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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.

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HbA1c in whole blood.Percentages of glycosylated hemoglobin (HbA1c) as a function of age in blood of GK and WKY rats. Data represent means and error bars 1 SD of the mean. Closed circles = GK; open circles = WKY). * = P<0.05; ** = P<0.001.
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pone-0017386-g004: HbA1c in whole blood.Percentages of glycosylated hemoglobin (HbA1c) as a function of age in blood of GK and WKY rats. Data represent means and error bars 1 SD of the mean. Closed circles = GK; open circles = WKY). * = P<0.05; ** = P<0.001.

Mentions: Plasma glucose measurements in these animals have been previously published [16], but are available here in Figure S1. As early as 4 weeks of age, plasma glucose was significantly higher in GK animals and continued to increase until it reached a plateau at 12 weeks between 500 and 600 mg/dl. To augment those previously reported measurements, we additionally measured glycosylated hemoglobin. Consistent with the hyperglycemic profile measured at the time of sacrifice in the GK group was a continuous increase in HbA1c throughout the experimental period, from a low baseline reading of 4% or less (LLD = 4%) to over 11% at 20 weeks (Figure 4).


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)

HbA1c in whole blood.Percentages of glycosylated hemoglobin (HbA1c) as a function of age in blood of GK and WKY rats. 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-g004: HbA1c in whole blood.Percentages of glycosylated hemoglobin (HbA1c) as a function of age in blood of GK and WKY rats. Data represent means and error bars 1 SD of the mean. Closed circles = GK; open circles = WKY). * = P<0.05; ** = P<0.001.
Mentions: Plasma glucose measurements in these animals have been previously published [16], but are available here in Figure S1. As early as 4 weeks of age, plasma glucose was significantly higher in GK animals and continued to increase until it reached a plateau at 12 weeks between 500 and 600 mg/dl. To augment those previously reported measurements, we additionally measured glycosylated hemoglobin. Consistent with the hyperglycemic profile measured at the time of sacrifice in the GK group was a continuous increase in HbA1c throughout the experimental period, from a low baseline reading of 4% or less (LLD = 4%) to over 11% at 20 weeks (Figure 4).

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