Abstract

Over the past 50 years, dietary restriction (DR) has been shown to extend the life span of a wide variety of organisms. A hallmark feature of DR is improved glucose homeostasis resulting in increased glucose tolerance and insulin sensitivity of animals ranging from rodents to humans. In this study, we demonstrate the early effects of varying levels of DR on glucose tolerance. Within 10 days of 40% DR, glucose tolerance was significantly improved and by 120 days; 10 and 20% DR also showed enhanced glucose tolerance. All three levels of DR showed reduced adiposity, increased expression of genes involved in fat turnover, and a reduction in the expression for markers of inflammation. Studies have shown that mice fed a DR diet retained metabolic memory in terms of improved glucose tolerance even after DR is discontinued. We show that 40% DR not only has an early effect on glucose tolerance but also maintained it after DR was discontinued for 2 months. Therefore, improvement in glucose tolerance is brought about by all three levels of DR but the metabolic memory is not dose responsive.

Highlights

  • The first and most studied manipulation shown to increase life span in mammals is dietary/caloric restriction

  • Research over the past two decades shows that Dietary restriction (DR) increases the life span of a wide variety of other organisms ranging from invertebrates, such as yeast, C. elegans, and Drosophila, as well as spiders and rotifers to various strains of rats and mice (Weindruch and Walford 1988; Swindell 2012)

  • We investigated the early effect of DR on the body weight and body composition of male C57BL/6 mice fed three levels of DR (10, 20, and 40% DR)

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Summary

Introduction

The first and most studied manipulation shown to increase life span in mammals is dietary/caloric restriction. Dietary restriction (DR) was first shown to increase the life span of rats and subsequently various strains of mice. Research over the past two decades shows that DR increases the life span of a wide variety of other organisms ranging from invertebrates, such as yeast, C. elegans, and Drosophila, as well as spiders and rotifers to various strains of rats and mice (Weindruch and Walford 1988; Swindell 2012). DR has been reported to increase the life span of other types of mammals such as Labrador Retrievers (Kealy et al 2002) and Rhesus monkeys (Colman et al 2009). Two recent studies suggest that lower levels of DR are as effective in increasing life span as 40% DR. Mitchell et al (2016) showed that 20% DR was as effective and in some cases more effective than 40% DR, at increasing life span in C57BL/6 and DBA/2 mice

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