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

ABSTRACT: Calorie 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.In 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.Weekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.

SUBMITTER: Rusli F

PROVIDER: S-EPMC6120141 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Rusli Fenni F Lute Carolien C Boekschoten Mark V MV van Dijk Miriam M van Norren Klaske K Menke Aswin L AL Müller Michael M Steegenga Wilma T WT

Molecular nutrition & food research 20170321 5

<h4>Scope</h4>Calorie 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.<h4>Methods and results</h4>In this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a contr ...[more]

PMID: 27995741

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Project description:Background & aimsThe first-line treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction. Several diets have been proposed, with various effects specifically on liver steatosis. This trial compared the effects of intermittent calorie restriction (the 5:2 diet) and a low-carb high-fat diet (LCHF) on reduction of hepatic steatosis.MethodsWe conducted an open-label randomised controlled trial that included 74 patients with NAFLD randomised in a 1:1:1 ratio to 12 weeks' treatment with either a LCHF or 5:2 diet, or general lifestyle advice from a hepatologist (standard of care; SoC). The primary outcome was reduction of hepatic steatosis as measured by magnetic resonance spectroscopy. Secondary outcomes included transient elastography, insulin resistance, blood lipids, and anthropometrics.ResultsThe LCHF and 5:2 diets were both superior to SoC treatment in reducing steatosis (absolute reduction: LCHF: -7.2% [95% CI = -9.3 to -5.1], 5:2: -6.1% [95% CI = -8.1 to -4.2], SoC: -3.6% [95% CI = -5.8 to -1.5]) and body weight (LCHF: -7.3 kg [95% CI = -9.6 to -5.0]; 5:2: -7.4 kg [95% CI = -8.7 to -6.0]; SoC: -2.5 kg [95% CI =-3.5 to -1.5]. There was no difference between 5:2 and LCHF (p = 0.41 for steatosis and 0.78 for weight). Liver stiffness improved in the 5:2 and SoC but not in the LCHF group. The 5:2 diet was associated with reduced LDL levels and was tolerated to a higher degree than LCHF.ConclusionsThe LCHF and 5:2 diets were more effective in reducing steatosis and body weight in patients with NAFLD than SoC, suggesting dietary advice can be tailored to meet individual preferences.Lay summaryFor a person with obesity who suffers from fatty liver, weight loss through diet can be an effective treatment to improve the condition of the liver. Many popular diets that are recommended for weight reduction, such as high-fat diets and diets based on intermittent fasting, have not had their effects on the liver directly evaluated. This study shows that both a low-carb high-fat and the 5:2 diet are effective in treating fatty liver caused by obesity.Clinical trials registrationThis study is registered at Clinicaltrials.gov (NCT03118310).

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

Publications

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

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