Research article
Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction

https://doi.org/10.1016/j.jnutbio.2008.11.001Get rights and content

Abstract

Calorie restriction (CR) and alternate-day fasting (ADF) beneficially affect several aspects of adipose tissue physiology, but direct comparisons between regimens have yet to be performed. The present study evaluated the effects of ADF versus CR on body fat distribution and circulating adiponectin levels and examined the kinetic mechanisms that underlie changes in fat distribution. Thirty female C57BL/6J mice were randomized to one of five groups for 4 weeks: (a) CR-25% (25% energy restriction daily), (b) ADF-75% (75% restriction on fast day), (c) ADF-85% (85% restriction on fast day), (d) ADF-100% (100% restriction on fast day) and (e) control (ad libitum fed). Body weights of the CR mice were lower than that of the ADF and control groups posttreatment. After 4 weeks of diet, the proportion of visceral fat decreased (P<.001) and the proportion of subcutaneous fat increased (P<.001) similarly in ADF and CR animals. Adiponectin increased (P<.05) by 62–86% in the ADF groups and by 69% in the CR group. Triglyceride (TG) synthesis and de novo lipogenesis were augmented (P<.05) in the subcutaneous fat pad of ADF and CR animals, relative to control. No differences in net lipolysis were observed, resulting in greater TG accumulation in the subcutaneous fat pad, with a shift in the ratio of TG between depots. These findings indicate that ADF (both modified and true) produces similar beneficial modulations in body fat distribution and adiponectin levels as daily CR.

Introduction

The role of regional fat distribution in the development of certain obesity-related disorders, such as type 2 diabetes and cardiovascular disease, has been firmly established [1]. Visceral obesity, characterized in humans by increased intra-abdominal fat mass at the lumbosacral level, is associated with a higher incidence of insulin resistance, cardiovascular events and premature death [2], [3]. In contrast, individuals with increased adipose mass in subcutaneous gluteofemoral depots exhibit lower risk of developing these adverse outcomes than those with comparable amounts of adipose tissue in visceral depots [4]. A mechanism that may link fat distribution to disease risk is adipokine secretion profile. Adiponectin, a hormone mainly expressed by adipose tissue, exhibits both antiatherogenic and insulin-sensitizing effects [5]. Circulating levels of this adipokine have been shown to be inversely correlated with visceral fat mass [6]. Leptin, another adipocyte-derived protein, plays a key role in glucose and lipid metabolism and, hence, may modulate risk of chronic disease [7]. Leptin levels are related to body fat distribution, as mRNA levels and secretion rates are higher in subcutaneous adipocytes, when compared to those from visceral compartments [7].

Dietary interventions that reduce daily energy intake, also known as calorie restriction (CR), have been shown to cause numerous physiological benefits in both animals and humans [8]. Recent evidence with these regimens suggests that CR reduces visceral adipose mass even in nonobese individuals [9]. These CR-induced decreases in visceral fat are accompanied by significant increases in adiponectin [10]. Alternate-day fasting (ADF) represents another form of dietary restriction. ADF consists of alternating 24-h periods of ad libitum feeding and fasting and reproduces several of the physiological benefits of CR [11]. Recently, we demonstrated that true ADF, that is, complete energy deprivation on the fast day, reduced fat cell size by ∼35% to 55% in both visceral and subcutaneous adipose tissue depots after 4 weeks in mice [12]. Since smaller fat cells are associated with cardioprotection and insulin sensitivity compared to larger fat cells [13], [14], these preliminary results suggest that ADF may have beneficial effects on the qualitative features of adipose tissue. The effect of ADF versus CR on fat distribution and resultant adiponectin and leptin release has yet to be clarified, however. Moreover, if redistribution of adipose tissue from visceral to subcutaneous sites occurs, the kinetic and metabolic basis has yet to be elucidated.

Accordingly, the primary objective of this study was to compare the effects of ADF versus CR on body fat distribution and circulating adiponectin levels and to uncover the dynamic metabolic mechanisms that underlie these changes. Additionally, we examined the day-to-day variation in adipose tissue triglyceride (TG) metabolism in response to alternating days of feeding and fasting. We hypothesize that ADF will be equally as effective as CR in reducing visceral adiposity and increasing subcutaneous adiposity. These changes in fat distribution will be associated with higher circulating adiponectin and leptin concentrations in both the ADF and CR groups.

Section snippets

Study 1: effects of ADF versus CR on body fat distribution and adipokines

Seven-week-old C57BL/6J female mice (n=30, Charles River Breeding Laboratories, Wilmington, MA) were housed individually and maintained under temperature- and light-controlled conditions (12 h light/dark cycle: lights on at 0700 h and lights off at 1900 h). Mice were acclimatized for 1 week and allowed free access to water and a semipurified AIN-93M diet (Bio-Serv, Frenchtown, NJ) prior to initiation of studies. Mice were then randomized into one of five intervention groups: (a) CR-25% (food

Body weight in ADF versus CR mice

Changes in body weight over the course of the study are portrayed in Table 1. Body weights of each intervention group were similar during the first week of treatment. Mice in the CR-25% group weighed less (P<.05) than those in the ADF and control groups throughout the last 3 weeks of the study. Body weights of the ADF mice were similar to that of controls at all time points. Mice in the ADF and control groups gained weight (P<.05) over the 4-week study period.

Food intake in ADF versus CR mice

Mean weekly food intake in the CR

Discussion

We report here, for the first time, a redistribution of fat from visceral to subcutaneous depots, as a result of true and modified ADF in female C57BL/6J mice. We also show that this redistribution in fat by ADF is comparable to that of CR. The marked decrease in visceral fat was related to an increase in circulating adiponectin levels in all dietary restriction groups. This redistribution in fat was explained kinetically by an increase in TG synthesis and DNL in the subcutaneous fat pad of

Acknowledgments

We are grateful for the help of Simply Florcruz and Allen Dang during the animal phase of the study. There are no conflicts of interest to report.

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    Funding: Natural Science and Engineering Research Council of Canada; State of California Discovery (BioStar) Program.

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