The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo.
Inflammatory cytokines have been linked to obesity-related insulin resistance. To investigate the effect of TNF-alpha, an inflammatory cytokine, on insulin action, C57BL/6J mice were treated with TNF-alpha for 7 days after which we examined the in vivo effects of TNF-alpha on glucose tolerance and insulin sensitivity with IV glucose tolerance tests and hyperinsulinemic-euglycemic clamps. In addition, we analyzed the in vivo effect of TNF-alpha on several metabolism-related genes and adipocytokines implicated in the development of insulin resistance. TNF-alpha treatment resulted in markedly increased fasting blood glucose, insulin and free fatty acids (FFA) levels and reduced glucose tolerance. During the clamps, the rates insulin-stimulated whole body (G(Rd)) and skeletal muscle glucose uptake (MGU) and insulin's ability to suppress hepatic glucose production (HGP) were decreased in TNF-alpha treated animals, indicating insulin resistance. In addition, both PPARgamma and ATGL mRNA expression in adipose tissues as well as ATGL protein levels in plasma were downregulated. Moreover, adipose mRNA expression and plasma protein levels of adiponectin and visfatin were significantly down-regulated. We conclude that the alterations of PPARgamma, ATGL, adiponectin and visfatin may contribute to the development of insulin resistance mediated by TNF-alpha.
Li
Ling
L
The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education, Department of Clinical Biochemistry, Chongqing Medical University, 400016 Chongqing, China. lingli31@yahoo.com.cn
Yang
Gangyi
G
Shi
Shaochuan
S
Yang
Mengliu
M
Liu
Hua
H
Boden
Guenther
G
D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008049:Lipase; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases
D000214:Acyl Coenzyme A; D052242:Adiponectin; D001786:Blood Glucose; D002265:Carboxylic Ester Hydrolases; D002334:Carnitine O-Palmitoyltransferase; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D005947:Glucose; D007328:Insulin; D008049:Lipase; D054409:Nicotinamide Phosphoribosyltransferase; D047495:PPAR gamma; D011973:Receptors, LDL; D002787:Sterol Esterase; D051782:Sterol Regulatory Element Binding Protein 2; D014409:Tumor Necrosis Factor-alpha; C497391:Srebf2 protein, mouse; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; C495867:nicotinamide phosphoribosyltransferase, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases