Progress 10/01/08 to 09/30/09
Outputs
OUTPUTS: The last two decades have seen a dramatic increase in the prevalence of obesity worldwide, and the medical conditions associated with obesity now constitute a huge burden on public health. One of the aims of the current proposal is to determine whether aging increases susceptibility to diet-induced obesity and whether the sex differences found in young rats, disappears in middle-age rats. Middle-aged male and female rats were maintained on either a chow (LF) diet or high- fat (HF) diet. After 3 weeks on the diets, animals with indwelling intra-third-cerebral ventricle (i3vt) cannulas were centrally injected with leptin. The third cerebral ventricle gives access to the hypothalamus of the brain, the area implicated in the control of food intake and body weight. Leptin, a hormone secreted by fat cells, circulates in the plasma in direct proportion to adiposity. A dose-response curve is being generated for each group allowing us to determine leptin sensitivity over a range of doses in order to make a better comparison to published data on young (3 month old) male and female rats. Preliminary results obtained during this reporting period indicate that middle-aged female rats gain weight on a diet high in saturated fat (butter fat) at levels similar to age-matched males. In unpublished data collected with my collaborators at the University of Cincinnati's Obesity Research Center, we found that young female rats are resistant to weight gain when given a high-fat (HF) diet; female rats simply eat less whereas male rats overeat when given a HF diet. Preliminary data using middle-aged male and female rats given a low-fat (LF) or HF diet for 2 weeks are promising. Male and female rats on LF diet ate comparable amounts and gained the same amount of weight (approx 5 g body weight (BW) gained; food intake (FI) approx 20 g/day). Surprisingly, on a HF diet they were comparable as well (50 g BW gained; FI 30 g/day). These very preliminary data suggest that middle-aged females may be more susceptible to weight gain on a HF diet than young female rats. In addition, these data suggest that using rats that are middle-aged (9 months old) may be a good starting point to examine when sex differences in the regulation of body weight and food intake start to disappear in rats. In addition, the effective dose of leptin for middle-aged rats is higher than that reported for young rats. Preliminary results indicate that middle-aged females reduce food intake and body weight when given an i3vt 7.5 micrograms/microliter leptin injection. This is considerably higher than the published dose for young females (i3vt 3.5 micrograms/microliter leptin; 2006 Diabetes Clegg, Brown et al.). This was done so that I the considerable historical data on younger animals that my collaborators in Cincinnati have collected could be used for comparison. In the coming year we will focus on increasing the number of rats and the analysis of body composition, plasma and hypothalamic genes for this study. Results thus far suggest that aged rats are more susceptible to diet-induced obesity and that one possible mechanism for this change is central leptin resistance. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
It is well established that as humans and animals age, many get fatter and develop insulin and leptin resistance, making them more susceptible to acquiring the metabolic syndrome. In addition, an increased availability and consumption of high-fat foods increases the risk of the metabolic syndrome. Women entering menopause increase their visceral fat and are at increased risk of developing the metabolic syndrome with aging. The objective of this grant is to test the hypothesis that aging female rats will accrue fat in the visceral depot and become leptin resistant due to declining estrogen values. This has human relevance as it mimics the perimenopausal state, and will begin to provide a mechanism by which perimenopausal women are more prone to the diseases associated with the metabolic syndrome.
Publications
- No publications reported this period
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Progress 10/01/07 to 09/30/08
Outputs
OUTPUTS: The last two decades have seen a dramatic increase in the prevalence of obesity worldwide, and the medical conditions associated with obesity now constitute a huge burden on public health. One of the aims of the current proposal is to determine whether aging increases susceptibility to diet-induced obesity and whether the sex differences found in young rats, disappears in middle-age rats. Middle-aged male and female rats were maintained on either a chow (LF) diet or high- fat (HF) diet. After 3 weeks on the diets, animals with indwelling intra-third-cerebral ventricle (i3vt) cannulas were centrally injected with leptin. The third cerebral ventricle gives access to the hypothalamus of the brain, the area implicated in the control of food intake and body weight. Leptin, a hormone secreted by fat cells, circulates in the plasma in direct proportion to adiposity. A dose-response curve is being generated for each group allowing us to determine leptin sensitivity over a range of doses in order to make a better comparison to published data on young (3 month old) male and female rats. Preliminary results obtained during this reporting period indicate that middle-aged female rats gain weight on a diet high in saturated fat (butter fat) at levels similar to age-matched males. In unpublished data collected with my collaborators at the University of Cincinnati's Obesity Research Center, we found that young female rats are resistant to weight gain when given a high-fat (HF) diet; female rats simply eat less whereas male rats overeat when given a HF diet. Preliminary data using middle-aged male and female rats given a low-fat (LF) or HF diet for 2 weeks are promising. Male and female rats on LF diet ate comparable amounts and gained the same amount of weight (approx 5 g body weight (BW) gained; food intake (FI) approx 20 g/day). Surprisingly, on a HF diet they were comparable as well (50 g BW gained; FI 30 g/day). These very preliminary data suggest that middle-aged