Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism.

There is now growing evidence that the reactive oxygen species have an influence on proliferation and antioxidative status of various cell types. The aim of the study was to investigate the effects of different concentrations of leptin, ghrelin, angiotensin II and orexins on proliferation, culture medium malondialdehyde (MDA) levels and antioxidative enzymes activities: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in 3T3 L1 preadipocytes cell culture. Cell proliferation was measured using [(3)H]tymidine incorporation. In 3T3-L1 cells leptin caused a significant reduction in proliferation (by 36%) compared to control. Ghrelin increased preadipocyte proliferation, and the effect was stronger in higher dose (by 39%), while proproliferatory effect of angiotensin II was stronger in lower doses (by 47%). All used doses of orexin A significantly increased 3T3 L1 cell proliferation (from 21% to 160%), while orexin B caused a marked reduction (from 35% to 70%) of this proliferation. The effects of both orexins were dose-dependent. Leptin and ghrelin increased activity of SOD, CAT, GSH-Px and decreased level of MDA. Angiotensin II treatment stimulated only SOD and CAT activities. Influence of orexins was different on various enzymes. Orexin A increased MDA levels, while orexin B caused a marked decrease in MDA levels. Our results strongly suggest the effects of appetite affecting hormones such as leptin and ghrelin on proliferation and antioxidative enzyme activities of preadipocyte cell lines. Orexin A was found to be the most efficient proliferative-signalling hormone, while orexin B revealed the most significant inhibitory effect on preadipocytes proliferation.