EMD: Diabetes and Obesity - Tumor Necrosis Factor-a and Obesity

		Technical Resources

		Technical Information

		Calbiochem Information

		Diabetes Resource

		Akt/PKB Signaling
		PI 3-K Signaling
		AMPK
		mTOR
		Protein Tyrosine Phosphatases
		GSK-3
		Lipids
		Sphingomyelinase
		HMG-CoA
		PPAR
		Phosphodiesterases
		Glucose Transporters
		Insulin like Growth factors
		IGF Receptor
		Insulin Mimetics
		JAK/STAT
		Tumor Necrosis Factor
		Inhibitors of Mitochondrial Function
		Sirtuins and Leptin
		Orexins, Resistin, Peptides, C-Reactive
		Other products of interest

Diabetes and Obesity: Tumor Necrosis Fator-a and Obesity

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A number of studies have established a relationship between obesity, insulin resistance, and dyslipidemia. It has been shown that TNF-a is a mediator of insulin resistance in obesity and is over-expressed in adipose tissue of obese rodents and humans. Rodents with genetic obesity and insulin resistance express about 5- to10-fold more TNF-a mRNA, and twice as much TNF-a in their adipose tissue. Elevated levels of TNF-a are shown to down-regulate tyrosine kinase activity of the insulin receptor and diminish the expression of GLUT-4 glucose transporters in obese subjects.

TNF-a elicits its cellular responses via two receptors, TNFR1 (p55) and TNFR2 (p75), which are expressed in relatively different amounts in all mammalian cells. Activation of p55 results in impaired insulin-mediated glucose uptake. However, production of p75, but not p55, is shown to be higher in adipose tissue from human obese subjects. Hence, both receptors appear to be essential for normal glucose homeostasis. Obese (ob/ob) mice deficient in both p55 and p75 receptors exhibit an improvement in fasting plasma glucose levels and a reduction in circulating insulin levels when compared to ob/ob mice expressing these receptors. Diet induced weight loss reduces the expression of TNF-a and improves insulin sensitivity of tissues.

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Antibodies

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Inhibitors/Antagonists

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Proteins

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