LEPTIN ACTION IN INTESTINAL-CELLS

The adipocyte hormone leptin activates signal transducer and activator of transcription 3 (STAT3) in the hypothalamus, mediating increased s atiety and increased energy expenditure. To date, leptin-mediated acti vation of the STAT pathway in vivo has not been established in tissues other than hypothalamus. We now describe leptin receptor expression a nd in vivo signaling in discrete regions of the mouse gastrointestinal tract. Expression of the functional isoform leptin receptor (OB-Rb) i s restricted to the jejunum and is readily detected by RT-PCR in isola ted enterocytes from this site. Intravenous injection of leptin rapidl y induced nuclear STATE DNA binding activity in jejunum of +/+ and obe se (ob/ob) mice but had no effect in the diabetic (db/db) mouse that l acks the OB-Rb isoform. In addition, an induction of the immediate-ear ly gene c-fos is observed in jejunum in vitro. Leptin-mediated inducti on of a number of immediate-early genes and activation of STAT3 and ST ATE in a human model of small intestine epithelium, CACO-2 cells, corr oborate this effect. Furthermore, intravenous leptin administration ca used a significant a-fold reduction in the apolipoprotein AIV transcri pt levels in jejunum 90 min after a fat load. Our results suggest that the epithelium of jejunum is a direct target of leptin action, and th is activity is dependent on the presence of OB-Rb. Lack of leptin or r esistance to leptin action in this site may contribute to obesity and its related syndromes by directly affecting lipid handling.