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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.

No MeSH data available.


Related in: MedlinePlus

Screening strategies for OP and OR phenotype in female Wistar rats. Female rats were individually housed in wire bottom cages and fed a HF diet (46% kcal fat) for the duration of the study. Body weight and body composition were measured throughout the study and was correlated with % body fat at the time of OVX (maturity; 26.5 ± 0.6 weeks of age). (A) Change in body weight early in life (8.5–9.5 weeks of age) is not a strong predictor of adult adiposity, but (B) % body fat at 14 weeks of age does predict adult adiposity.
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Figure 2: Screening strategies for OP and OR phenotype in female Wistar rats. Female rats were individually housed in wire bottom cages and fed a HF diet (46% kcal fat) for the duration of the study. Body weight and body composition were measured throughout the study and was correlated with % body fat at the time of OVX (maturity; 26.5 ± 0.6 weeks of age). (A) Change in body weight early in life (8.5–9.5 weeks of age) is not a strong predictor of adult adiposity, but (B) % body fat at 14 weeks of age does predict adult adiposity.

Mentions: As shown in Figure 2A, the correlation between the % BF at the time of OVX and weight gained from 8.5 to 9.5 weeks of age was poor (r = 0.43). This improved slightly when change in body weight was measured over 2 weeks (8.5–10.5 weeks of age, r = 0.59, data not shown) and was further improved when extended to 8 weeks (8.5–18.5 weeks of age, r = 0.69, data not shown). However, these changes in body weight were still not as predictive of adult adiposity as the <1 week weight gain was in numerous studies in the males described above. Thus, we investigated other potential measures that could be used to accurately screen for the OP and OR phenotypes in females. Change in % BF over the various time points were measured, but these correlations were no better than changes in body weight (r = 0.35–0.63, depending on the cohort of animals and time points measured). However, % BF at 14 weeks of age was highly correlated with adult adiposity (Figure 2B; r = 0.70–0.81, depending on the cohort). These correlations appeared to be stronger when controlling for the age at the time OVX body composition was analyzed (r = 0.79–0.84). At 18 weeks of age, the correlation strengthened even further (r = 0.89). However, in our opinion, the added time and cost associated with the additional month of animal housing to delay the separation is likely not warranted. Importantly, our data indicate that % BF early in life (9 weeks of age in this study) is not an accurate predictor of % BF at maturity (r = 0.54), and approximately one-third of rats would have been incorrectly categorized (OR, mid, OP) if this early marker of body composition was used. Additional studies will be required to further determine if a time point between 9 and 14 weeks is predictive of long-term adiposity. In the meantime, our approach is to refrain from screening until ~14 weeks of age to identify the OR and OP phenotypes in females.


Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females
Screening strategies for OP and OR phenotype in female Wistar rats. Female rats were individually housed in wire bottom cages and fed a HF diet (46% kcal fat) for the duration of the study. Body weight and body composition were measured throughout the study and was correlated with % body fat at the time of OVX (maturity; 26.5 ± 0.6 weeks of age). (A) Change in body weight early in life (8.5–9.5 weeks of age) is not a strong predictor of adult adiposity, but (B) % body fat at 14 weeks of age does predict adult adiposity.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Screening strategies for OP and OR phenotype in female Wistar rats. Female rats were individually housed in wire bottom cages and fed a HF diet (46% kcal fat) for the duration of the study. Body weight and body composition were measured throughout the study and was correlated with % body fat at the time of OVX (maturity; 26.5 ± 0.6 weeks of age). (A) Change in body weight early in life (8.5–9.5 weeks of age) is not a strong predictor of adult adiposity, but (B) % body fat at 14 weeks of age does predict adult adiposity.
Mentions: As shown in Figure 2A, the correlation between the % BF at the time of OVX and weight gained from 8.5 to 9.5 weeks of age was poor (r = 0.43). This improved slightly when change in body weight was measured over 2 weeks (8.5–10.5 weeks of age, r = 0.59, data not shown) and was further improved when extended to 8 weeks (8.5–18.5 weeks of age, r = 0.69, data not shown). However, these changes in body weight were still not as predictive of adult adiposity as the <1 week weight gain was in numerous studies in the males described above. Thus, we investigated other potential measures that could be used to accurately screen for the OP and OR phenotypes in females. Change in % BF over the various time points were measured, but these correlations were no better than changes in body weight (r = 0.35–0.63, depending on the cohort of animals and time points measured). However, % BF at 14 weeks of age was highly correlated with adult adiposity (Figure 2B; r = 0.70–0.81, depending on the cohort). These correlations appeared to be stronger when controlling for the age at the time OVX body composition was analyzed (r = 0.79–0.84). At 18 weeks of age, the correlation strengthened even further (r = 0.89). However, in our opinion, the added time and cost associated with the additional month of animal housing to delay the separation is likely not warranted. Importantly, our data indicate that % BF early in life (9 weeks of age in this study) is not an accurate predictor of % BF at maturity (r = 0.54), and approximately one-third of rats would have been incorrectly categorized (OR, mid, OP) if this early marker of body composition was used. Additional studies will be required to further determine if a time point between 9 and 14 weeks is predictive of long-term adiposity. In the meantime, our approach is to refrain from screening until ~14 weeks of age to identify the OR and OP phenotypes 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.

No MeSH data available.


Related in: MedlinePlus