Beta-mecaptopethanol suppresses inflammation and induces adipogenic differentiation in 3T3-F442A murine preadipocytes

Thesis (M.A.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Preadipocytes are present in adipose tissues throughout adult life that can proliferate and differentiate into mature adipocytes in response to environmental cues. Abnormal increase in fat cell number or size leads to obesity. It is now recognized that fat cell hypertrophy is a greater risk factor for metabolic syndrome whereas fat tissue that continues to produce newer and smaller fat cells through preadipocyte differentiation is "metabolically healthy". The mechanism that impairs adipogenesis in obesity is still not clear. Because fat cell hypertrophy is often associated with increased oxidant stress and low grade inflammation, both are linked to disturbed cellular redox, we tested how preadipocyte differentiation may be regulated by beta-mecaptoethanol (BME), a pharmacological redox regulator and radical scavenger, using murine 3T3-F442A preadipocytes as the cell model. Effects of BME on adipogenesis were measured by microphotography, real-time PCR, and Western analysis. We provided the proof of principle that preadipocyte differentiation could be regulated by extracellular BME. At an optimal concentration, BME greatly enhanced expression of adipogenic gene markers and lipid accumulation. Using luciferase reporter gene assays, we found that BME had no direct effect on the transcriptional activity of master adipogenic transcription factors, implying that the pro-adipogenic effect of BME is indirect. Consistent with this hypothesis, we show that BME rapidly down-regulated expression of selected inflammatory cytokines, temporally ahead of its inductive effect on adipogenic gene expression. Furthermore, we show that the pro-adipogenic effect of BME was attenuated by TNFalpha, a cytokine known to activate the inflammation cascade and inhibit adipogenesis, in a concentration-dependent manner. These results together suggest that BME induces preadipocyte differentiation through suppression of the endogenous inflammatory pathway