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Contribution of POMC and AgRP neurons to the control of metabolic autonomic nerve activity by leptin
Author(s) -
Bell Balyssa,
Morgan Donald,
Rahmouni Kamal
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1089.2
Subject(s) - leptin , medicine , endocrinology , proopiomelanocortin , leptin receptor , thermogenesis , adipocyte , adipose tissue , brown adipose tissue , arc (geometry) , arcuate nucleus , biology , hypothalamus , obesity , geometry , mathematics
Central action of the adipocyte‐derived hormone leptin is critical for metabolic regulation. Leptin promotes energy expenditure by increasing sympathetic nerve activity (SNA) to thermogenic brown adipose tissue (BAT). Leptin also increases hepatic SNA and parasympathetic nerve activity (PNA) to modulate glucose production by the liver. We previously demonstrated the importance of the hypothalamic arcuate nucleus (ARC) in underlying leptin‐induced increases in BAT SNA as well as liver SNA and PNA, but the contributions of specific neuronal populations within the ARC are not fully understood. Here, we tested the hypothesis that proopiomelanocortin (POMC) and agouti‐related peptide (AgRP) neurons of the ARC mediate regional SNA and PNA responses evoked by leptin. To test this, we used direct multifiber nerve recording to assess the effects of intracerebroventricular (ICV) leptin (2 μg) on regional nerve activity in mice lacking leptin receptors on POMC (POMC Cre /LepR fl/fl ) or AgRP neurons (AgRP Cre /LepR fl/fl ). We observed a partially blunted BAT SNA response to ICV leptin in both POMC Cre /LepR fl/fl (148±29%, p<0.05) and AgRP Cre /LepR fl/fl mice (172±62%, p<0.05) as compared to littermate controls (327±62%), suggesting a distributed control of BAT thermogenesis by leptin across neuronal populations. Conversely, the hepatic SNA response to leptin was significantly reduced in AgRP Cre /LepR fl/fl mice (76±21%, p<0.05), but not in POMC Cre /LepR fl/fl mice (120±49%) relative to controls (196±36%). However, the hepatic parasympathetic response to leptin was completely abolished in mice lacking leptin receptors on either POMC (−17±17%) or AgRP (20±15%) neurons vs control mice (108±24%, p<0.05), indicating that both of these populations are required for leptin to suppress hepatic glucose production. Together, these findings support a critical role for hypothalamic neurocircuitry in dissociating the regional autonomic effects of leptin, in particular with respect to thermogenic control and glucose homeostasis.