Rapid increase in circulating leptin in ventromedial hypothalamus-lesionedrats - Role of hyperinsulinemia and implication for upregulation mechanism

The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions mere investigated. Although rats did not gain bo dy weight or parametrial fat-pad mass 24 h after the operation, the acute V MH-lesioned rats exhibited substantial five- and fourfold increases in plas ma leptin levels compared with sham-operated control rats in fed (22.6 +/- 3.2 vs. 5.8 +/- 1.2 ng/ml) and fasted (8.8 +/- 2.0 vs, 2.3 +/- 0.3 ng/ml) s tates, respectively, Plasma insulin concentration was doubled in VMH-lesion ed rats compared with sham-operated controls in both fed and fasting states . Northern blot analysis revealed that mRNA of ob gene a-as not increased i n parametrial fat pad of animals 24 h after the creation of VMH lesions. He n-ever, leptin content in the fat pad was significantly increased in VMH-le sioned rats compared with sham-operated controls (32.2 +/- 4.7 vs. 17.4 +?- 2.3 ng/g met tissue). The leptin content in parametrial fat pad was highly correlated with plasma leptin concentrations (r = 0.898, P < 0.001), To de fine the effect of hyperinsulinemia on their hyperleptinemia, a small dose of streptozotocin (STZ) (25 mg/kg body wt) was intravenously administered i nto rats 5 days before the creation of VMH lesions. Plasma insulin levels m ere not increased after VMH lesions in STZ-pretreated rats. Plasma leptin l evels mere halved in the absence of hyperinsulinemia, but still remained tw ofold higher than those in their sham-operated counterparts (9.9 +/- 1.3 vs , 4.8 +/- 0.7 ng/ml), These results indicate that the destruction of VMH ra pidly promotes leptin production before obesity develops through an enhance d translational process in which hyperinsulinemia occurring after VMH lesio ning plays an important role. The present study also suggests that there ar e other mechanisms that rapidly upregulate leptin production in adipocytes in VMH-lesioned rats in which the target organ of this hormone has been des troyed.