Targeting oxidative stress in the hypothalamus: the effect of transcription factor STAT3 knockdown on endogenous antioxidants-mediated appetite control.

Abstract

It has been reported that the redox sensing system in the hypothalamus participates in fuel metabolism and that endogenous antioxidants contribute to the regulation of phenylpropanolamine (PPA), an anorectic drug-induced appetite suppression. We explored whether the signal transducer and activator of transcription-3 (STAT3) is involved in PPA's action. Rats were given PPA once a day for 4 days. Changes in endogenous antioxidants, Janus kinase-2 (JAK2), STAT3, neuropeptide Y (NPY), and proopiomelanocortin (POMC), levels during PPA treatment were assessed and compared. Feeding, body weight, and NPY decreased with the biggest reduction on Day 2 during PPA treatment. Antioxidants, JAK2, pSTAT3, POMC expression, and STAT3/DNA-binding activity increased and were expressed in a pattern opposite to NPY expression. Moreover, cerebral STAT3 knockdown modified PPA-induced anorexia and antioxidants, POMC, and NPY expression. superoxide dismutase immunoreactivity in the hypothalamus increased and the inhibition of hypothalamic reactive oxygen species (ROS) production reversed antioxidants, STAT3, POMC, and NPY expression. It is suggested that hypothalamic JAK2-STAT3 participates in regulating antioxidants-mediated appetite control. This result may further the understanding of ROS-involved appetite control.