Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice

Selman, Colin; Hempenstall, Sarah

doi:10.1186/2046-2395-1-2

Cited by 26 publications

(34 citation statements)

References 49 publications

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“…This switch allowed thorough examination of persistence of the CR-induced effects upon challenging conditions. Previous studies showed that favourable metabolic effects of CR, such as an improved glucose tolerance, are persistent after discontinuation of prolonged CR [26,27]. In our study, we have seen that most gene expression profiles, relative abundance of microbial genera and levels of metabolites adapted to patterns of the MF mice after the diet switch.…”

Section: Discussionsupporting

confidence: 61%

“…However, detailed insight into persistence of CR-induced effects upon challenging conditions is scarce [25]. It has been demonstrated that favourable metabolic effects are persistent after discontinuation of prolonged CR [26,27]. To what extent this 'metabolic memory' also applies to the colon, and whether CR-induced effects on markers of colonic health are persistent, is not known.…”

Section: Introductionmentioning

confidence: 99%

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Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Kok

Lugt

Lute

et al. 2018

The Journal of Nutritional Biochemistry

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Diminished colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an effective strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here, we report the effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice. Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was associated with attenuated immune- and inflammation-related gene expression in the colon. Furthermore, expression of genes involved in lipid metabolism was higher upon CR, which may point towards efficient regulation of energy metabolism. The relative abundance of bacteria considered beneficial to colonic health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed to CR for 28 months as compared to the other diet groups. We found lower plasma levels of interleukin-6 and lower levels of various metabolites, among which are bile acids, in the colonic luminal content of CR-exposed mice as compared to the other diet groups. Switching from CR to an ad libitum moderate-fat diet at old age (24 months) revealed remarkable phenotypic plasticity in terms of gene expression, microbiota composition and metabolite levels, although expression of a subset of genes remained CR-associated. This study demonstrated in a comprehensive way that CR affects indicators of colonic health in aging mice. Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, which may contribute to healthy aging.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Kok

Lugt

Lute

et al. 2018

The Journal of Nutritional Biochemistry

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“…The lifelong CR‐exposed mice in our aging cohort demonstrated their anticipation to receiving their daily food allotment by a burst in their activity level just prior to the regularly scheduled feeding (Van Norren et al., ). The hyperphagic response is an indicator that hunger persists even after a long‐term CR (Hambly, Mercer, & Speakman, ) and is maintained until body weight reaches the level of the ad libitum ‐fed animals (Selman & Hempenstall, ). It is followed by a dramatic weight gain, adipose tissue expansion, and hepatic steatosis.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of lifelong calorie‐restricted C57BL/6J mice in adapting to a medium‐fat diet intervention at old age

et al. 2017

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SummaryCalorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver‐specific responses caused by a diet switch to a medium‐fat (MF) diet in 24‐month‐old lifelong, CR‐exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine‐week‐old C57BL/6J mice were exposed either to a control, CR, or MF diet. At the age of 24 months, a subset of mice of the CR group was transferred to ad libitum MF feeding (CR‐MF). The mice were sacrificed at the age of 28 months, and then, biochemical and molecular analyses were performed. Our results showed that, despite the long‐term exposure to the CR regimen, mice in the CR‐MF group displayed hyperphagia, rapid weight gain, and hepatic steatosis. However, no hepatic fibrosis/injury or alteration in CR‐improved survival was observed in the diet switch group. The liver transcriptomic profile of CR‐MF mice largely shifted to a profile similar to the MF‐fed animals but leaving ~22% of the 1,578 differentially regulated genes between the CR and MF diet groups comparable with the expression of the lifelong CR group. Therefore, although the diet switch was performed at an old age, the CR‐MF‐exposed mice showed plasticity in coping with the challenge of a MF diet without developing severe liver pathologies.

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“…There is evidence that some physiological effects of dietary restriction, the most well-studied method to extend lifespan, are retained after this treatment is ended. For example, dietary restricted mice that are subsequently switched to an ad libitum diet retain significantly improved markers of glucose metabolism for months after this dietary modulation [40, 41]. In contrast though, the switch from dietary restricted to ad libitum feeding has also been shown to rapidly increase oxidative damage and alter the transcriptome to that of mice fed ad libitum their entire life [42, 43].…”

Section: Discussionmentioning

confidence: 99%

Rapamycin-induced metabolic defects are reversible in both lean and obese mice

Liu

Diaz

Fernández

et al. 2014

Aging

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The inhibition of mTOR (mechanistic target of rapamycin) by the macrolide rapamycin has many beneficial effects in mice, including extension of lifespan and reduction or prevention of several age-related diseases. At the same time, chronic rapamycin treatment causes impairments in glucose metabolism including hyperglycemia, glucose intolerance and insulin resistance. It is unknown whether these metabolic effects of rapamycin are permanent or whether they can be alleviated. Here, we confirmed that rapamycin causes glucose intolerance and insulin resistance in both inbred and genetically heterogeneous mice fed either low fat or high fat diets, suggesting that these effects of rapamycin are independent of genetic background. Importantly, we also found that these effects were almost completely lost within a few weeks of cessation of treatment, showing that chronic rapamycin treatment does not induce permanent impairment of glucose metabolism. Somewhat surprisingly, chronic rapamycin also promoted increased accumulation of adipose tissue in high fat fed mice. However, this effect too was lost when rapamycin treatment was ended suggesting that this effect of rapamycin is also not permanent. The reversible nature of rapamycin's alterations of metabolic function suggests that these potentially detrimental side-effects might be managed through alternative dosing strategies or concurrent treatment options.

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Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice

Cited by 26 publications

References 49 publications

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Plasticity of lifelong calorie‐restricted C57BL/6J mice in adapting to a medium‐fat diet intervention at old age

Rapamycin-induced metabolic defects are reversible in both lean and obese mice

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