Abstract
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 adipocyte number or size leads to fat tissue expansion. However, it is now recognized that adipocyte 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”. Because adipocyte 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-mercaptoethanol (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. Our data demonstrated that preadipocyte differentiation could be regulated by extracellular BME. At an optimal concentration, BME enhanced expression of adipogenic gene markers and lipid accumulation. This effect was associated with BME-mediated down-regulation of inflammatory cytokine expression during early differentiation. BME also attenuated TNFalpha-induced activation of NFkappaB in differentiating preadipocytes and partially restored TNFalpha-mediated suppression on adipogenesis. Using a non-adipogenic HEK293 cell line transfected with luciferase reporter genes, we demonstrated that BME reduced basal and TNFalpha-induced NFkappaB activity and increased basal and ciglitazone-induced PPARgamma activity; both may contribute to the pro-adipogenic effect of BME in differentiating F442A preadipocytes.
Highlights
Impaired fat storage capacity in adipose tissue is implicated in the pathogenesis of obesity-related diseases
Recent literature shows that drug-mediated inhibition of adipogenesis in mice on a high-fat diet results in significantly reduced weight gain and subcutaneous and gonadal fat mass but this effect was associated with marked adipocyte hypotrophy, enhanced macrophage infiltration, and apoptosis [2]
Treatment with BME did not increase the C/EBP-driven luciferase activity in HEK293 cells. These results suggest that BME directly modulate transcriptional activity of PPARgamma that may contribute to its pro-adipogenic effect
Summary
Impaired fat storage capacity in adipose tissue is implicated in the pathogenesis of obesity-related diseases. Compared to obese subjects with metabolic syndrome, metabolically healthy obese subjects have been shown to possess greater adipogenic activity and reduced inflammation [3]. For this reason, it has been suggested that in the setting of obesity, an enhanced adipogenic capacity of fat tissue could be protective against other metabolic diseases [4]. Based on the large body of literature showing increased oxidant stress in fat tissue of obese animals and humans [8,9], one would expect that an increase of antioxidants in the cells may help to curb inflammation and improve fat tissue function, including restoration of active adipogenesis. Some studies have reported that selected antioxidants enhance adipogenesis [10], others reported controversial findings [11,12,13,14]
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