Dataset Information

Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction.

ABSTRACT: Chronic caloric restriction (CR) without malnutrition is known to affect different cellular processes such as stem cell function, cell senescence, inflammation, and metabolism. Despite the differences in the implementation of CR, the reduction of calories produces a widespread beneficial effect in noncommunicable chronic diseases, which can be explained by improvements in immuno-metabolic adaptation. Cellular adaptation that occurs in response to dietary patterns can be explained by alterations in epigenetic mechanisms such as DNA methylation, histone modifications, and microRNA. In this review, we define these modifications and systematically summarize the current evidence related to CR and the epigenome. We then explain the significance of genome-wide epigenetic modifications in the context of disease development. Although substantial evidence exists for the widespread effect of CR on longevity, there is no consensus regarding the epigenetic regulations of the underlying cellular mechanisms that lead to improved health. We provide compelling evidence that CR produces long-lasting epigenetic effects that mediate expression of genes related to immuno-metabolic processes. Epigenetic reprogramming of the underlying chronic low-grade inflammation by CR can lead to immuno-metabolic adaptations that enhance quality of life, extend lifespan, and delay chronic disease onset.

SUBMITTER: Hernandez-Saavedra D

PROVIDER: S-EPMC6520046 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction.

Hernández-Saavedra Diego D Moody Laura L Xu Guanying Bianca GB Chen Hong H Pan Yuan-Xiang YX

Advances in nutrition (Bethesda, Md.) 20190501 3

Chronic caloric restriction (CR) without malnutrition is known to affect different cellular processes such as stem cell function, cell senescence, inflammation, and metabolism. Despite the differences in the implementation of CR, the reduction of calories produces a widespread beneficial effect in noncommunicable chronic diseases, which can be explained by improvements in immuno-metabolic adaptation. Cellular adaptation that occurs in response to dietary patterns can be explained by alterations ...[more]

PMID: 30915465

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Project description:BackgroundGrowing evidence supports the role of gut microbiota in obesity and its related disorders including type 2 diabetes. Ob/ob mice, which are hyperphagic due to leptin deficiency, are commonly used models of obesity and were instrumental in suggesting links between gut microbiota and obesity. Specific changes in their gut microbiota such as decreased microbial diversity and increased Firmicutes to Bacteroidetes ratio have been suggested to contribute to obesity via increased microbiota capacity to harvest energy. However, the differential development of ob/ob mouse gut microbiota compared to wild type microbiota and the role of hyperphagia in their metabolic impairment have not been investigated thoroughly.ResultsWe performed a 10-week long study in ob/ob (n = 12) and wild type control (n = 12) mice fed ad libitum. To differentiate effects of leptin deficiency from hyperphagia, we pair-fed an additional group of ob/ob mice (n = 11) based on the food consumption of control mice. Compared to control mice, ob/ob mice fed ad libitum exhibited compromised glucose metabolism and increased body fat percentage. Pair-fed ob/ob mice exhibited even more compromised glucose metabolism and maintained strikingly similar high body fat percentage at the cost of lean body mass. Acclimatization of the microbiota to our facility took up to 5 weeks. Leptin deficiency impacted gut microbial composition, explaining 18.3% of the variance. Pair-feeding also altered several taxa, although the overall community composition at the end of the study was not significantly different. We found 24 microbial taxa associations with leptin deficiency, notably enrichment of members of Lactobacillus and depletion of Akkermansia muciniphila. Microbial metabolic functions related to energy harvest, including glycan degradation, phosphotransferase systems and ABC transporters, were enriched in the ob/ob mice. Taxa previously reported as relevant for obesity were associated with body weight, including Oscillibacter and Alistipes (both negatively correlated) and Prevotella (positively correlated).ConclusionsLeptin deficiency caused major changes in the mouse gut microbiota composition. Several microbial taxa were associated with body composition. Pair-fed mice maintained a pre-set high proportion of body fat despite reduced calorie intake, and exhibited more compromised glucose metabolism, with major implications for treatment options for genetically obese individuals.

Dataset Information

Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction.

Publications

Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction.

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