Colony maintenance and the behavioral and physiological characteristics of selectively bred obesity prone and obesity resistant rats.

Abstract

Obesity arises from interactions between several factors including physiology, environment and genes. Studies in humans have revealed that up to 70% of overweight and obesity can be attributed to biological and genetic factors. Thus, rodent models that capture innate susceptibility or resistance to obesity have been invaluable for disentangling inherent drivers of obesity from neurobiological alterations that occur in response to consumption of obesogenic foods and/or increased adiposity. For example, studies of rats selectively bred for their propensity vs resistance to diet-induced weight gain (DIO and DR) have uncovered differences in hypothalamic circuits involved in leptin signaling and revealed relationships between susceptibility to obesity and motivational response to food cues, as well as inherent and diet-induced alterations in mesocorticolimbic systems that differ between these populations. Maintaining selectively bred lines in a closed breeding population requires the periodic introduction of new genes to avoid inbreeding. Here we describe a process for maintaining these lines, characterize key phenotypes across the selection process and verify weight gain and obesity phenotypes in the resulting colony. In addition, given the central role of the striatum in motivation for food, we examined basal striatal function and food motivation in these refreshed lines using whole-cell patch clamping and instrumental procedures. Key weight and metabolic phenotypes were maintained in the resulting colony, as was enhanced motivation for food in obesity prone rats. This provides a strong basis for examination of interactions between genes, environment and neurobehavioral plasticity that promote weight gain and obesity.