Nitric oxide and downstream second messenger cGMP and cAMP enhance adipogenesis in primary human preadipocytes |
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| Authors: | Karsten Hemmrich Caroline Gummersbach Nora Emilie Paul Daniela Goy Christoph V Suschek Klaus-Dietrich Kröncke Norbert Pallua |
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| Institution: | 1. College of Resources and Environment, Shandong Agricultural University, 61 Daizong Street, Tai''An 271018, China;2. National Engineering Laboratory for Efficient Utilization of Soil and Fertilizer Resources; College of Resources and Environment, Shandong Agricultural University, Tai''An 271018, China;3. Biology 5-Environmental Biology and Chemodynamics, RWTH Aachen University, D-52056 Aachen, Germany;4. Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons, Forschungszentrum Jülich, 52425 Jülich, Germany;5. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, China;6. Institute for Climate and Global Change Research, Nanjing University, Nanjing 210093, China |
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| Abstract: | Background aimsObesity is correlated with chronic low-grade inflammation. Thus the induction of inflammation could be used to stimulate adipose tissue formation in tissue-engineering approaches. As nitric oxide (NO) is a key regulator of inflammation, we investigated the effect of NO and its downstream signaling molecule guanosine 3′,5′-cyclic monophosphate (cGMP) as well as adenosine 3′,5′-cyclic monophosphate (cAMP) on preadipocytes in vitro.MethodsPreadipocytes were isolated from human subcutaneous adipose tissue, cultured until confluence, and differentiated. The NO donor diethylenetriamine (DETA)/NO (30–150 μm) was added during proliferation and differentiation. Additionally, cGMP/cAMP analogs 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP), 8-(4-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphate (8-pCPT-cGMP) and 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP), and the adenylyl cyclase activator forskolin, specific guanylyl cyclase inhibitor 1H-1,2,4]oxadiazolo4,3-a]quinoxalin-1-one (ODQ) and adenylyl cyclase inhibitor 2′-5′-dideoxyadenosine (ddA), were applied. Proliferation and differentiation were evaluated.ResultsDETA/NO in combination with the standard differentiation procedure significantly enhanced maturation of precursor cells to adipocytes. Proliferation, in contrast, was inhibited in the presence of NO. The application of cGMP and cAMP, respectively, increased pre-adipocyte differentiation to an even higher extent than NO. Inhibitors of the underlying pathways caused a significant decrease in adipogenic conversion.ConclusionsOur results support the application of NO donors during transplantation of preadipocytes in a 3-dimensional setting to accelerate and optimize differentiation. The results suggest that, instead of the rather instable and reactive molecule NO, the application of cGMP and cAMP would be even more effective because these substances have a stronger adipogenic effect on preadipocytes and a longer half-life than NO. Also, by applying inhibitors of the underlying pathways, the induced inflammatory condition could be regulated to the desired level. |
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