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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

Prospective analysis of the energy gap during weight regain with and without exercise. Energy balance [energy intake – total energy expenditure (EI-TEE)] is shown for obese, weight reduced, and relapsing rats either with (EX) or without (SED) treadmill exercise for several time periods during relapse. During weight regain, the energy gap (energy imbalance) resolves gradually as body weight is gained. Further, exercise reduces the energy gap both by suppressing EI and increasing TEE. *Significant difference between SED and EX rats during that time period, P < 0.05. Modified from Ref. (55).
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Figure 6: Prospective analysis of the energy gap during weight regain with and without exercise. Energy balance [energy intake – total energy expenditure (EI-TEE)] is shown for obese, weight reduced, and relapsing rats either with (EX) or without (SED) treadmill exercise for several time periods during relapse. During weight regain, the energy gap (energy imbalance) resolves gradually as body weight is gained. Further, exercise reduces the energy gap both by suppressing EI and increasing TEE. *Significant difference between SED and EX rats during that time period, P < 0.05. Modified from Ref. (55).

Mentions: To examine this critical early period, energy balance, fuel utilization, and regain were monitored prospectively through the first 2 weeks of relapse. During this time, almost half of the lost weight had been regained (34). We observed that both an increase in drive to eat and a decrease in expenditure contributed to the large energy gap, and neither side of the energy balance equation had normalized by the end of 2 weeks. Enhanced metabolic efficiency persisted throughout this early period of relapse and contributed to the suppressed TEE. In other studies, we utilized nutrient tracers in combination with metabolic phenotyping to examine fuel trafficking during the early stages of weight regain (58). During weight regain, we observed that the oxidation of dietary fat was substantially suppressed and that ingested fat was preferentially trafficked to adipose tissue for storage. Accompanying this shift in metabolism early in relapse was an increased number of small adipocytes, which would presumably provide an ideal receptacle for the excess ingested energy. When taken together, observation of DIO rats in this paradigm of weight regain suggest that adaptive changes in muscle and adipose tissue establish a metabolic context for rapid, energetically efficient weight regain. In subsequent studies, we have observed how regular exercise counters this metabolic drive to regain weight early in relapse; exercise decreases the energy imbalance or energy gap (Figure 6) both by reducing appetite and by increasing the level of expended energy during weight regain (55). Using nutrient tracers, we provided evidence suggesting that regular exercise increases the oxidation of dietary fat and traffics excess energy through more expensive pathways of deposition (59, 60). We have examined the tissue-specific mechanisms of these beneficial effects of exercise in both skeletal muscle (59) and adipose (60), and our analysis of the effects in liver will be forthcoming.


Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females
Prospective analysis of the energy gap during weight regain with and without exercise. Energy balance [energy intake – total energy expenditure (EI-TEE)] is shown for obese, weight reduced, and relapsing rats either with (EX) or without (SED) treadmill exercise for several time periods during relapse. During weight regain, the energy gap (energy imbalance) resolves gradually as body weight is gained. Further, exercise reduces the energy gap both by suppressing EI and increasing TEE. *Significant difference between SED and EX rats during that time period, P < 0.05. Modified from Ref. (55).
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Related In: Results  -  Collection

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

Figure 6: Prospective analysis of the energy gap during weight regain with and without exercise. Energy balance [energy intake – total energy expenditure (EI-TEE)] is shown for obese, weight reduced, and relapsing rats either with (EX) or without (SED) treadmill exercise for several time periods during relapse. During weight regain, the energy gap (energy imbalance) resolves gradually as body weight is gained. Further, exercise reduces the energy gap both by suppressing EI and increasing TEE. *Significant difference between SED and EX rats during that time period, P < 0.05. Modified from Ref. (55).
Mentions: To examine this critical early period, energy balance, fuel utilization, and regain were monitored prospectively through the first 2 weeks of relapse. During this time, almost half of the lost weight had been regained (34). We observed that both an increase in drive to eat and a decrease in expenditure contributed to the large energy gap, and neither side of the energy balance equation had normalized by the end of 2 weeks. Enhanced metabolic efficiency persisted throughout this early period of relapse and contributed to the suppressed TEE. In other studies, we utilized nutrient tracers in combination with metabolic phenotyping to examine fuel trafficking during the early stages of weight regain (58). During weight regain, we observed that the oxidation of dietary fat was substantially suppressed and that ingested fat was preferentially trafficked to adipose tissue for storage. Accompanying this shift in metabolism early in relapse was an increased number of small adipocytes, which would presumably provide an ideal receptacle for the excess ingested energy. When taken together, observation of DIO rats in this paradigm of weight regain suggest that adaptive changes in muscle and adipose tissue establish a metabolic context for rapid, energetically efficient weight regain. In subsequent studies, we have observed how regular exercise counters this metabolic drive to regain weight early in relapse; exercise decreases the energy imbalance or energy gap (Figure 6) both by reducing appetite and by increasing the level of expended energy during weight regain (55). Using nutrient tracers, we provided evidence suggesting that regular exercise increases the oxidation of dietary fat and traffics excess energy through more expensive pathways of deposition (59, 60). We have examined the tissue-specific mechanisms of these beneficial effects of exercise in both skeletal muscle (59) and adipose (60), and our analysis of the effects in liver will be forthcoming.

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