Ebook Potential Long-Term Consequences of Fad Diets on Health, Cancer, and Longevity: Lessons Learned from Model Organism Studies
Obesity is a major public health problem throughout the developed world, but it is especially troubling in children of the relatively affluent. In the US, the rate of children with obesity has increased from 5% in 1960 to 15% in 2000 (2). Associated with this increase in obesity is an increase in type II diabetes mellitus in children and adolescents, which many researchers believe may be triggered by obesity (3). It is likely that this childhood obesity “epidemic” presages a significant increase in other adult obesity associated maladies, such as blindness, heart disease, renal disorders, and even cancer (4). However, despite the urgent need for more knowledge, the potential long-term effects of childhood obesity on adults are not well understood, nor is it known which of the several dietary regimens are optimal for controlling childhood and adult obesity.
The quote leading this review is from a recent influential article from Dansinger and colleagues in which they did a comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for effectiveness in terms of weight loss and heart disease reduction in adults (1). Surprisingly, this is one of the few studies where randomized analyses have been conducted, and no studies have yet been completed in children. Dansinger and colleagues did a small trial of 160 participants randomly assigned to either the Atkins (carbohydrate restriction), Zone (macronutrient balance), Weight Watchers (caloric restriction), or Ornish (fat restriction) diet groups, with 40 participants in each group (1). The conclusion of this relatively unique, albeit admittedly underpowered, study is, “Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year. Overall dietary adherence rates were low, although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group” (1).
While this study received a great deal of press coverage, it is unfortunate that the low power of this study, because of the small number of people enrolled, the short time period for data accumulation, and the low participation rate of those enrolled, makes the conclusions tenuous at best. Unfortunately, human clinical studies, such as this, because of the enormous expense and Internal Review Board (IRB) requirements, are difficult for the average laboratory to conduct. Indeed, a more extensive study than that conducted by Dansinger and colleagues would be a major undertaking and take an enormous institutional and financial commitment.
One solution to the enormous expense and difficulties of human clinical studies on dietary interventions to combat childhood and adult obesity would be to increase the number obesity research studies in model organisms. The obesity epidemic justifies the need to study the long-term effects of different dietary regimens on morbidities associated with obesity, such as cancer, cardiovascular disease, and type II diabetes in non-human animal models. While most of the studies on obesity and nutrigenomics, the field of nutrient-gene interactions, have been done with mice and rats (e.g., (5)), in this review we argue that Drosophila is also a suitable model for some aspects of obesity and nutrigenomics. Drosophila might also be useful to determine the effects of fad diets on the long-term health of an organism (6, 7).
While Drosophila apparently do not suffer from obesity, nor do they have a four-chambered heart or even a closed vasculature which one might presume would be a prerequisite for cardiovascular disease research, the advantages of doing nutrigenomics research in flies are nevertheless numerous (6, 7). One advantage of using simple invertebrate models such as flies is that Drosophila store triglycerides primarily in their fat bodies (8-10) and, as in humans, a combination of both diet and genetics affect the circulating and stored triglyceride levels (e.g., (11-14)). Furthermore, over 70% of human disease genes are present in Drosophila and many of these diseases have already been modeled in Drosophila.
Future studies on those diseases that have not yet been modeled in flies are facilitated by the fact that over half of the genes have already been knocked out in Drosophila, and deficiencies spanning relatively small chromosomal regions with defined endpoints, many in a well-controlled isogenetic (i.e., genetically uniform) background, uncover over 95% of the genome (15). The Drosophila genome is arguably the most-well annotated and accessible such that stocks containing a majority of the mutant alleles are available from public accessible stock centers. These advantages, combined with the small sequenced genome, advanced genetics, and short lifespan make Drosophila a powerful nutrigenomics model (7). In this review, we present a short summary of dietary studies in Drosophila and present exciting future prospects for this organism in the obesity field.
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