Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: Implications for leptin's actions

Leptin, the adipocyte-derived hormone, is secreted into the blood and regul ates body weight via its receptors in the hypothalamus. Leptin receptors ar e also present in many peripheral tissues implicating leptin in the regulat ion of other body functions, including reproduction, liver and enteric meta bolism, hematopoiesis, and immunity. Four splice variants of the leptin rec eptor have been identified in humans: the long isoform that has full intrac ellular signaling capacity and 3 shorter isoforms that differ in the length of their cytoplasmic tail. Here, we report the quantification by reverse t ranscriptase-polymerase chain reaction;(RT-PCR) of the relative expression levels of the 2 major leptin receptor splice variants, the long (OB-R-L) an d the shortest membrane bound variant (OB-R-S) in mononuclear cells from pe ripheral blood of 15 healthy human subjects (9 women and 6 men), with a bod y mass index (BMI) that ranged from 19.7 to 41.6. Both OB-R-L and OB-R-S we re coexpressed in all mRNAs tested. However, the expression of the short fo rm (OB-R-S), was on average 8-fold higher than the expression of the long f orm (OB-R-L) (120.8 +/- 12.9 v 14.6 +/- 3.0 relative intensity units, P < . 001). The predominance of the short splice variant over the long one was ap parent in all samples and ranged from 4- to 27-fold. There was no significa nt difference in the expression of either isoform between men and women. Ho wever, the relative expression of both OB-R-S and OB-R-L isoforms was signi ficantly lower in the overweight (BMI > 26), compared with the lean subject s (BMI < 25) (78.8 +/- 9.1 and 6.2 +/- 1.1 v 148.8 +/- 14.4 and 18.9 +/- 4. 0 relative intensity units, respectively, P < .03) and was inversely correl ated with the BMI and plasma leptin levels (P < .01). In conclusion, the ex pression of OB-R-S and OB-R-L leptin receptor isoforms appears to be reduce d in human peripheral blood mononuclear cells from obese individuals, with OB-R-S remaining the predominant leptin receptor isoform. This might have i mplications for the bioavailability and/or action of circulating leptin not only on these cells, but also on other target tissues. Copyright (C) 2000 by W.B. Saunders Company.