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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

Energy balance across the estrous cycle and following OVX in lean and obese rats. Energy balance (intake – expenditure) was measured in lean and obese rats during each phase of the estrous cycle [diestrus 1 (D1), diestrus 2 (D2), proestrus (P), and estrus (E)], immediately following surgical ovariectomy (OVX) while in energy balance (OVX-EB), and during OVX-induced rapid weight gain (OVX-Gain). Relative circulating estrogen levels across the cycle (D1–E) and corresponding follicular and luteal phases of the human menstrual cycle are indicated. Obese rats experience greater fluctuations in energy balance across the cycle compared to lean rats. A rise in circulating estrogens is associated with a decrease in food intake (and energy balance) in the lean; however, this response is delayed in the obese. *Significant difference between lean and obese groups (P < 0.05). Modified from Ref. (40).
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Figure 3: Energy balance across the estrous cycle and following OVX in lean and obese rats. Energy balance (intake – expenditure) was measured in lean and obese rats during each phase of the estrous cycle [diestrus 1 (D1), diestrus 2 (D2), proestrus (P), and estrus (E)], immediately following surgical ovariectomy (OVX) while in energy balance (OVX-EB), and during OVX-induced rapid weight gain (OVX-Gain). Relative circulating estrogen levels across the cycle (D1–E) and corresponding follicular and luteal phases of the human menstrual cycle are indicated. Obese rats experience greater fluctuations in energy balance across the cycle compared to lean rats. A rise in circulating estrogens is associated with a decrease in food intake (and energy balance) in the lean; however, this response is delayed in the obese. *Significant difference between lean and obese groups (P < 0.05). Modified from Ref. (40).

Mentions: Aside from the initial studies that showed no difference in EI, TEE, or activity levels between DIO and DR rats, our work with the female-specific aspect of this model has not specifically addressed the differences between male and female rats in terms of their propensity to become obese. We have, however, performed comprehensive metabolic studies of the mature lean and obese animals across the estrous cycle, and during the initial stages of weight gain following surgical OVX (40). We observed that obese animals experienced greater fluctuations in energy balance across the 4-day estrous cycle than their lean counterparts, and this was driven by greater variability in food intake across the cycle (Figure 3). A rise in estrogen levels during the proestrus phase of the cycle underlies a reduction in food intake, and this estrogen-mediated response appears to be delayed in obese animals (Figure 3). While circulating estradiol levels were not significantly different between the DIO and DR animals, we suspect that the inherent impairment in leptin and/or insulin sensitivity in the obese may impart reduced sensitivity to the effects of estrogen at this stage of their cycle. Additional studies are needed to examine this possibility. We further found that cycling obese rats were less active, expended more energy per movement, and oxidized more carbohydrate than lean rats. Despite these phenotypic differences across the cycle, OVX induced a large positive energy imbalance in both obese and lean rats, which resulted primarily from an increase in energy intake in both groups. TEE was not altered in either group, despite the fact that they were eating more food. Our interpretation of these observations is that the increased thermic effect of food (from the greater food intake) is essentially balanced out by any reduction in the non-resting energy expenditure (NREE) that occurs from the decline in physical activity levels.


Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females
Energy balance across the estrous cycle and following OVX in lean and obese rats. Energy balance (intake – expenditure) was measured in lean and obese rats during each phase of the estrous cycle [diestrus 1 (D1), diestrus 2 (D2), proestrus (P), and estrus (E)], immediately following surgical ovariectomy (OVX) while in energy balance (OVX-EB), and during OVX-induced rapid weight gain (OVX-Gain). Relative circulating estrogen levels across the cycle (D1–E) and corresponding follicular and luteal phases of the human menstrual cycle are indicated. Obese rats experience greater fluctuations in energy balance across the cycle compared to lean rats. A rise in circulating estrogens is associated with a decrease in food intake (and energy balance) in the lean; however, this response is delayed in the obese. *Significant difference between lean and obese groups (P < 0.05). Modified from Ref. (40).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 3: Energy balance across the estrous cycle and following OVX in lean and obese rats. Energy balance (intake – expenditure) was measured in lean and obese rats during each phase of the estrous cycle [diestrus 1 (D1), diestrus 2 (D2), proestrus (P), and estrus (E)], immediately following surgical ovariectomy (OVX) while in energy balance (OVX-EB), and during OVX-induced rapid weight gain (OVX-Gain). Relative circulating estrogen levels across the cycle (D1–E) and corresponding follicular and luteal phases of the human menstrual cycle are indicated. Obese rats experience greater fluctuations in energy balance across the cycle compared to lean rats. A rise in circulating estrogens is associated with a decrease in food intake (and energy balance) in the lean; however, this response is delayed in the obese. *Significant difference between lean and obese groups (P < 0.05). Modified from Ref. (40).
Mentions: Aside from the initial studies that showed no difference in EI, TEE, or activity levels between DIO and DR rats, our work with the female-specific aspect of this model has not specifically addressed the differences between male and female rats in terms of their propensity to become obese. We have, however, performed comprehensive metabolic studies of the mature lean and obese animals across the estrous cycle, and during the initial stages of weight gain following surgical OVX (40). We observed that obese animals experienced greater fluctuations in energy balance across the 4-day estrous cycle than their lean counterparts, and this was driven by greater variability in food intake across the cycle (Figure 3). A rise in estrogen levels during the proestrus phase of the cycle underlies a reduction in food intake, and this estrogen-mediated response appears to be delayed in obese animals (Figure 3). While circulating estradiol levels were not significantly different between the DIO and DR animals, we suspect that the inherent impairment in leptin and/or insulin sensitivity in the obese may impart reduced sensitivity to the effects of estrogen at this stage of their cycle. Additional studies are needed to examine this possibility. We further found that cycling obese rats were less active, expended more energy per movement, and oxidized more carbohydrate than lean rats. Despite these phenotypic differences across the cycle, OVX induced a large positive energy imbalance in both obese and lean rats, which resulted primarily from an increase in energy intake in both groups. TEE was not altered in either group, despite the fact that they were eating more food. Our interpretation of these observations is that the increased thermic effect of food (from the greater food intake) is essentially balanced out by any reduction in the non-resting energy expenditure (NREE) that occurs from the decline in physical activity levels.

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