Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells.

Ohsumi, Jun; Sakakibara, Satoshi; Yamaguchi, Junna; Miyadai, Kenji; Yoshioka, Shinji; Fujiwara, Toshihiko; Horikoshi, Hiroyoshi; Serizawa, Nobufusa

doi:10.1210/endo.135.5.7956951

Cited by 82 publications

(29 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, TZDs decrease TNF-␣ expression in adipocytes of obese animals (13). Moreover, TZDs reduce the antidifferentiation effect of TNF-␣ that is observed after long treatment of adipocytes with high concentrations of TNF-␣ (40,41). Here, we report that two TZDs (pioglitazone and troglitazone) interfere with the ability of TNF-␣ to inhibit the insulin receptor tyrosine kinase activity.…”

Section: Discussionmentioning

confidence: 82%

Thiazolidinediones block tumor necrosis factor-alpha-induced inhibition of insulin signaling.

Peraldi

Xu²,

Spiegelman³

1997

J. Clin. Invest.

289

149

View full text Add to dashboard Cite

TNF-␣ has been shown to be an important mediator of insulin resistance linked to obesity. This cytokine induces insulin resistance, at least in part, through inhibition of the tyrosine kinase activity of the insulin receptor. Recently, a new class of compounds, the antidiabetic thiazolidinediones (TZDs), has been shown to improve insulin resistance in obesity and non-insulin-dependent diabetes mellitus in both rodents and man. Here we show that TZDs have powerful effects on the ability of TNF-␣ to alter the most proximal steps of insulin signaling, including tyrosine phosphorylation of the insulin receptor and its major substrate, IRS-1, and activation of PI3-kinase. Troglitazone or pioglitazone essentially eliminate the reduction in tyrosine phosphorylation of IR and IRS-1 caused by TNF-␣ in fat cells, even at relatively high doses (25 ng/ml). That this effect of TZDs operates through activation of the nuclear receptor PPAR ␥ / RXR complex is shown by the fact that similar effects are observed with other PPAR ␥ /RXR ligands such as 15 deoxy ⌬ 12,14 PGJ2 and LG268. The TZDs do not inhibit all TNF-␣ signaling in that the transcription factor NF-kB is still induced well. These data indicate that TZDs can specifically block certain actions of TNF-␣ related to insulin resistance, suggesting that this block may contribute to their antidiabetic actions. (

show abstract

Section: Discussionmentioning

confidence: 82%

Thiazolidinediones block tumor necrosis factor-alpha-induced inhibition of insulin signaling.

Peraldi

Xu²,

Spiegelman³

1997

J. Clin. Invest.

289

149

View full text Add to dashboard Cite

show abstract

“…These suggested that the disappearance of gender difference in our study was not responsible for plasma testosterone level, but might for some other factors such as tumor necrosis factor-a and peroxisome proliferator-activated receptor-g, both of which are known to affect the regulation of plasma adiponectin and glucose metabolism. [33][34][35][36][37] Togo et al describes that serum adiponectin concentrations in patients with olanzapine were not the same as those in patients with risperidone. 26 The present study could not evaluate the effect of an individual drug on plasma adiponectin levels, because the patients were taking diverse antipsychotic drugs.…”

Section: Discussionmentioning

confidence: 99%

Gender differences in association of plasma adiponectin with obesity reflect resultant insulin resistance in non‐diabetic Japanese patients with schizophrenia

Matsuda

Tanioka

Yoshioka

et al. 2005

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

Adipose tissues poorly produce adiponectin in the population with increased body fat mass and diabetes mellitus. It was investigated whether hypoadiponectinemia is associated with obesity and insulin resistance in patients with chronically medicated schizophrenia. A cross-sectional study was designed for 73 non-diabetic Japanese patients with schizophrenia. The patients aged < 70 years with body mass index (BMI) ≥ 18.5 were selected. Anthropometrics and blood parameters including fat-derived cytokines were measured, and then the BMI and homeostasis model assessmentinsulin resistance (HOMA-IR) was calculated. The variables were compared between the nonobesity (BMI, 18.5-24.9) and obesity ( ≥ 25.0) groups, and between genders. Plasma adiponectin negatively correlated with BMI ( r = -0.554, P < 0.0003) and HOMA-IR ( r = -0.380, P = 0.007) in men, but not in women. The obesity group in men, as compared with the non-obesity group, showed significantly lower plasma adiponectin ( P = 0.008) and higher HOMA-IR ( P < 0.05), but not in women. Plasma leptin showed a significant positive correlation with BMI ( r = 0.604, P < 0.0001 in men; r = 0.763, P < 0.0001 in women) and HOMA-IR ( r = 0.618, P < 0.0001 in men; r = 0.679, P < 0.0001 in women). The mean plasma leptin in the obesity group was significantly higher than that in the non-obesity group ( P < 0.01 in men; P < 0.01 in women). In contrast to plasma leptin, plasma adiponectin showed gender difference in relation to BMI and HOMA-IR.

show abstract

“…A variety of cytokines have been found to suppress fat cell differentiation. TNF‐α, IL‐1, and many other pro‐inflammatory cytokines have this effect on most cultured pre‐adipocyte lines, and in fact can “de‐differentiate” already mature fat cells 29,30. Indeed, the suppression of adipocyte lipoprotein lipase was used to purify “cachectin,” which was then found to be identical to TNF‐α31 The precise molecular basis for these cytokine effects is still not known, though suppression of expression of several key transcriptional regulators of adipogenesis has been observed.…”

Section: Hormonal and Environmental Aspects Of Adipogenesismentioning

confidence: 99%

The Molecular Control of Adipogenesis, with Special Reference to Lymphatic Pathology

Rosen

2002

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Adipogenesis is the process by which mature fat cells are formed from pre-adipocytes. Adipogenesis has come under increasing scrutiny not only because the availability of reliable in vitro models makes it an attractive choice for developmental studies, but also because adipocytes are increasingly recognized as major players in a variety of physiological and pathophysiological states, such as obesity and type 2 diabetes. Adipocytes develop from mesenchymal stem cell precursors that are characterized by multipotency. Under the influence of various cues, these cells become committed to the adipocyte lineage. Further hormonal stimulation recruits these pre-adipocytes to accumulate lipid, express fat-specific markers, and become sensitive to the metabolic effects of insulin. A complex transcriptional cascade regulates this process, involving several distinct classes of transcription factor. In particular, the role of the nuclear hormone receptor PPARgamma will be discussed, along with bZip family members C/EBPalpha, C/EBPbeta, and C/EBPdelta. The relationship of adipose depots to the lymphatic system will also be discussed.

show abstract

Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells.

Cited by 82 publications

References 2 publications

Thiazolidinediones block tumor necrosis factor-alpha-induced inhibition of insulin signaling.

Thiazolidinediones block tumor necrosis factor-alpha-induced inhibition of insulin signaling.

Gender differences in association of plasma adiponectin with obesity reflect resultant insulin resistance in non‐diabetic Japanese patients with schizophrenia

The Molecular Control of Adipogenesis, with Special Reference to Lymphatic Pathology

Contact Info

Product

Resources

About