A weekly alternating diet between caloric restriction and medium fat protects the liver from fatty liver development in middle-aged C57BL/6J mice.

Fenni Rusli,Mark V Boekschoten,Arantza Aguirre Zubia,Wilma T Steegenga,Michael Müller,Carolien Lute

doi:10.1002/mnfr.201400621

Fenni Rusli, Mark V Boekschoten + Show 4 more

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https://doi.org/10.1002/mnfr.201400621

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Abstract

ScopeWe investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet.Methods and resultsNine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight.ConclusionsOur study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice.

Highlights

Body weight gain in the C- and MF-fed mice included a significant increase in adiposity measured by the amount of white adipose tissue present in WAT, compared to the Calorie restriction diet (CR)- and INT-fed mice (p < 0.001, Fig. 1B)
We showed that a weekly alternating diet consisting of 40E% CR and ad libitum feeding of a MF (25E%) diet prevented development of Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), which was induced by life-long exposure to a MF diet and even the low-fat C diet
The prevalence of NAFLD has been shown to increase with advancing age and this indicates that the adverse effect of Western diet accumulates over many years [34,35,36,37]

Summary

Introduction

The modern Western-style diet and sedentary lifestyle often promote a positive energy balance, which has importantly contributed to the global rapid increase in the prevalence of metabolic syndrome in the recent decades [1,2,3,4]. Nonalcoholic fatty liver disease (NAFLD), a condition in which the liver excessively accumulates fat, has been considered as a hepatic manifestation of metabolic syndrome. The increasing prevalence of metabolic syndrome and NAFLD becomes a major concern [5,6] and implies an urgent need for a feasible and effective dietary intervention to prevent NAFLD [7]. Calorie restriction diet (CR) is widely known for its beneficial effects on health that is consistently demonstrated in various species [8,9,10], and these beneficial effects .

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