Abstract
Caloric restriction (CR) has been demonstrated to prolong the life span of a variety of species. CR-induced reduction in core temperature (Tc) is considered a key mechanism responsible for prolonging life span in rodents; however, little is known about the regulation of CR-induced hypothermia as a function of the circadian cycle. We assessed how mild CR that resulted in a 10% reduction in body weight affected the 24 h patterns of Tc as well as heart rate (HR) and motor activity (MA) of the Brown Norway rat. Telemetered rats were allowed to feed for 20 weeks ad libitum (AL) or given a CR diet. Tc, HR, and MA of CR rats exhibited nocturnal reductions and diurnal elevations, opposite to that of AL rats. The effects of CR appeared to peak at ∼4 weeks. Metabolic rate (MR) and respiratory exchange ratio (RER) were measured overnight after 18 weeks of CR. MR and RER were elevated markedly at the time of feeding in CR rats and then declined during the night. We found that the pattern of Tc was altered with CR, characterized by elimination of high nocturnal Tc's typically observed in AL animals. In terms of mechanisms to prolong life span in CR animals, we suggest that the shift in the pattern of Tc during CR (i.e., elimination of high Tc's) may be as critical as the overall mean reduction in Tc. Future studies should address how the time of feeding may affect the thermoregulatory response in calorically restricted rats.
Highlights
Since the initial report by McCay and Crowell (1934) showing that underfed rats lived longer than rats fed ad libitum (AL), many studies have been performed revealing that caloric restriction (CR) without malnutrition increased both the maximum and mean life spans of laboratory rodents
We have shown that a relatively mild level of CR resulting in a 10% reduction in the ad lib body weight led to significant reductions in Tc, heart rate (HR), metabolic rate (MR), respiratory exchange ratio (RER), and elevation in motor activity (MA) in the Brown Norway rat
Application of radiotelemetry in unstressed and undisturbed animals showed that rats respond quickly to CR (~24 h) and show peak physiological responses after ~4 weeks of restriction
Summary
Since the initial report by McCay and Crowell (1934) showing that underfed rats lived longer than rats fed ad libitum (AL), many studies have been performed revealing that caloric restriction (CR) without malnutrition increased both the maximum and mean life spans of laboratory rodents. Aside from slowing aging, CR provides many health benefits. It delays or prevents many age-related diseases such as cardiovascular disease and cancer (Dirks and Leeuwenburgh 2006). CR involves a shift from state of growth and proliferation to maintenance and repair (Yu et al 1985) and is most effective when caloric intake of animals fed AL is reduced by 20–40% without malnutrition (Anderson et al 2009). Energy balance depends on the mechanisms that regulate and coordinate food intake and the different components of energy expenditure, including metabolic requirements for thermoregulation and physical activity. When food is in short supply, caloric intake is lower than energy expenditure, resulting in a negative energy balance (Hill et al 1985).
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