Abstract
Intermittent fasting (IF) is a dietary intervention often used as an alternative to caloric restriction (CR) and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.
Highlights
Moderate reduction in ad libitum daily caloric intake without limiting essential and micronutrient access is a well-established mechanism to promote longer lifespans and/or healthier aging in a wide range of organisms, including humans [1, 2]
Restricted diets have been extensively shown to be related to changes in mitochondrial bioenergetics [2, 3, 26] which in turn are known to be determinant toward redox balance, since mitochondria are the most quantitatively relevant source of intracellular reactive oxygen species (ROS)
Since aging is often accompanied by increased oxidative tissue damage and loss of mitochondrial activity, many studies involving caloric restriction (CR) have focused on the bioenergetic and redox effects of this diet [4, 30], mostly showing that it decreased oxidative damage [5]
Summary
Moderate reduction in ad libitum daily caloric intake without limiting essential and micronutrient access (caloric restriction, CR) is a well-established mechanism to promote longer lifespans and/or healthier aging in a wide range of organisms, including humans [1, 2]. As an alternative to CR, some groups have proposed the use of intermittent fasting (IF), referred to as intermittent feeding or every other day feeding [6, 7], in which ad libitum feeding periods are alternated with fasting, avoiding the strict daily control of caloric intake In laboratory animals, this feeding protocol was first described by Carlson and Hoelzel, who observed a slight increment in rat life span [8]. IF has been shown to reduce obesity and have positive effects on some pathologies [11, 12] Despite some similarities such as promoting reduced body weight [13], substantial differences between CR and IF have been uncovered [5] and are, expected, since CR involves a daily reduction in food intake, while IF changes feeding frequency, and may not always result in a limitation of food ingestion [7, 14]. This study bridges this knowledge gap, and demonstrates that short-term IF affects redox balance in a tissueselective manner
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