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Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females

View Article: PubMed Central - PubMed

ABSTRACT

Obesity is a worldwide epidemic, and the comorbidities associated with obesity are numerous. Over the last two decades, we and others have employed an outbred rat model to study the development and persistence of obesity, as well as the metabolic complications that accompany excess weight. In this review, we summarize the strengths and limitations of this model and how it has been applied to further our understanding of human physiology in the context of weight loss and weight regain. We also discuss how the approach has been adapted over time for studies in females and female-specific physiological conditions, such as menopause and breast cancer. As excess weight and the accompanying metabolic complications have become common place in our society, we expect that this model will continue to provide a valuable translational tool to establish physiologically relevant connections to the basic science studies of obesity and body weight regulation.

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Related in: MedlinePlus

Rodent paradigm to study the metabolic propensity to regain weight after weight loss. This paradigm, employing obesity-prone rats, has well-defined primary and secondary outcomes that describe the metabolic propensity to regain weight after prolonged weight reduction. This approach can be applied to test weight reduction strategies for their ability to overcome the metabolic pressures driving weight regain by modifying the environmental conditions in the treatment phase and examining the response during the relapse phase.
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Figure 4: Rodent paradigm to study the metabolic propensity to regain weight after weight loss. This paradigm, employing obesity-prone rats, has well-defined primary and secondary outcomes that describe the metabolic propensity to regain weight after prolonged weight reduction. This approach can be applied to test weight reduction strategies for their ability to overcome the metabolic pressures driving weight regain by modifying the environmental conditions in the treatment phase and examining the response during the relapse phase.

Mentions: Over the past decade, we have employed the OR/OP model to study the phenomenon of weight regain after weight loss. The paradigm we developed to model the human condition is shown in Figure 4. Following the standardized screen to identify the OR and OP phenotypes described above, the young rats are maintained in the obesogenic environment (HF diet; limited physical activity) for 16 weeks, during which excessive weight gain occurs in what would be equivalent to childhood and adolescence. As the rats mature, growth rates slow, the gain in body weight and fat-free mass plateaus, and further weight gain comes slowly and primarily in the form of fat mass. The rats are then given a two-step treatment regimen (weight loss followed by weight maintenance) that reflects the most common approach used in humans: restricted consumption of an LF diet. The rats are fed a calorie-restricted LF diet that induces a 10–15% loss in weight that is primarily fat mass. A LF provision, adjusted on a daily basis, is given so that weight is maintained at this reduced level. In some studies, weight reduction has been sustained with intake-regulated maintenance for up to 16 weeks, a period of time that would reflect several years of weight reduction in humans (57). The propensity to regain weight is then characterized by allowing the rats to have free access to a specific diet while monitoring body weight, body composition, and pertinent aspects of metabolism as they relapse to the obese state. Our assertion is that this paradigm reflects the human condition with respect to:(1)


Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females
Rodent paradigm to study the metabolic propensity to regain weight after weight loss. This paradigm, employing obesity-prone rats, has well-defined primary and secondary outcomes that describe the metabolic propensity to regain weight after prolonged weight reduction. This approach can be applied to test weight reduction strategies for their ability to overcome the metabolic pressures driving weight regain by modifying the environmental conditions in the treatment phase and examining the response during the relapse phase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121240&req=5

Figure 4: Rodent paradigm to study the metabolic propensity to regain weight after weight loss. This paradigm, employing obesity-prone rats, has well-defined primary and secondary outcomes that describe the metabolic propensity to regain weight after prolonged weight reduction. This approach can be applied to test weight reduction strategies for their ability to overcome the metabolic pressures driving weight regain by modifying the environmental conditions in the treatment phase and examining the response during the relapse phase.
Mentions: Over the past decade, we have employed the OR/OP model to study the phenomenon of weight regain after weight loss. The paradigm we developed to model the human condition is shown in Figure 4. Following the standardized screen to identify the OR and OP phenotypes described above, the young rats are maintained in the obesogenic environment (HF diet; limited physical activity) for 16 weeks, during which excessive weight gain occurs in what would be equivalent to childhood and adolescence. As the rats mature, growth rates slow, the gain in body weight and fat-free mass plateaus, and further weight gain comes slowly and primarily in the form of fat mass. The rats are then given a two-step treatment regimen (weight loss followed by weight maintenance) that reflects the most common approach used in humans: restricted consumption of an LF diet. The rats are fed a calorie-restricted LF diet that induces a 10–15% loss in weight that is primarily fat mass. A LF provision, adjusted on a daily basis, is given so that weight is maintained at this reduced level. In some studies, weight reduction has been sustained with intake-regulated maintenance for up to 16 weeks, a period of time that would reflect several years of weight reduction in humans (57). The propensity to regain weight is then characterized by allowing the rats to have free access to a specific diet while monitoring body weight, body composition, and pertinent aspects of metabolism as they relapse to the obese state. Our assertion is that this paradigm reflects the human condition with respect to:(1)

View Article: PubMed Central - PubMed

ABSTRACT

Obesity is a worldwide epidemic, and the comorbidities associated with obesity are numerous. Over the last two decades, we and others have employed an outbred rat model to study the development and persistence of obesity, as well as the metabolic complications that accompany excess weight. In this review, we summarize the strengths and limitations of this model and how it has been applied to further our understanding of human physiology in the context of weight loss and weight regain. We also discuss how the approach has been adapted over time for studies in females and female-specific physiological conditions, such as menopause and breast cancer. As excess weight and the accompanying metabolic complications have become common place in our society, we expect that this model will continue to provide a valuable translational tool to establish physiologically relevant connections to the basic science studies of obesity and body weight regulation.

No MeSH data available.


Related in: MedlinePlus