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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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Propensity to regain weight following weight loss: summary of data from a meta-analysis of US weight loss studies. The percentage of lost weight that is regained over a 5-year period according to a meta-analysis of 29 human weight loss studies. Adapted from Ref. (61).
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Figure 7: Propensity to regain weight following weight loss: summary of data from a meta-analysis of US weight loss studies. The percentage of lost weight that is regained over a 5-year period according to a meta-analysis of 29 human weight loss studies. Adapted from Ref. (61).

Mentions: Our studies of DIO rats in this weight regain paradigm have also examined the later stages of the relapse process to provide a more complete biological picture of weight regain after weight loss. We were interested in following the resolution of the energy gap, non-protein RQ, fuel utilization, and the energetic efficiency of weight regain. The pattern of regain in our rat paradigm reflected the pattern of regain in a meta-analysis of a large number of human regain studies (61), which some have suggested reflects a first-order relationship in the resolution of this biological drive (Figure 7). Our observations extended our previous findings by showing that the enhanced metabolic efficiency and suppressed TEE persist throughout the process of relapse. Both increased intake and suppressed expenditure led to a large energy imbalance, or energy gap, which resolves gradually as the weight returns (Figure 7). While intake returns to levels observed before weight loss, TEE and REE never completely resolved even after the rats had returned to their previous weight. Both the reduction in feed efficiency and the elevation in non-protein RQ declined after week 2, suggesting that this efficient weight gain and shift in fuel use was most profound early in relapse when much of the lost weight returns (56). As expected, we and others have observed, at least in males, that exercise and physical activity attenuates the biological drive to regain weight early in relapse and leads to a lower body weight and fat mass (55, 59, 60). These studies support the notion that in males, exercise attenuates the drive to eat and increases expended energy above and beyond the additional energetic cost of the exercise bout, and that these effects persist throughout the entire relapse process. However, we have also observed that these beneficial effects of exercise may be greatly diminished if weight regain occurs on an obesogenic diet (62).


Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females
Propensity to regain weight following weight loss: summary of data from a meta-analysis of US weight loss studies. The percentage of lost weight that is regained over a 5-year period according to a meta-analysis of 29 human weight loss studies. Adapted from Ref. (61).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Propensity to regain weight following weight loss: summary of data from a meta-analysis of US weight loss studies. The percentage of lost weight that is regained over a 5-year period according to a meta-analysis of 29 human weight loss studies. Adapted from Ref. (61).
Mentions: Our studies of DIO rats in this weight regain paradigm have also examined the later stages of the relapse process to provide a more complete biological picture of weight regain after weight loss. We were interested in following the resolution of the energy gap, non-protein RQ, fuel utilization, and the energetic efficiency of weight regain. The pattern of regain in our rat paradigm reflected the pattern of regain in a meta-analysis of a large number of human regain studies (61), which some have suggested reflects a first-order relationship in the resolution of this biological drive (Figure 7). Our observations extended our previous findings by showing that the enhanced metabolic efficiency and suppressed TEE persist throughout the process of relapse. Both increased intake and suppressed expenditure led to a large energy imbalance, or energy gap, which resolves gradually as the weight returns (Figure 7). While intake returns to levels observed before weight loss, TEE and REE never completely resolved even after the rats had returned to their previous weight. Both the reduction in feed efficiency and the elevation in non-protein RQ declined after week 2, suggesting that this efficient weight gain and shift in fuel use was most profound early in relapse when much of the lost weight returns (56). As expected, we and others have observed, at least in males, that exercise and physical activity attenuates the biological drive to regain weight early in relapse and leads to a lower body weight and fat mass (55, 59, 60). These studies support the notion that in males, exercise attenuates the drive to eat and increases expended energy above and beyond the additional energetic cost of the exercise bout, and that these effects persist throughout the entire relapse process. However, we have also observed that these beneficial effects of exercise may be greatly diminished if weight regain occurs on an obesogenic diet (62).

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