Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Anson, R. Michael; Guo, Zhihong; Cabo, Rafael de; Iyun, Titilola; Rios, Michelle; Hagepanos, Adrienne; Ingram, Donald K.; Lane, Mark A.; Mattson, Mark P.

doi:10.1073/pnas.1035720100

Cited by 607 publications

(564 citation statements)

References 41 publications

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“…During the experiment the INT‐fed mice weekly lose or gain ∼15% of their body weight. This fluctuating pattern is maintained from 9 weeks till 24 months of age, which is much longer than the time interval applied in most other studies examining intermittent fasting/CR 9, 17, 30, 63, 64 and allows us to explore the effects induced at both young and old age. To check whether this dietary variant could prevent against the adverse health effects caused by an obesogenic diet during the ad libitum feeding week we included a MF instead of a control diet.…”

Section: Discussionmentioning

confidence: 99%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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ScopeCalorie restriction (CR) has been shown to extend life‐ and health‐span in model species. For most humans, a life‐long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can (1) provide long‐term beneficial effects and (2) counteract diet‐induced obesity in male aging mice.Methods and resultsIn this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate‐fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight, and liver health markers in 24‐month‐old male mice. Hepatic gene expression profiles of INT‐exposed animals appeared much more comparable to CR‐ than to MF‐exposed mice. At 12 months of age, a subgroup of MF‐exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24‐month‐old diet switch mice were highly similar to the INT‐exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.ConclusionWeekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.

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Section: Discussionmentioning

confidence: 99%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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“…There is currently great interest in treatment approaches to improve insulin signaling and glucose metabolism in AD, including glucagon like peptide (GLP‐1) mimetics such as exendin‐4 (see clinical trial NCT01255163) and also66), intranasal insulin67 and calorie restriction diets 68. MRS biomarkers that reflect the metabolic status of the brain may be better suited to demonstrate target engagement and follow response to treatment compared to biomarkers reflecting amyloid and Tau pathologies in AD.…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

Mullins

Reiter

Kapogiannis

2018

Ann Clin Transl Neurol

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ObjectiveBrain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case–control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD‐related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites.MethodsJ‐modulated Point‐Resolved Spectroscopy (J‐PRESS) and Prior‐Knowledge Fitting (ProFit) software was used to measure glucose and other metabolites in the posterior cingulate/precuneus of 25 AD, 27 older controls, and 27 younger control participants. Clinical assessments for AD participants included cognitive performance measures, insulin resistance metrics and CSF biomarkers.Results AD participants showed substantially elevated glucose, lactate, and ascorbate levels compared to older (and younger) controls. In addition, the precuneal glucose elevation discriminated well between AD participants and older controls. Myo‐inositol correlated with CSF p‐Tau181P, total Tau, and the Clinical Dementia Rating (CDR) sum‐of‐boxes score within the AD group.InterpretationHigher glucose to creatine ratios in the AD brain likely reflect lower glucose utilization. Our findings reveal pronounced metabolic abnormalities in the AD brain and strongly suggest that brain glucose merits further investigation as a candidate AD biomarker.

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“…Interestingly, this prediction has not been borne out. This somewhat surprising discovery was published in 2003 (Anson et al 2003): even without a net decrease in weekly caloric consumption (Figure 1), C57BL/6J mice fed IF (EOD) exhibited much of the CR effect. In that study, the LD and EOD paradigms were compared.…”

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confidence: 86%

“…When a full-grown organism is initially Figure 1. Male C57BL/6 mice compensate for periods of fasting by increasing their food intake and gaining weight at rates similar to mice fed ad libitum (Anson et al 2003). Average daily food intakes (calculated from 14-day intake) (a) and bodyweights (b) in mice maintained on one of four feeding regimens: ad libitum (AL), intermittent fasting (IF; alternate day feeding), pair-fed to the IF group (PF) and limited daily feeding (LDF; 40% reduction in calories relative to AL).…”

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confidence: 99%

The diet restriction paradigm: a brief review of the effects of every-other-day feeding

Anson

Jones

Cabod

2005

AGE

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It has been known since the early 1900s that restriction of dietary intake relative to the ad libitum (AL) level increases stress resistance, cancer resistance, and longevity in many species. Studies investigating these phenomena have used three paradigms for dietary restriction. In the first, the AL intake of a control group is measured, and an experimental group is fed less than that amount in a specified proportion, e.g., 40%. In the second, food is provided AL to both the control and experimental groups: however, the experimental group is subjected to periods of fasting. Recent studies using this paradigm provide food every other day (EOD). Both of these paradigms have been in use since the early 1900s. A third paradigm that combines them was developed in the early 1970s: one or more days of fasting separate the provision of a limited amount of food. It was assumed for many years that the physiological responses to these paradigms were due exclusively to a net decrease in energy intake. Recently, however, it was found that some species and strains of laboratory animals, when fed AL every other day, are capable of gorging so that their net weekly intake is not greatly decreased. Despite having only a small deficit in energy intake relative to control levels, however, these animals experience enhanced longevity and stress resistance in comparison to AL controls as much as in animals enduring daily restriction of diet. These observations warrant renewed interest in this paradigm and suggest that comparisons of the paradigms and their effects can be used to determine which factors are critical to the beneficial effects of caloric restriction.Many species age more quickly with an ad libitum food intake than with one that is restricted, and the mechanism underlying this effect remains unidentified

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Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

Cited by 607 publications

References 41 publications

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

The diet restriction paradigm: a brief review of the effects of every-other-day feeding

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