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Abstract
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INTRODUCTION: Obesity is a chronic low grade inflammatory condition associated with the elaboration of proinflammatory cytokines and adipokines from adipose tissue. Gender dimorphism, (in part due to sex hormones) has been identified after injury and hemorrhagic shock. We hypothesized that the sex hormones estrogen (E2) and testosterone (DHT) have disparate effects on inflammatory mediator production from adipose tissue under stress conditions. This was studied in an in vitro model.
METHODS: Mature adipocytes differentiated from adipose-derived stem cells (ADSC) were co cultured (2:1) with macrophages (RAW 264.7) and subjected to hypoxia-reoxygenation (H/R), and/or incubation with physiologic (10μM) or stress (10μM) concentrations of epinephrine (epi). E2 or DHT were added in a range of physiologic concentrations and culture supernatants were obtained 12 hours post incubation and TNFα, IL-6 and adiponectin levels were measured by ELISA.
RESULTS: Basal TNFα and IL-6 release from co-cultures was significantly increased in response to epi and/or H/R conditions. E2 decreased cytokine release to basal levels, whereas DHT had no effect. Of note, varying the concentration of epi had no effect on cytokine release. Basal levels of adiponectin release were significantly decreased in response to epi and/or H/R conditions. E2 exposure returned adiponectin levels to basal levels, whereas DHT had no effect. The inverse of this relationship was observed in regard to the sex hormones effect on leptin release. E2 returned leptin release to basal levels whereas DHT had no effect.
CONCLUSION: Stress levels of epi and H/R increased proinflammatory cytokine production and decreased adiponectin levels in adipocyte co cultures. E2 at physiologic concentrations decreased TNFα, IL-6 and preserved adiponectin levels following Epi and/or H/R conditions. There was no effect of DHT on mitigating the proinflammatory response. Our results suggest a gender dimorphism in adipose tissue under stress conditions that may explain the conflicting data in the literature.
Language: en |