Limits...
Adipose tissue deficiency and chronic inflammation in diabetic Goto-Kakizaki rats.

Xue B, Sukumaran S, Nie J, Jusko WJ, Dubois DC, Almon RR - PLoS ONE (2011)

Bottom Line: Systemic inflammation was reflected by chronically elevated white blood cell counts.Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes.This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.

ABSTRACT
Type 2 diabetes (T2DM) is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK) rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals.

Show MeSH

Related in: MedlinePlus

Body weights and food consumption.A) Body weight (grams) at sacrifice B) Daily food consumption (mg) adjusted for body weight (grams). Data represent means and error bars 1 SD of the mean. Closed circles = GK; open circles = WKY). * = P<0.05; ** = P<0.001.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3045458&req=5

pone-0017386-g002: Body weights and food consumption.A) Body weight (grams) at sacrifice B) Daily food consumption (mg) adjusted for body weight (grams). Data represent means and error bars 1 SD of the mean. Closed circles = GK; open circles = WKY). * = P<0.05; ** = P<0.001.

Mentions: Body weights at sacrifice and food consumption throughout the study are presented in Figure 2. Although there was no difference in body weights between the two groups of animals at 4 weeks of age, WKY were significantly heavier than GK animals by 8 weeks and this difference increased through the experimental period. Until about 14 weeks of age, total grams of food consumed per day were similar among both groups and then slightly decreased in WKY. However, when food consumption was adjusted for body weight (Figure 2), GK animals actually consumed significantly more food than WKYs from 8 weeks on. Figure 3A shows the weight of abdominal fat in both groups of animals. The weight of the fat pads in WKYs increased linearly with age, while the abdominal fat pads in the GK population stopped increasing in weight between 8 and 12 weeks with a slight decline suggested after 16 weeks. The epididymal fat pad showed a similar pattern (Figure 3B). The same data expressed as a percentage of body weight show that as the animals get older adipose tissue is a greater percentage of total body weight in control WKY but not in GK animals (Figures 3C and D). This is in distinct contrast to the results obtained with the livers from these animals. Although the livers from the WKY were somewhat larger, GKs livers were a significantly larger percent of body weight from 8 weeks until the end of the experiment.


Adipose tissue deficiency and chronic inflammation in diabetic Goto-Kakizaki rats.

Xue B, Sukumaran S, Nie J, Jusko WJ, Dubois DC, Almon RR - PLoS ONE (2011)

Body weights and food consumption.A) Body weight (grams) at sacrifice B) Daily food consumption (mg) adjusted for body weight (grams). Data represent means and error bars 1 SD of the mean. Closed circles = GK; open circles = WKY). * = P<0.05; ** = P<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045458&req=5

pone-0017386-g002: Body weights and food consumption.A) Body weight (grams) at sacrifice B) Daily food consumption (mg) adjusted for body weight (grams). Data represent means and error bars 1 SD of the mean. Closed circles = GK; open circles = WKY). * = P<0.05; ** = P<0.001.
Mentions: Body weights at sacrifice and food consumption throughout the study are presented in Figure 2. Although there was no difference in body weights between the two groups of animals at 4 weeks of age, WKY were significantly heavier than GK animals by 8 weeks and this difference increased through the experimental period. Until about 14 weeks of age, total grams of food consumed per day were similar among both groups and then slightly decreased in WKY. However, when food consumption was adjusted for body weight (Figure 2), GK animals actually consumed significantly more food than WKYs from 8 weeks on. Figure 3A shows the weight of abdominal fat in both groups of animals. The weight of the fat pads in WKYs increased linearly with age, while the abdominal fat pads in the GK population stopped increasing in weight between 8 and 12 weeks with a slight decline suggested after 16 weeks. The epididymal fat pad showed a similar pattern (Figure 3B). The same data expressed as a percentage of body weight show that as the animals get older adipose tissue is a greater percentage of total body weight in control WKY but not in GK animals (Figures 3C and D). This is in distinct contrast to the results obtained with the livers from these animals. Although the livers from the WKY were somewhat larger, GKs livers were a significantly larger percent of body weight from 8 weeks until the end of the experiment.

Bottom Line: Systemic inflammation was reflected by chronically elevated white blood cell counts.Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes.This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.

ABSTRACT
Type 2 diabetes (T2DM) is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK) rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals.

Show MeSH
Related in: MedlinePlus