title: Androgen modulation of pro-inflammatory and anti-inflammatory cytokines during preadipocyte differentiation.
abstract: BACKGROUND
  Macrophages and adipocytes contribute to release of cytokines resulting in the chronic inflammatory profile of the metabolic syndrome. The local increase of proinflammatory cytokines impairs adipogenesis, resulting in formation of dysfunctional adipocytes that are unable to store and handle lipids. The altered lipid fluxes in/from adipocytes affect whole-body metabolism. We investigated the role of androgens on adipocyte-derived proinflammatory and anti-inflammatory cytokines during preadipocyte differentiation.
  
  
  METHODS
  Various differentiation methods were used to obtain full conversion of 3T3-L1 into mature adipocytes. The degree of adipocyte conversion in the presence/absence of dihydrotestosterone (DHT) was analyzed by measuring intracellular triglycerides (Oil Red O staining). The effects of DHT administration on interleukin 1β (IL-1β), IL-2, IL-6, IL-10, IL-12, interferon γ (IFNγ) and tumor necrosis factor α (TNFα) secretion was measured at days 0, 4, 6 and 8 of differentiation using the SearchLight multiplex protein array.
  
  
  RESULTS
  DHT regulates a number of cytokines in committed and mature 3T3-L1 adipocytes. IL-1β and TNFα were readily suppressed at the very early stages of differentiation. IFNγ release was inhibited at day 4, but the effect was no longer detectable on day 8. IL-6 and IL-12 were significantly reduced at day 8 of differentiation. Conversely, the differentiation-dependent increase of IL-2 and IL-10 was further stimulated by DHT since day 0.
  
  
  CONCLUSIONS
  We provide evidence that androgens promote an anti-inflammatory profile that parallels the acquisition of a functional adipocyte phenotype. The crosstalk between androgens, adipocyte-derived mediators of inflammation and intracellular lipid fluxes could have profound implications on metabolism of men with obesity and metabolic syndrome.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pierotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Lolli
authors.forename: Rosa
authors.initials: R
authors.lastname: Lauretta
authors.forename: Chiara
authors.initials: C
authors.lastname: Graziadio
authors.forename: Carla
authors.initials: C
authors.lastname: Di Dato
authors.forename: Emilia
authors.initials: E
authors.lastname: Sbardella
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tarsitano
authors.forename: Aldo
authors.initials: A
authors.lastname: Isidori
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifacio
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Isidori