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Insulin and insulin-like growth factor 1 antagonize the stimulation of ob gene expression by dexamethasone in cultured rat adipose tissue.
Biochem J. 1997 Jun 01; 324 (Pt 2):605-10.BJ

Abstract

The ob gene, specifically expressed in fat cells, encodes leptin, a hormone that induces satiety and increases energy expenditure. In this study, we investigated the interactions between glucocorticoids and insulin on ob gene expression in cultured explants of rat adipose tissue. Only low levels of ob mRNA were detected when adipose tissue from fasted rats was cultured for 12-24 h in minimal essential medium. However, the addition of dexamethasone to the medium increased ob gene expression in a concentration-dependent manner (EC50 10 nM). With 1 microM dexamethasone, ob mRNA levels were similar to those in fresh fat pads from fed rats, reaching a maximum after 12 h. The effect of dexamethasone was blocked by actinomycin D, which indicates an action on transcription. This effect was increased when a minimum amount of fuel (glucose or a mixture of lactate and pyruvate) was supplied in the medium. Unlike dexamethasone, insulin, even when combined with high glucose concentrations, did not induce ob expression, although it strongly increased the accumulation of mRNA species for fatty acid synthase (FAS), the insulin-sensitive glucose transporter GLUT4 and the gamma isoform of peroxisome proliferator-activated receptor (PPARgamma). Unexpectedly, insulin dose-dependently inhibited dexamethasone-induced ob mRNA accumulation. This effect was observed at low concentrations of insulin (IC50 1 nM) and was delayed in onset, beginning after 6-9 h of culture. It was mimicked by insulin-like growth factor 1 (IGF-1) (100 nM). The inhibition by insulin was only detectable when fuels were present and/or when a critical level of ob expression was reached. As this inhibitory effect was reversed by cycloheximide, this suggests that it required ongoing protein synthesis. In conclusion, unlike dexamethasone, insulin had no direct stimulatory effect on ob gene expression. On the other hand, insulin (and IGF-1) even inhibited the dexamethasone-induced accumulation of ob mRNA. The underlying mechanism involved ongoing synthesis of an inhibitory protein by insulin, which is in keeping with its delayed effect. Moreover, the expression of genes for FAS, GLUT4 and PPARgamma may be inversely related to that of ob.

Authors+Show Affiliations

Endocrinology and Metabolism Unit, University of Louvain, Faculty of Medicine, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9182724

Citation

Reul, B A., et al. "Insulin and Insulin-like Growth Factor 1 Antagonize the Stimulation of Ob Gene Expression By Dexamethasone in Cultured Rat Adipose Tissue." The Biochemical Journal, vol. 324 (Pt 2), 1997, pp. 605-10.
Reul BA, Ongemba LN, Pottier AM, et al. Insulin and insulin-like growth factor 1 antagonize the stimulation of ob gene expression by dexamethasone in cultured rat adipose tissue. Biochem J. 1997;324 (Pt 2):605-10.
Reul, B. A., Ongemba, L. N., Pottier, A. M., Henquin, J. C., & Brichard, S. M. (1997). Insulin and insulin-like growth factor 1 antagonize the stimulation of ob gene expression by dexamethasone in cultured rat adipose tissue. The Biochemical Journal, 324 (Pt 2), 605-10.
Reul BA, et al. Insulin and Insulin-like Growth Factor 1 Antagonize the Stimulation of Ob Gene Expression By Dexamethasone in Cultured Rat Adipose Tissue. Biochem J. 1997 Jun 1;324 (Pt 2):605-10. PubMed PMID: 9182724.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin and insulin-like growth factor 1 antagonize the stimulation of ob gene expression by dexamethasone in cultured rat adipose tissue. AU - Reul,B A, AU - Ongemba,L N, AU - Pottier,A M, AU - Henquin,J C, AU - Brichard,S M, PY - 1997/6/1/pubmed PY - 1997/6/1/medline PY - 1997/6/1/entrez SP - 605 EP - 10 JF - The Biochemical journal JO - Biochem. J. VL - 324 (Pt 2) N2 - The ob gene, specifically expressed in fat cells, encodes leptin, a hormone that induces satiety and increases energy expenditure. In this study, we investigated the interactions between glucocorticoids and insulin on ob gene expression in cultured explants of rat adipose tissue. Only low levels of ob mRNA were detected when adipose tissue from fasted rats was cultured for 12-24 h in minimal essential medium. However, the addition of dexamethasone to the medium increased ob gene expression in a concentration-dependent manner (EC50 10 nM). With 1 microM dexamethasone, ob mRNA levels were similar to those in fresh fat pads from fed rats, reaching a maximum after 12 h. The effect of dexamethasone was blocked by actinomycin D, which indicates an action on transcription. This effect was increased when a minimum amount of fuel (glucose or a mixture of lactate and pyruvate) was supplied in the medium. Unlike dexamethasone, insulin, even when combined with high glucose concentrations, did not induce ob expression, although it strongly increased the accumulation of mRNA species for fatty acid synthase (FAS), the insulin-sensitive glucose transporter GLUT4 and the gamma isoform of peroxisome proliferator-activated receptor (PPARgamma). Unexpectedly, insulin dose-dependently inhibited dexamethasone-induced ob mRNA accumulation. This effect was observed at low concentrations of insulin (IC50 1 nM) and was delayed in onset, beginning after 6-9 h of culture. It was mimicked by insulin-like growth factor 1 (IGF-1) (100 nM). The inhibition by insulin was only detectable when fuels were present and/or when a critical level of ob expression was reached. As this inhibitory effect was reversed by cycloheximide, this suggests that it required ongoing protein synthesis. In conclusion, unlike dexamethasone, insulin had no direct stimulatory effect on ob gene expression. On the other hand, insulin (and IGF-1) even inhibited the dexamethasone-induced accumulation of ob mRNA. The underlying mechanism involved ongoing synthesis of an inhibitory protein by insulin, which is in keeping with its delayed effect. Moreover, the expression of genes for FAS, GLUT4 and PPARgamma may be inversely related to that of ob. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/9182724/Insulin_and_insulin_like_growth_factor_1_antagonize_the_stimulation_of_ob_gene_expression_by_dexamethasone_in_cultured_rat_adipose_tissue_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/bj3240605 DB - PRIME DP - Unbound Medicine ER -