Over 70 years ago, a team of scientists discovered that a reduction of daily caloric intake can prolong lifespan in rats. Since then, a moderate caloric restriction has been associated with increased longevity in a variety of organisms ranging from yeast to mice. Animals subjected to caloric restriction typically exhibit reduced occurrence of age-related disorders such as cardiovascular diseases, diabetes and oxidative damage, resulting in an overall longer life expectancy. Although the exact mechanisms promoting these health benefits remain elusive, it has been argued that caloric restriction could reduce oxidative stress in cells, therefore preventing excessive oxidative damage. Furthermore, when carbohydrates are oxidized in the mitochondria they tend to produce more oxidative stress than lipids, so it has been further hypothesized that an increased reliance on fatty acids vs carbohydrates could mediate the health benefits of caloric restriction. However, the nutrient composition of the caloric restriction diet is similar to that of a regular diet; that is, the two diets have the same relative lipid content. Therefore, this hypothesis cannot hold unless calorie-restricted animals are synthesizing more lipids than their satiated counterparts. In this study, Matthew Bruss and his colleagues from the University of California at Berkeley and the Children's Hospital in Oakland (USA) sought to test this hypothesis by examining fuel selection patterns in calorie-restricted mice.
The team reduced the caloric intake of mice by 30% and measured their oxygen consumption and CO2 production to examine their fuel preferences over several weeks. The authors initially discovered that the calorie-restricted mice wolfed down their entire daily food ration within an hour of the food arriving and essentially fasted for the next 23 h. Monitoring the fuel sources that the animals used while fasting, the team found that during the first 6 h after being fed, the mice used carbohydrates for their energetic needs and synthesized their own fatty acids. During the rest of the day, the rodents relied almost exclusively on lipids as metabolic fuels, burning four times more lipids than if they were on a normal diet, and three times more than their actual daily fat intake.
As these results strongly suggested that calorie-restricted mice synthesized more lipids, Bruss and his colleagues further examined changes in the animals' lipid production. The team confirmed that calorie-restricted mice exhibited elevated rates of lipid synthesis and retention. Furthermore, they found that shortly after their meal the mice started producing and storing the majority of these lipids in their adipose tissues.
Using classical physiological techniques, Bruss and colleagues elegantly demonstrated unique metabolic adjustments in calorie-restricted mice. The team clearly showed that the calorie-restricted mice switched to a predominant reliance on their own newly synthesized fatty acids as oxidative fuels and there was a pattern to the timing of this shift, which should most definitely be kept in mind for future experimental designs. The next logical step is probably to ask the question: is burning more fat the key to living a long, healthy, calorie-restricted life?