Adipose Tissue Deficiency and Chronic Inflammation in Diabetic Goto-Kakizaki Rats

• Published in: PloS one Vol. 6; no. 2; p. e17386
• Main Authors: Xue, Bai, Sukumaran, Siddharth, Nie, Jing, Jusko, William J., DuBois, Debra C., Almon, Richard R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.02.2011; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipogenesis; Adiponectin; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Age; Age Factors; Algorithms; Animal diseases; Animal models; Animal tissues; Animals; Atrophy; Bioaccumulation; Bioinformatics; Biological response modifiers; Biology; Blood; Blood glucose; Body fat; Body Weight - genetics; Body Weight - physiology; Chronic Disease; Corticosterone; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Disease control; DNA microarrays; Drinking water; Endocrine system; Endocrinology; Famine; Food consumption; Gene expression; Gene Expression Profiling; Genes; Genotype & phenotype; Glycosylated hemoglobin; Growth and Development - physiology; Hyperglycemia; Immunity; Inflammation; Inflammation - complications; Inflammation - genetics; Inflammation - pathology; Insulin; Insulin resistance; Interferon; Leptin; Leukocytes; Life sciences; Lipogenesis; Major histocompatibility complex; Male; Medicine; Melatonin; Metabolism; Microarray Analysis; Neuropeptides; Obesity; Organ Size - genetics; Organ Size - physiology; Pharmaceutical sciences; Physiological aspects; Physiology; Rats; Rats, Inbred WKY; Rodents; Stat3 protein; Studies; Subgroups; Systems analysis; Time series; Toxicology; Triglycerides; Type 2 diabetes; White blood cell count; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017386

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.