| Description |
Determining the health impacts of a nutritional regimen, suspected toxicant or other treatment is often a difficult task in both the realms of safety assessment and basic research. There are far too many examples of agents, once considered safe, found later through epidemiology (or other means) to cause adverse health effects. To prevent such experimentation on ourselves there is a great societal need for broad, sensitive assays able to detect toxicity at human-relevant exposure levels. Similarly, basic researchers often lack the experimental tools necessary to determine if a treatment adversely impacts the health of their model organism. We argue that these problems can be partially solved by using house mice in the crucible of their natural setting where they are challenged daily by the very tasks that have shaped them for millennia. Quantifying the lifelong fitness of experimentally treated animals directly competing with control individuals offers a sensitive and broad approach for detecting adverse health effects. We refer to this approach as an Organismal Performance Assay (OPA). To illustrate the effectiveness of OPAs, herein we apply them for detecting adverse health consequences of nutritional and toxic exposures. First, using OPAs we capture adverse health impacts (decreased survival, competitive ability and reproduction) from consuming 12.5% kcal of fructose; this finding now represent the lowest observed adverse effect level for dietary fructose. Next, we apply OPAs to determine if differential health impacts occur due to the consumption of one, or the other, of the two common types of added sugar, high fructose corn syrup (fructose and glucose monosaccharides) or table sugar (sucrose, which is a disaccharide of fructose and glucose), and show that the high fructose corn syrup diet increases mortality and decreases reproduction of female mice compared to sucrose, providing the first experimental evidence that the two most common forms of caloric sweeteners have differential health impacts. Next, we use OPAs to determine if an acute exposure to 3mg/kg of amine-terminated generation seven poly amido-amine dendrimers, the current maximum tolerated dose, is actually toxic and find that it is not. Finally, to address the criticism that OPAs do not lead to the underlying mechanisms of observed organismal outcomes, we illustrate the discovery of the molecular basis of the first phenomenon revealed using OPAs, major histocompatibility complex (MHC)-based mating preferences, which is done in the context of a review paper on the role of MHC during social communication. |
