Lipopolysaccharide-induced leptin release is neurally controlled

Our hypothesis is that leptin release is controlled neurohormonally. Consci ous, male rats bearing indwelling, external, jugular catheters were injecte d with the test drug or 0.9% NaCl (saline), and blood samples were drawn th ereafter to measure plasma leptin. Anesthesia decreased plasma leptin conce ntrations within 10 min to a minimum at 120 min, followed by a rebound at 3 60 min. Administration (i.v.) of lipopolysaccharide (LPS) increased plasma leptin to almost twice baseline by 120 min, and it remained on a plateau fo r 360 min, accompanied by increased adipocyte leptin mRNA. Anesthesia large ly blunted the LPS-induced leptin release at 120 min. isoproterenol (beta - adrenergic agonist) failed to alter plasma leptin but reduced LPS-induced l eptin release significantly. Propranolol (beta -receptor antagonist) produc ed a significant increase in plasma leptin but had no effect on the respons e to LPS. Phentolamine (alpha -adrenergic receptor blocker) not only increa sed plasma leptin (P < 0.001), but also augmented the LPS-induced increase (P < 0.001). alpha -Bromoergocryptine (dopaminergic-2 receptor agonist) dec reased plasma leptin (P < 0.01) and blunted the LPS-induced rise in plasma leptin release (P < 0.001). We conclude that leptin is at least in part con trolled neurally because anesthesia decreased plasma leptin and blocked its response to LPS. The findings that phentolamine and propranolol increased plasma leptin concentrations suggest that leptin release is inhibited by th e sympathetic nervous system mediated principally by a-adrenergic receptors because phentolamine, but not propranolol, augmented the response to LPS. Because alpha -bromoergocryptine decreased basal and LPS-induced leptin rel ease, dopaminergic neurons may inhibit basal and LPS-induced leptin release by suppression of release of prolactin from the adenohypophysis.