Regulation of sympathetic nerve activity by l-carnosine in mammalian white adipose tissue

Previously, we showed that l-carnosine, a bioactive dipeptide, influences the sympathetic nerve activity innervating kidney and brown adipose tissue. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of l-carnosine on the sympathetic nerve activity innervating white adipose tissue (SNA-WAT) and lipolysis. We found that intraperitoneal (ip) administration of l-carnosine at doses of 100 ng/rat and 10 μg/rat elevated and suppressed SNA-WAT, respectively. The effect of lower dose of l-carnosine (100 ng/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H1 receptor antagonist. In contrast, the effect of higher dose of l-carnosine (10 μg/rat) was suppressed by thioperamide maleate salt, a histamine H3 receptor antagonist. Moreover, ip administration of 100 ng and 10 μg of l-carnosine increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The changes of plasma FFAs resulting from the exposure to 100 ng and 10 μg of l-carnosine were diminished by the β-adrenergic receptor blocker propranolol hydrochloride and the muscarinic receptor blocker atropine sulfate, respectively; and eliminated by the corresponding histamine receptor antagonists, which eliminated the changes in SNA-WAT. Our results suggest that low doses of l-carnosine may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H1 receptor, and that the β3-receptor may be involved in this enhanced lipolytic response. High doses of l-carnosine, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H3 receptor, and the muscarinic receptor may be related to this response.