Proteomic Analysis of 3T3-L1 Adipocytes Treated with Insulin and TNF-α.
Hayley ChanKetaki P BhideAditya VaidyamVictoria HedrickTiago Jose Paschoal SobreiraThomas G SorsRyan W GrantUma K AryalPublished in: Proteomes (2019)
Insulin resistance is an indication of early stage Type 2 diabetes (T2D). Insulin resistant adipose tissues contain higher levels of insulin than the physiological level, as well as higher amounts of intracellular tumor necrosis factor-α (TNF-α) and other cytokines. However, the mechanism of insulin resistance remains poorly understood. To better understand the roles played by insulin and TNF-α in insulin resistance, we performed proteomic analysis of differentiated 3T3-L1 adipocytes treated with insulin (Ins), TNF-α (TNF), and both (Ins + TNF). Out of the 693 proteins identified, the abundances of 78 proteins were significantly different (p < 0.05). Carnitine parmitoyltransferase-2 (CPT2), acetyl CoA carboxylase 1 (ACCAC-1), ethylmalonyl CoA decarboxylase (ECHD1), and methylmalonyl CoA isomerase (MCEE), enzymes required for fatty acid β-oxidation and respiratory electron transport, and β-glucuronidase, an enzyme responsible for the breakdown of complex carbohydrates, were down-regulated in all the treatment groups, compared to the control group. In contrast, superoxide dismutase 2 (SOD2), protein disulfide isomerase (PDI), and glutathione reductase, which are the proteins responsible for cytoskeletal structure, protein folding, degradation, and oxidative stress responses, were up-regulated. This suggests higher oxidative stress in cells treated with Ins, TNF, or both. We proposed a conceptual metabolic pathway impacted by the treatments and their possible link to insulin resistance or T2D.
Keyphrases
- type diabetes
- insulin resistance
- rheumatoid arthritis
- glycemic control
- adipose tissue
- fatty acid
- early stage
- high fat diet induced
- metabolic syndrome
- oxidative stress
- cardiovascular disease
- polycystic ovary syndrome
- skeletal muscle
- magnetic resonance
- transcription factor
- squamous cell carcinoma
- radiation therapy
- dna damage
- computed tomography
- hydrogen peroxide
- cell death
- molecular dynamics simulations
- contrast enhanced
- cell proliferation
- replacement therapy
- heat shock
- heat shock protein