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Interferon-gamma and interleukin-1 beta inhibit adipoconversion in cultured rodent preadipocytes
F Grégoire1, N De Broux, N Hauser
1Laboratory of Cell Biology, Faculty of Sciences, University of Louvain, Belgium.
Abstract:
Cytokines like tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), and interleukin-1 (IL-1) are known to interfere with the differentiation of cultured cell lines of adipocyte precursors. In the present study, the effect of mouse and rat IFN-gamma, as well as human IL-1 beta, was investigated on rodent preadipocytes in primary cultures, either in the presence of fetal bovine serum (FBS, 10%) or in serum-free defined medium. IFN-gamma exerted an antiproliferative action that was more pronounced when cells reached confluency than during the growth phase of the culture. Morphological observation and quantifications of undifferentiated and differentiating cells revealed that IFN-gamma caused a decrease in the proportion of cells devoid of lipid droplets which would correspond to fibroblast-like cells, whereas preadipocytes remained unaffected. IFN-gamma induced a marked retardation of adipoconversion, resulting in a partial inhibition of lipoprotein lipase (LPL) activity and a severe decrease in glycerol-3-phosphate dehydrogenase (GPDH) activity. The antiproliferative and anti-LPL effects of IFN-gamma were neutralized by adding anti-IFN-gamma antibodies, while these antibodies prevented only partially the depressing effect of IFN-gamma on GPDH activity. Contrary to IFN-gamma, IL-1 beta slightly enhanced the proliferation in preadipocyte cultures. IL-1 beta also depressed adipoconversion, inhibited markedly LPL activity, and partially reduced GPDH activity. These results show that the influence of cytokines on adipoconversion observed in preadipocyte cell lines can be found in normal preadipocytes in culture.
Insights
Interferon-gamma (IFN-gamma) and interleukin-1 beta (IL-1 beta) inhibit adipocyte differentiation in rodent preadipocytes. These cytokines impair key enzymes and reduce fat cell formation, confirming in vitro findings in primary cultures.
Area of Science:
- Cell Biology
- Endocrinology
- Biochemistry
Background:
- Cytokines like TNF, IFN-gamma, and IL-1 are known to disrupt adipocyte precursor differentiation.
- Understanding cytokine effects on adipogenesis is crucial for metabolic research.
Purpose of the Study:
- To investigate the impact of mouse/rat IFN-gamma and human IL-1 beta on primary rodent preadipocyte differentiation.
- To compare cytokine effects in serum-containing and serum-free media.
Main Methods:
- Primary rodent preadipocyte cultures were used.
- Cells were treated with IFN-gamma or IL-1 beta in the presence or absence of fetal bovine serum.
- Assays included proliferation, morphology, lipid droplet quantification, lipoprotein lipase (LPL), and glycerol-3-phosphate dehydrogenase (GPDH) activity measurements.
Main Results:
- IFN-gamma showed antiproliferative effects, particularly at confluency, and significantly retarded adipoconversion by inhibiting LPL and GPDH activity.
- IL-1 beta slightly enhanced proliferation but also depressed adipoconversion, inhibiting LPL and partially reducing GPDH activity.
- Anti-IFN-gamma antibodies neutralized antiproliferative and anti-LPL effects, with partial neutralization of GPDH inhibition.
Conclusions:
- Both IFN-gamma and IL-1 beta negatively impact adipoconversion in primary rodent preadipocytes.
- Cytokine-induced effects on adipogenesis observed in cell lines are relevant to primary cultures.
- These findings contribute to understanding cytokine regulation of adipose tissue development.