Prior to that (negative days) all mice were at baseline and fed only during the 12 hours of darkness. (n = 8 individuals per group except in 30CR where n = 6). Data is presented as mean ± SD.
Figure 14
Figure 14. A hypothetical model for the interplay of body composition and body temperature in response to caloric restriction (CR)
For further explanation refer to the text.

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