females may be more susceptible to weight gain on a HF diet than young female rats. In addition, these data suggest that using rats that are middle-aged (9 months old) may be a good starting point to examine when sex differences in the regulation of body weight and food intake start to disappear in rats. In addition, the effective dose of leptin for middle-aged rats is higher than that reported for young rats. Preliminary results indicate that middle-aged females reduce food intake and body weight when given an i3vt 7.5 micrograms/microliter leptin injection. This is considerably higher than the published dose for young females (i3vt 3.5 micrograms/microliter leptin; 2006 Diabetes Clegg, Brown et al.). This was done so that I the considerable historical data on younger animals that my collaborators in Cincinnati have collected could be used for comparison. In the coming year we will focus on increasing the number of rats and the analysis of body composition, plasma and hypothalamic genes for this study. Results thus far suggest that aged rats are more susceptible to diet-induced obesity and that one possible mechanism for this change is central leptin resistance. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
It is well established that as humans and animals age, many get fatter and develop insulin and leptin resistance, making them more susceptible to acquiring the metabolic syndrome. In addition, an increased availability and consumption of high-fat foods increases the risk of the metabolic syndrome. Women entering menopause increase their visceral fat and are at increased risk of developing the metabolic syndrome with aging. The objective of this grant is to test the hypothesis that aging female rats will accrue fat in the visceral depot and become leptin resistant due to declining estrogen values. This has human relevance as it mimics the perimenopausal state, and will begin to provide a mechanism by which perimenopausal women are more prone to the diseases associated with the metabolic syndrome.
Publications
- No publications reported this period
|
Progress 10/01/06 to 09/30/07
Outputs
The last two decades have seen a dramatic increase in the prevalence of obesity worldwide, and the medical conditions associated with obesity now constitute a huge burden on public health. One of the aims of the current proposal is to determine whether aging increases susceptibility to diet-induced obesity and whether the sex differences found in young rats, disappears in middle-age rats. Middle-aged male and female rats were maintained on either a chow (LF) diet or high- fat (HF) diet. After 3 weeks on the diets, animals with indwelling intra-third-cerebral ventricle (i3vt) cannulas were centrally injected with leptin. The third cerebral ventricle gives access to the hypothalamus of the brain, the area implicated in the control of food intake and body weight. Leptin, a hormone secreted by fat cells, circulates in the plasma in direct proportion to adiposity. A dose-response curve is being generated for each group allowing us to determine leptin sensitivity over a
range of doses in order to make a better comparison to published data on young (3 month old) male and female rats. Preliminary results obtained during this reporting period indicate that middle-aged female rats gain weight on a diet high in saturated fat (butter fat) at levels similar to age-matched males. In unpublished data collected with my collaborators at the University of Cincinnati's Obesity Research Center, we found that young female rats are resistant to weight gain when given a high-fat (HF) diet; female rats simply eat less whereas male rats overeat when given a HF diet. Preliminary data using middle-aged male and female rats given a low-fat (LF) or HF diet for 2 weeks are promising. Male and female rats on LF diet ate comparable amounts and gained the same amount of weight (approx 5 g body weight (BW) gained; food intake (FI) approx 20 g/day). Surprisingly, on a HF diet they were comparable as well (50 g BW gained; FI 30 g/day). These very preliminary data suggest that
middle-aged females may be more susceptible to weight gain on a HF diet than young female rats. In addition, these data suggest that using rats that are middle-aged (9 months old) may be a good starting point to examine when sex differences in the regulation of body weight and food intake start to disappear in rats. In addition, the effective dose of leptin for middle-aged rats is higher than that reported for young rats. Preliminary results indicate that middle-aged females reduce food intake and body weight when given an i3vt 7.5 micrograms/microliter leptin injection. This is considerably higher than the published dose for young females (i3vt 3.5 micrograms/microliter leptin; 2006 Diabetes Clegg, Brown et al.). This was done so that the considerable historical data on younger animals that my collaborators in Cincinnati have collected could be used for comparison. In the coming year we will focus on increasing the number of rats and the analysis of body composition, plasma and
hypothalamic genes for this study. Results thus far suggest that aged rats are more susceptible to diet-induced obesity and that one possible mechanism for this change is central leptin resistance.
Impacts
It is well established that as humans and animals age, many get fatter and develop insulin and leptin resistance, making them more susceptible to acquiring the metabolic syndrome. In addition, an increased availability and consumption of high-fat foods increases the risk of the metabolic syndrome. Women entering menopause increase their visceral fat and are at increased risk of developing the metabolic syndrome with aging. The objective of this grant is to test the hypothesis that aging female rats will accrue fat in the visceral depot and become leptin resistant due to declining estrogen values. This has human relevance as it mimics the perimenopausal state, and will begin to provide a mechanism by which perimenopausal women are more prone to the diseases associated with the metabolic syndrome.
Publications
- No publications reported this period
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