Leptin is a circulating hormone that is secreted primarily by adipose tissue. However, recent studies have demonstrated leptin production by other tissues, including placenta, stomach, kidney, liver and lung, a process not only activated by stimuli such as insulin or corticoids but also hypoxia which is mediated by the hypoxia inducible factor-1. In contrast to this fact, smokers have lower plasma leptin levels. The purpose of this study was to determine whether tissue hypoxygenation (induced by lack of oxygen or inhalation of carbon monoxide, CO) is sufficient to up-regulate leptin in fat cells, as well as in peripheral organs such as lung, liver, and kidney of rats.

In hypoxic rats, leptin expression was unchanged or even reduced in adipose tissue. On the other hand, in liver, kidney and lungs presented we observed an increase in leptin expression when compared with normoxic controls, whereas plasma levels were unchanged. When animals were exposed to CO, generating a functional anemia known to activate the HIF-1-dependent transcription, a significant decrease in leptin gene expression in adipose tissue and in all organs tested was observed. Plasma leptin concentrations after CO exposure were significantly diminished in comparison to control animals.

These findings suggest that tissue hypoxygenation up regulates leptin expression in non-adipose tissue. However, this is not sufficient to raise plasma leptin levels in rats. Inhalation of CO leads to a significant decrease in leptin mRNA and protein concentration in the plasma of the animals, suggesting a negative effect of CO on leptin transcription.