Gene expression profile in obesity and type 2 diabetes mellitus

Abstract

Obesity is an important component of metabolic syndrome X and predisposes to the development of type 2 diabetes mellitus. The incidence of obesity, type 2 diabetes mellitus and metabolic syndrome X is increasing, and the cause(s) for this increasing incidence is not clear. Although genetics could play an important role in the higher prevalence of these diseases, it is not clear how genetic factors interact with environmental and dietary factors to increase their incidence. We performed gene expression profile in subjects with obesity and type 2 diabetes mellitus with and without family history of these diseases. It was noted that genes involved in carbohydrate, lipid and amino acid metabolism pathways, glycan of biosynthesis, metabolism of cofactors and vitamin pathways, ubiquitin mediated proteolysis, signal transduction pathways, neuroactive ligandreceptor interaction, nervous system pathways, neurodegenerative disorders pathways are upregulated in obesity compared to healthy subjects. In contrast genes involved in cell adhesion molecules, cytokine-cytokine receptor interaction, insulin signaling and immune system pathways are downregulated in obese. Genes involved in signal transduction, regulation of actin cytoskeleton, antigen processing and presentation, complement and coagulation cascades, axon guidance and neurodegenerative disorders pathways are upregulated in subjects with type 2 diabetes with family history of diabetes compared to those who are diabetic but with no family history. Genes involved in oxidative phosphorylation, immune, nervous system, and metabolic disorders pathways are upregulated in those with diabetes with family history of diabetes compared to those with diabetes but with no family history. In contrast, genes involved in lipid and amino acid pathways, ubiquitin mediated proteolysis, signal transduction, insulin signaling and PPAR signaling pathways are downregulated in subjects with diabetes with family history of diabetes. It was noted that genes involved in inflammatory pathway are differentially expressed both in obesity and type 2 diabetes. These results suggest that genes concerned with carbohydrate, lipid and amino acid metabolic pathways, neuronal function and inflammation play a significant role in the pathobiology of obesity and type 2 diabetes.

FTO mRNA Expression in Extremely Obese and Type 2 Diabetic Human Omental and Subcutaneous Adipose Tissues

“…Genes involved in inflammatory pathway are known to be differentially expressed both in obesity and T2DM which suggests the idea of genes concerned with carbohydrate, lipid and amino acid metabolic pathways, neuronal function, and inflammation play important roles in the pathobiology of obesity and T2DM [34]. A limited number of studies have explored the mRNA expression levels and thus the biological function of FTO in human adipose tissues.…”

Proteomic changes associated with diabetes in the BB-DP rat

“…Since no gene expression screen has been conducted on the BB-DP rat, a direct comparison between the proteomic data and screens is difficult. It is interesting to note that many of the screen studies in diabetic models (13,15,64) did not detect gene expression changes in many genes that have been found to be altered in focused studies on similar diabetic models (for example, see Ref. 45).…”

Synergy of BMI and family history on diabetes: the Humboldt Study

“…Family history of type 2 diabetes is associated with decreased insulin sensitivity and an impaired balance between insulin sensitivity and insulin secretion (8) . A number of genes have been identified to be associated with type 2 diabetes (9)(10)(11) . The prevalence of type 2 diabetes is predicted to increase to epidemic proportions in the coming decades, primarily due to lifestyle changes (12) .…”